Cagnie, Barbara

Cambier, Dirk

Vinck, Elke

VINCK, H

English

Ghent University Academic Bibliography

PHOTODYNAMIC THERAPY OF FELINE SUPERFICIAL SQUAMOUS CELLCARCINOMA OF THE NASAL PLANUMDe fotodynamische behandeling van een oppervlakkig plaveiselcelcarcinoomvan de neusspiegel bij een katE. Vinck1, H. Vinck2, B. Cagnie1,  D. Cambier11 Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences,Ghent University, University Hospital, De Pintelaan 185 (6K3), 9000 Gent, Belgium2 Dendermondesteenweg 624, 9070 Destelbergen, Belgiumelke.vinck@UGent.beABSTRACTThe objective of this case report was to demonstrate the feasibility of photodynamic therapy for thetreatment of feline superficial squamous cell carcinoma and to illustrate its approachability in veterinarianpractice.Photodynamic therapy using topical 5-aminolaevulinic acid was applied on a superficial squamous cellcarcinoma at the nasal planum of a cat. After applying of the cream, the irradiation was performed with ared Light Emitting Diode contrivance with a wavelength of 660 nm. The following day, the tumour area was erythematous and oedematous. On the second day after thetreatment a scab was formed. The response rate was encouraging as visual observation of the tumour arearevealed a removal of the malignant cells. The recovery of the normal epithelialised skin structure wasobserved two months after the treatment. A follow-up period up to two years revealed no recurrence.These promising results demonstrate that photodynamic therapy should be considered as treatmentmodality for early stage superficial squamous cell carcinoma. SAMENVATTINGAan de hand van deze casus tracht men de bruikbaarheid van fotodynamische behandeling voor eenoppervlakkig plaveiselcelcarcinoom bij een kat te illustreren en deze toegankelijk te maken voor de toepassing inde diergeneeskundige praktijk.Een plaveiselcelcarcinoom ter hoogte van de overgang van de neusspiegel en de neusrug bij een kat werdfotodynamisch behandeld door middel van 5-aminolevulinezuurzalf in combinatie met bestraling door middel van een toestel met rode licht emitterende dioden, met een golflengte van 660 nm.Daags na de fotodynamische behandeling vertoonde de behandelde zone erytheem en oedeem, de tweede dagna de bestraling werd korstvorming vastgesteld. De uiteindelijke reactie van het weefsel op de behandeling wasgunstig; tijdens visuele observaties twee maanden na de behandeling werden geen maligne cellen meer vastgesteld en vond men normaal huidepitheel op de locatie van de laesie.Er werd in de loop van de twee jaar durende follow-up periode geen recidief vastgesteld. Deze veelbelovende resultaten laten toe te concluderen dat fotodynamische behandeling bij oppervlakkigeplaveiselcelcarcinomen overwogen dient te worden.INTRODUCTIONIn clinical practice, feline squamous cell carci -noma (SCC) of the skin is traditionally treated bysurgery, cryosurgery, intralesional chemotherapyand/or radiotherapy (Lana et al. , 1997; Moore andOgilvie, 2001). Though the success ratios of thesetreatments are relatively high, they do involve anumber of disadvantages. These forms of therapy arecostly and potentially harmful. They can leave a scar424               Practical note Vlaams Diergeneeskundig Tijdschrift, 2004, 73, 424-428and hypo- or hyperpigmentation, and may have otherside effects such as pain, severe inflammation andirritation (De Rosa and Bentley, 2000; Moore andOgilvie, 2001).The search for a more acceptable treatment that iscapable of killing cancerous cells in a more selectiveway has led to the development of photodynamictherapy (PDT). PDT is a treatment modality based onthe interaction between a photosensitizer (precursor), light and oxygen, which causes photochemically in -du ced selective cell death (De Rosa and Bentley,2000; Guillen et al. , 2000; Maier et al. , 2001; Mortonet al. , 2002). The selective toxicity of PDT is based on the preferential uptake or retention of the photo -sensitive agent at higher concentrations in tumortissue than in the surrounding normal tissue. Appli -cation of the photosensitizer is followed by exposureto light of a wavelength corresponding to one of theabsorption maxima of the photosensitizer. Light ab -sorption transforms the sensitizing agent from itsground state into an excited triplet state molecule. The excited triplet can undergo two types of reaction. Itcan transfer its energy to oxygen directly to formreactive singlet oxygen. Alternatively, it can transferits energy to intermediate molecules, which then react with oxygen to produce free radicals. As a result of the activation of reactive singlet oxygen or free radicalproduction, subsequent tissue damage is generated.Without exposure of the photosensitizer to light of the appropriate wavelength, the photosensitizer is notactivated and so there is no effect on the tumor tissue(Cairnduff et al. , 1994; Lucroy et al. , 2000; Lucroy etal.  2002; Morton et al. , 2002; Peng et al., 1997; Stell etal., 2001). This case report, which is aimed at fami -liarizing practitioners with the use of PDT and providing the necessary information for eventual clinical appli -cation, deals with recent clinical pro gress in topical PDT of skin cancer using 5-amino laevulinic acid (5-ALA)and Light Emitting Diodes (LEDs). MATERIALS AND METHODSA neutered male cat (domestic longhair, 18months, 4 kg, FeLV negative and FIV negative) withcytologically confirmed superficial SCC of the nasalplanum and the transition to the bridge of the nose,and tumor grade T1 (Figure 1) (Owen, 1980; Hahnand Richardson, 1995; Moore and Ogilvie, 2001) wasselected for photodynamic treatment with 5-ALA and LED. Macroscopically, a grade T1 tumor (Owen,1980; Hahn and Richardson, 1995; Moore and Ogil -vie, 2001) is characterized by a crusting lesion witherythemic tissue beneath the crust. According to theTNM classification system, a T1 tumor is superficialand non-invasive (Owen, 1980; Hahn and Richard -son, 1995; Moore and Ogilvie, 2001). Figure 2 pic -tures the corresponding cytological appearance. Thediameter of the lesion (Figure 1) was approximately1.2 cm. Clinical and routine blood examinations con -firmed the good general health of the cat and nopalpable regional lymph node enlargements weredetected. Sensitization with 5-ALA cream was prece -ded by cleaning of the SCC with sterile poly vi don- iodine 10% solution (iso-BETADINE; Asta Medica)and removal of the crust. Two millimeters of Porphin5-ALA cream 20% (Aladerm; Crawford Pharma -ceuticals) was applied topically to the lesion and to a2 mm margin of apparently normal skin tissue. Appli -cation occurred by means of a cotton swab. The cream was applied over a period of five hours. Every 30minutes the presence of the cream was examined and,if necessary, more cream was applied. The cat wasanesthetized throughout the entire procedure to avoidattempts to remove the cream by licking or rubbingand to avoid discomfort. Sedation was done withMedetomidine HCl 1 mg/ml (Domitor, Pfizer AnimalHealth) at 0.05 mg/kg intramuscular and anesthesiawith Ketamine HCl 100 mg/ml (Anesketin, Eurovet)at 2.5 mg/kg intramuscular. Propofol 10 mg/ml (Rapi -novet, Schering-Plough), which served as mainte -nance anesthesia, was administrated intravenously asneeded throughout the procedure. An insulant wasused to prevent hypothermia during anesthesia. Afterremoval of the photosensitizing agent, irradiationwas accomplished using a red Light Emitting Diodecontrivance (BIO-DIO preprototype; MDB-LaserBel gium) with a wavelength of 660 nm. LED irra -diation at continuous mode was administered for aperiod of 20 minutes at a power output of 80 mW,resulting in a radiant exposure of 38 J/cm2. Duringirradiation, the distance from light source to treatment area was 0.6 cm and aluminized tape was used toprotect the eyes of the cat from irradiation (Figure 3).Immediately before irradiation, the tumor area wasexposed to the ultraviolet light of a Wood lamp,verifying the presence of the typical red fluorescentspectrum of protoporphyrin IX (PPIX).RESULTSBesides normal distress after anesthesia, no ad -verse effects were monitored during a hospitalizationVlaams Diergeneeskundig Tijdschrift, 2004, 73 425of 48 hours following the treatment. Consequently,no local anesthesia was administrated, though as aprecautionary measure an Elizabethan collar wasapplied for 24 hours to prevent licking, rubbing andscratching. The day following irradiation, the tumor area be -came erythematous and somewhat edematous. Thecat did not attempt to lick or scratch the treated area.Two days after the treatment, a scab developed. Res -ponse to the therapy was assessed by visual obser -vation of the tumor area at 1 month (Figure 4),2 months, 6 months and 2 years post-treatment. Thesecond observation, at two months post-treatment,revealed a complete response, which is defined as thedisappearance of the malignant cells (based on ma -cro scopic observations) and the complete dis ap pear -ance of the crusting lesion, which relates to the reco -very of normal re-epithelialized skin structure. Norecurrence was noted up to two years post-treatment.  DISCUSSIONIn the perspective of this case, PDT using topical5-ALA and LED can be considered as safe and effec -tive in treating early stage SCC of the skin. The initialresponse rate was encouraging, as normal tissue was426 Vlaams Diergeneeskundig Tijdschrift, 2004, 73Figure 1. The tumour area after cleaning and remo -ving the crust, immediately before photodynamicaltherapy with 5-aminolaevulinic acid and red LightEmitting Diodes.Figure 4. Response at the time of the first visualobservation, one month after the photodynamicaltherapy with 5-aminolaevulinic acid and red LightEmitting Diodes. The tumour is cleared from thenasal planum, the crusting lesion has disappearedand normal epithelia is emerging.Figure 2. Cytological appearance of a tumour gradeT1 (Owen, 1980; Hahn and Richardson, 1995;Moore and Ogilvie, 2001). Figure 3. Irradiation of the SCC using a red LightEmitting Diode contrivance (BIO-DIO preproto -type; MDB-Laser Belgium) with a wavelength of 660nm. The eyes of the cat were protected from irra -diation with aluminised tape.spared and healing occurred very fast.  There also wasan excellent cosmetic result, thanks to the smallamount of crust formation. In accordance with somestudies (Reeds et al. , 2004) and in contradiction toothers (Peaston et al. , 1993; Frimberger et al., 1998;Stell et al. , 2001; Touma et al., 2004), this study didnot reveal adverse effects such as local discomfort,lack of appetite or vomiting. Thanks to the topical useof the cream, systemic effects and generalized photo -sensitization leading to cutaneous sensitivity, whichhas been noted in cases of intravenously administered  photosensitizing agent (Hahn et al., 1998), was ab -sent and the cat could be exposed to sunlight within 24 hours after the treatment (Savary et al. , 1998; Maieret al., 2001).Apart from the convincing outcome, several points should be noted. First of all it should be noted thatduring the follow up period the cat was exposed tonearly no direct sunlight as the owners live in anapartment. As sun avoidance and protection fromsunlight are important precautionary measures toprevent recurrence of superficial squamous cell carci -nomas, one essential risk factor for possible recur -rence was eliminated (Anonymous, 2003; Alam andRatner, 2001; Moore and Ogilvie, 2001). Se condly,the lesion was rather superficial (T1)(Owen, 1980;Hahn and Richardson, 1995; Moore and Ogil vie,2001) and, as Peaston et al. (Peaston et al., 1993)state, treatment is more effective in tumors at stage T2and earlier. A third and final remark relates to the factthat only one case, and hence one type of lesion, wasconsidered at one specific location. Consequently, the extrapolation of  the results to various types oftumors, tumors located elsewhere than the nasal pla -num, and tumors with deeper dermal involvement(stages T2-T4) (Owen, 1980; Hahn and Richardson,1995; Moore and Ogilvie, 2001) is only permittedafter the treatment of a large number of variousdifferent tumors at different stages and at variousdifferent locations in the body. The above mentioned points, which provide amplematerial for future investigations, do not lower theconsiderable value of this study, which has provedthat PDT can lead to beneficial results in the treatment of superficial SCC of the nasal planum in cats. Since this innovative procedure is a valuable alter -native to conventional treatment (Reeds et al., 2004),it is necessary to inform practitioners about it and tofamiliarize them with the use of PDT. By drawing upan elaborate description of the materials and methods, the investigators have endeavored to make the proce -dure accessible for daily veterinarian practice, or atleast to encourage veterinarians to refer patients tocolleagues where PDT is available. ACKNOWLEDGEMENTSThe authors are greatly indebted to Ms. T. Van denBerghe for her assistance both during treatment andduring the follow up phase while the cat was still in the hospital. Thanks also to Prof. Dr. J. Declercq forsupplying the necessary cytological photograph of asquamous cell carcinoma.REFERENCESAlam, M., & Ratner, D. (2001). Cutaneous squamous-cellcarcinoma. The New England Journal of Medicine 344(13), 975-983.Anonymous (2003). Squamous cell carcinoma. CurrentPro blems in Dermatology-US 3, 91-133.Cairnduff, F. Stringer, M., Hudson, E., Ash, D. & Brown S.(1994). Superficial photodynamic therapy with topical5-aminolaevulinc acid for super ficial primary andsecon dary skin cancer. British Journal of Cancer 69,605-608.De Rosa, F.S & Bentley, V.L.B. (2000). PhotodynamicThe ra py of skin cancers: sensitizers, clinical studiesand future directives. Pharmaceutical Research 17(12), 1447-1455.Frimberger, A., Moore, A., Cincotta L., Cotter, S., & FoleyJ. (1998). Photodynamic therapy of naturally occurringtumors in animals using a novel benzophenothiazinepho to sensitizer. Clinical Cancer Research 4, 2207-2218.Guillen, C., Sanmartin, O., Escudero, A., Botella-Estrada,R., Sevila, A. & Castejon, P. (2000). Photodynamic the -ra py for in situ squamous cell carcinoma on chronic ra -dia tion dermatitis after photosensitization with 5-ami -nolaevulinic acid. Journal of the European Academy ofDermatology and Venereology 14, 298-300.Hahn, K., Panjehpour, M., & Legendre A. (1998). Photo -dynamic therapy response in cats with cutaneous squa -mous cell carcinoma as a function of fluence. Veteri -nary Dermatology 9, 3-7.Hahn, K. & Richardson, R. (1995). The basics of cancerchemotherapy. Clinical Staging: Staging Classi -fications. In: Hahn, K. & Richardson, R. (eds.). CancerChemotherapy. A Veterinary Handbook. Williams &Wilkins, USA, pp. 25-42.Lana, E., Ogilvie, G., Withrow, S., Straw, R., & Rogers, K.(1997). Feline cutaneous squamous cell carcinoma ofthe nasal planum and the pinnae: 62 pinnae. Journal ofthe American Animal Hospital Association 33, 329-332.Lucroy, M. (2002). Photodynamic therapy for companionanimals with cancer. The Veterinary Clinics. Small Ani -mal Practice 32, 693-702.Vlaams Diergeneeskundig Tijdschrift, 2004, 73 427Lucroy, M., Edwards, B., & Madewell, B. (2000). Vete ri -nary photodynamic therapy. Journal of the Ame ricanVete ri nary Medical Association 216, 1745-1751.Maier, A., Tomaselli, F., Matzi V. Rehak, P., Pinter, H. &Smolle-Jüttner, F. (2001). Photosensitization with he -ma toporphyrin derivative compared to 5-amino laevu -linic acid for photodynamic therapy of esophagealcarcinoma. Annals of Thoracic Surgery 72, 1136-1140.Morton, C., Brown, S., Collins, S., Ibbotson, S., Jen kin -son, H., Kurwa, H., Langmack, K., McKenna, K.,Mose ley, H., Pearse, A.D., Stringer, M., Taylor, D.K.,Wong, G. & Rhodes, L.E. (2002). Guidelines for topicalphotodynamic therapy: report of a workshop of theBritish Photodermatology group. British Journal ofDer matology 146, 552-567.Moore, A. & Ogilvie, G. (2001). Management of specificdiseases. Skin tumors: Squamous cell carcinoma. In:Ogilvie, G. & Moore, A. (eds.). Feline Oncology. Acom prehensive guide to compassionate care. Vete ri -nary Learning Systems, USA, pp.412-418 .Owen, L. (1980). TNM Classification of Tumors inDomestic Animals. Geneva, World Health Orga nisa -tion, pp. 46-47.Peaston, A., Leach, M. & Higgins R. (1993). Pho to dy na -mic therapy for nasal and aural squamous cell carci -noma in cats. Journal of the American Veteri nary Medi -cal Association 202(8), 1261-1265.Peng, Q., Warloe, T., Berg, K., Moan, J., Kongshaug, M.,Giercksky, K-E. & Nesland, J. (1997). Cancer 79(12),2282-2308.Reeds, K., Ridgway, T., Higbee, R. & Lucroy, M. (2004).Veterinary and Comparative Oncology 2(3), 157-163.Savary, J.-F., Grosjean, P., Monnier, P., Fontolliet, C.,Wagnieres, G., Braichotte, D. & van den Bergh, H.(1998). Photodynamic therapy of early squamous cellcar ci nomas of the oesophagus: A review of 31 cases.Endoscopy 30, 258-265Stell A., Dobson, J., & Langmack, K. (2001). Photo dy na -mic therapy of feline superficial squamous cell carci -noma using topical 5-aminolaevulinc acid. Jour nal ofSmall Animal Practice 42, 164-169.Touma, D., Yaar, M., Whitehead, S., Konnikov, N. &Gilchrest, B. (2004). A trial of short incubation, broad- area photodynamic therapy for facial actinic keratosesand diffuse photodamage. Archives of Dermatology140, 33-40.428 Vlaams Diergeneeskundig Tijdschrift, 2004, 73

Photodynamic therapy of feline superficial squamous cell carcinoma of the nasal planum

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Photodynamic therapy of feline superficial squamous cell carcinoma of the nasal planum

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