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The results of CO2 laser surgery in patients with oral leukoplakia: a 25 year follow up
Oral Oncology (2005) 41, 31–37
http://intl.elsevierhealth.com/journals/oron/
The results of CO2 laser surgery in patients with oral leukoplakia: a 25 year follow up P.S. van der Hem*, J.M. Nauta, J.E. van der Wal, J.L.N. Roodenburg Department of Oral and Maxillofacial Surgery, Groningen University Hospital, P.O. Box 30001, 9700 RB Groningen, The Netherlands Received 29 April 2004; accepted 3 June 2004
KEYWORDS
Summary Oral leukoplakia is an important premalignant lesion of the oral mucosa. We treat this lesion prophylactically with CO2 laser evaporation. In the period from 1976 to 2001, a group of 200 patients with 282 oral leukoplakias were treated by CO2 laser evaporation. In a follow up period of 1–219 months (mean 52), 251 treated leukoplakias (89.0%) did not show a recurrence. Twenty eight (9.9%) local recurrences were observed in 5 to 168 months after treatment. Three (1.1%) squamous cell carcinoma, occurred in the treated area respectively 7, 17 and 19 month after CO2 laser evaporation. This large study with a long follow up shows that laser treatment is a good prophylactic treatment for oral leukoplakia. c 2004 Elsevier Ltd. All rights reserved.
Oral leukoplakia; Carbon dioxide laser surgery; Recurrence; Epithelial dysplasia; Malignant transformation
Introduction Oral leukoplakia is a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion; some oral leukoplakias will transform into cancer.1 Histologically, leukoplakia is an intraepithelial lesion consisting of epithelial hyperplasia, with or without hyperkeratosis and minimal inflammation, and with or without varying degrees of dysplasia. As stated, oral leukoplakia can transform into a malignant lesion. According to the literature the * Corresponding author. Tel.: +31 50 361 2567; fax: +31 50 361 1136. E-mail address: [email protected] (P.S. van der Hem).
overall chance of malignant transformation varies from 0.13% to 17.5%.2 This is related to the clinical and histological classification and the location of the lesion. Lesions that are at high risk are clinical nonhomogeneous (verrucous and erosive) types, lesions with histologically epithelial dysplasia and the lesions that are located on the borders of the tongue and floor of mouth.2,3 Factors associated with an increased risk of malignant transformation are the gender (female); duration (years); idiopathy of the lesions, and presence of Candida albicans.4–13 Conventional types of treatment have been excision by scalpel, and cryosurgery. The recurrence rate varies for excision from 10% to 34%4–6 and for cryosurgery from 12% to 25%14–17 according to literature. These modalities cause scarring, contraction and can mask early signs of recurrence.2,18
1368-8375/$ - see front matter c 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2004.06.010
32
P.S. van der Hem et al. Table 1 Age and sex distribution of 200 patients with an oral leukoplakia n
Age (yr)
Mean (yr)
Men Women
109 91
30–79 33–86
56.5 67.5
Total
200
30–86
59.5
Table 2 patients
Localization of 282 oral leukoplakias in 200
Location
Figure 1 scanner.
The Sharplan 40C CO2 laser with a Surgitouch
Since 1970s, studies have shown that the CO2 laser (Fig. 1) is an effective instrument for the treatment of premalignant lesions of the oral mucosa. Soft tissues can be superficially removed by evaporation with minimal thermal damage to adjacent tissue, which results in minimal tendency to scar and little postoperative pain and edema.19–21 Using a CO2 laser, selective removal of epithelium can be performed. Therefore this modality is very suitable for the treatment of intraepithelial lesions like oral leukoplakia.22,25–28 The aim of this study was to look at the recurrence rate and degeneration into malignancy in a large group of patients with oral leukoplakia, after treatment with CO2 laser surgery with a long period of follow up. In this study we use cases who were already used in the evaluation of 1991.2
n
Upper lip Lower lip Labial commissure Buccal mucosa Floor of mouth Tongue Palate Gingiva Anterior tonsillar pillar
4 21 21 58 55 64 10 36 13
Total
Table 3
282
% 1.4 7.5 7.5 20.6 19.5 22.7 3.6 12.6 4.6 100
Size of 282 oral leukoplakias in 200 patients
Size (cm) \2 2.4 [4 Total UnKnown
n
%
45 78 10
33.8 58.7 7.5
133 149
100
the lesions was classified as less than 2 cm, 2–4 cm, and more than 4 cm (Table 3). The tongue, buccal mucosa and floor of mouth were the areas most frequently affected (Table 2). According to the clinical classification, 136 (69%) homogeneous
Material and methods Leukoplakia In the period from 1976 to 2001, 200 patients with 282 oral leukoplakias were treated by CO2 laser evaporation. This group was followed until 2001. The sex and age distribution is given in Table 1. Of these 200 patients, 62 (31%) had been treated previously for a squamous cell carcinoma of the oral mucosa. In 68 patients, there was multifocal leukoplakia. The frequency of the lesions in the several locations is shown in Table 2. The size of
Table 4 Histology of the primary lesion in 200 patients with an oral leukoplakia Dysplasia
n
No Little Moderate Severe Squamous cell carcinoma
152 47 28 12 3
Total
242
% 62.8 19.4 11.6 5.0 1.2 100
Results of CO2 laser surgery in patients with oral leukoplakia and 61 (31%) nonhomogeneous leukoplakias were treated. The group of nonhomogeneous lesions was divided into 31 (16%) verrucous and 30 (15%) erosive leukoplakias. The histology of the lesions is shown in Table 4.
Laser equipment In the period from 1976 to 2001, oral leukoplakia was treated by evaporation with a CO2 laser. The first 17 treatments were performed with the handpiece, later, a micromanipulator together with an operation microscope (Zeiss Opmi 1) (Fig. 2) was used. During this period several CO2 laser systems were used with the same physical characteristics. These systems were respectively the Sharplan 791, the Cavitron and the Sharplan 40C. Because the CO2 laser produces a straight light beam, not every location in the mouth can be reached. Therefore we developed an endoscope (Fig. 3) with a 45°
33
stainless steel mirror that was coupled to the micromanipulator. With this equipment all sides of the oral cavity could be treated.
Patient management Patients with an oral leukoplakia (Fig. 4a) received a complete physical head and neck examination. The lesion was classified according to possible cause, location, clinical appearance, and gender and age of the patient. For histologic classification one or more incisional biopsies were taken under local anesthesia. If possible, etiologic factors were eliminated. Almost all treatments (96%) were carried out with the patient under local anesthesia on an outpatient basis. General anesthesia was necessary only for treating locations
Figure 2 The micromanipulator together with the operation microscope (Zeiss Opmi 1).
Figure 3 The endoscope with a 45° stainless steel mirror coupled to the micromanipulator.
Figure 4 (a) A patient with erosive leukoplakia with severe dysplasia in the floor of mouth and the ventral side of the tongue. (b) The situation directly after CO2 laser evaporation. (c) Wound healing four weeks after CO2 laser evaporation.
34 that were otherwise not accessible, such as the soft palate. In the case of general anesthesia the endotracheal tube was covered with a reflective metal tape to prevent accidental perforation by the laser beam. Nowadays endotracheal laser tubes are available. The use of explosive gasses should be avoided. We preferred an operation microscope and micromanipulator to perform the treatment. This gives the advantage of optical magnification and a stable system to aim the laser beam at the area to treat, resulting in an excellent control over the procedure. The treatment was carried out by moving a slightly defocused CO2 laser spot of about 1 mm over the lesion until it was completely evaporated and the submucosa was reached (Fig. 4b). A margin of about 3 mm around each lesion was taken. Output powers of 15–20 W were used, and defocusing of the beam was achieved by elevating the focus of the handpieces a few millimeters above the tissue surface, or by a adjustable lens in the micromanipulator. The Sharplan 40C was used with a scanning device (Surgitouch) connected with the operation microscope. With the scanning device it was possible to use the laser beam in focus and to reduce carbonization. Small lesions were treated in one session; larger lesions took two or more treatments. For postoperative care a 0.1% chlorhexidine mouthwash and paracetamol analgesic were prescribed. In case of lesions of the vermillion border of the lip vaseline was used for wound care. After treatment, the patients were seen for follow up after 4 weeks, 3 months, and 6 months, and were subsequently followed up on a yearly basis during the whole period. A local recurrence was defined as a leukoplakia arising within the borders of the treated area.
Results Wound healing took place by epithelization from the border of the wound. In almost all cases this healing was complete within 4 weeks (Fig. 4c). After healing, there was almost no clinically perceptible difference in appearance or elastic properties of the laser-treated mucosa to normal mucosa. In a mean follow up period of 52 months range (1–219 months), 251 treated leukoplakias (89.0%) did not show a recurrence. The follow up of 15 lesions was ended because of interrecurrent death, in 49 cases because the patient moved and was lost to follow up or the follow up was carried out by the dentist or in another hospital. These cases were excluded from the study. In 13% of the recurrence-free cases a biopsy was taken, which confirmed the clinical result. In the
P.S. van der Hem et al. group of 282 treated leukoplakias, 28 (9.9%) local recurrences were observed. These recurrences occurred in a mean period of 87 months (5–168) after treatment and were confirmed by biopsy. In four of the 28 cases, the recurrences showed higher degree of dysplasia than in the earlier treated lesion. There were 3 (1.1%) cases in which a squamous cell carcinoma occurred, respectively 7, 17 and 19 month after treatment. There was no relationship to the clinical or histologic classification of the treated lesion and the appearance of a recurrence. Table 4 shows the histology of all the primary lesions which were biopsied. All 28 recurrences in the leukoplakia group, were retreated by CO2 laser evaporation and 27 of these recurrences were recurrence free after one to four retreatments. One patient was not recurrence free even after another three retreatments. Of the recurrences 18 occurred in male patients and 10 in female patients. Of the 28 recurrences, there were 12 smokers. Thirteen of these leukoplakias were localized on tongue cq floor of mouth. Of the recurrences that were biopsied two showed histologically moderate and one severe dysplasia. Twenty-three of the recurrences were homogenous, two were verrucous and three erosive. Twelve (43%) recurrences developed within three months, five (18%) within six month, nine (32%) within one year and two (7%) after one year. From the 28 recurrences, there were eight multifocal leukoplakias (29%). There were 14 (50%) patients with an oral tumor in the past. From the cases which showed malignant transformation, initial biopsies showed in one case severe dysplasia and no dysplasia in two cases. Two were localized at the floor of mouth and one at the tongue. There were two males and one woman. Two of them were smokers, one man and one woman. Clinically there were two homogeneous and one erosive lesion.
Discussion In comparing our present results with the evaluation of 1991 we see a comparable recurrence rate. In 1991, 70 patients with 103 lesions were treated, with a mean follow up of 5.3 years (0.5–12). There were 10 recurrences which is 10% (Table 5), 7–55 month after treatment. No transformation into squamous cell carcinoma was seen. From the 10 recurrences, 4 were treated again and did not show recurrence. In our present study we have treated 200 patients with 282 lesions with a mean follow
Results of CO2 laser treatment in oral leukoplakia in the literature
Treatment
Author (yr)
n
Cured
n Surgery Cryosurgery
CO2 laser evaporation or excision
Recurrence
Squamous carcinoma cell
%
n
%
n
Vedtofte (1987) Silverman (1984)
61 61
40
66
20 21
34
5 0
Sako (1972) Bekke (1979) Gongloff (1980)
69 24 15
48 18 13
80 75 87
8 3 8
13 12 13
4 0 0
93
90
10 10 4 6 21
10.8 10
0
Silverman (1988) Roodenburg (1991) Gerlach (1993) White (1998) CO2 YAG Schoelch (1999) YAG Thomson (2002) Ishii (2003) Present study
38 103 233 17 22 55 57 82 282
45 58 254
89.0
12 24 28
Mean
% 1.0–5.0 yr 7.2 yr 7
2.6
23.5 27.2 38.1 24 29.3 9.9
Follow up
2.5–4.5 yr 0.1–5.2 yr 0.7–4.4 yr 3–10 yr 6–144 month 0–3.8 yr
2.5 yr 2.2 yr 5 yr
Results of CO2 laser surgery in patients with oral leukoplakia
Table 5
6–178 month 4 1 3
7 1.2 1.1
1–44 month
18 month
1–219 month
35
36 up of 4.3 years (1–219 months). There were 28 recurrences which is 9.9%, 5–168 month after treatment. Twenty-seven lesions were recurrence-free after 1–4 retreatments. However three cases (1.1%) showed malignant transformation after 7, 17 and 19 month. The initial biopsies showed severe dysplasia (1 case) and no dysplasia (2 cases). Early malignant transformation can be explained by a sampling error of the incisional biopsy. When small biopsy specimens are taken, there is a chance of missing an area of malignancy. Therefore, the biopsy specimens must be taken from the most suspicious area such as erosions or verrucous changes. Large lesions require more than one biopsy. Two of the squamous cell carcinomas were localized in the floor of mouth and one at the border of the tongue. There were two women and one man. Two were smokers, one man and one woman. Two of the leukoplakias were homogenous and one erosive. Histologically there was initially one severe dysplasia and two showed no dysplasia. Except for etiologic factors, there was no correlation between the several classifications of the leukoplakia and the development of a recurrence or squamous cell carcinoma. Due to excellent wound healing after CO2 laser evaporation, a squamous cell carcinoma can easily be recognized by clinical evaluation. Therefore, careful follow up is mandatory after treatment. The cure rate of 89.0% in our study of CO2 lasertreated leukoplakias is remarkably high as compared to other studies (Table 5).2,4,6,11,14–16,22–24,29 When one looks at the results of excision this can be explained by a remaining etiologic factor, however in our study 16 recurrences (57%) were nonsmokers. Etiologic factors might play a role in the difference in cure rate in case of cryosurgery. An important difference between cryosurgery and laser treatment is that with CO2 laser the effect can be directly observed. With cryosurgery the tissue is rejected afterwards as necrosis, so the depth of the treatment is not as well controlled as compared with the CO2 laser evaporation in combination with an operation microscope. Comparing our present results with the evaluation of 1991 there is a small increase in the cure rate in a much longer follow up period. So within a long period of time we did not see a significant increase in the amount of recurrences. The lower cure rate of former studies by others may be caused by the technique. Some studies performed the treatments with a handpiece, whereas we used the micromanipulator and operation microscope in 81% of the treatments. By using the operation microscope, there is a better control of the treatment.
P.S. van der Hem et al.
Conclusions With excision, cryosurgery and CO2 laser evaporation for the treatment of oral leukoplakia, good cure rates can be obtained. Treatment with the laser has certain advantages like the selective removal of affected epithelium and minimal damage to surrounding healthy tissue, resulting in excellent wound healing with no or minimal scar tissue and a good functional result. Almost all treatments can be done under local anesthesia on an outpatient basis. The most important disadvantage of CO2 laser evaporation of oral leukoplakia is the fact that the lesion is not available for histology and this investigation is only done on small incisional biopsies. The location of the lesion must therefore be carefully chosen. If the lesion is large or shows different clinical aspects, more than one biopsy is recommended. Also a good knowledge of the etiologic factors, biologic behavior of the lesion, and a histologic diagnosis is necessary and important. This large study with a long follow up shows that CO2 laser treatment in experienced hands and with good follow up is a good prophylactic treatment for oral leukoplakia.
References 1. Axe ´ll T, Pindborg JJ, van der Waal I. Oral white lesions with special reference to precancereus and tobacco-related lesions: conclusions of an international symposium held in Uppsala, Sweden, May 18–21, 1994. J Oral Pathol Med 1996;25:49–54. 2. Roodenburg JLN, Panders AK, Vermey A. Carbon dioxide laser surgery of oral leukoplakia. Oral Surg Oral Med Oral Pathol 1991;71:670–4. 3. Gooris PJJ, Roodenburg JLN, Vermey A, Nauta JM. Carbon dioxide laser evaporation of leukoplakia of the lower lip: a retrospective evaluation. Oral Oncol 1999;35:490–5. 4. Silverman S, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. Cancer 1984;53:563–8. 5. Pindborg JJ, Jolst O, Renstrup G, Roed-Petersen B. Studies in oral leukoplakia: a preliminary report on the period prevalance of malignant transformation in leukoplakia based on a follow up study of 248 patients. J Am Dental Assoc 1968;76:767–71. 6. Vedtofte P, Holmstrup P, Hjorting-Hansen E, Pindborg JJ. Surgical treatment of premalignant lesions of the oral mucosa. Int J Oral Maxillofac Surg 1987;16:656–64. 7. Chiesa F, Boracchi P, Tradati N, Rossi N, Costa L, Giardini R, et al. Risk of preneoplastic and neoplastic events in operated oral leukoplakias. Oral Oncol, Eur J Cancer 1993;29: 23–8. 8. Jones GM, Shepherd JP, Scully C. A case of squamous cell carcinoma arising in an area treated with a carbon dioxide laser. Br J Oral Maxillofac Sur 1987;25:57–60. 9. Hogewind WFC, van der Kwast WAM, van der Waal I. Oral leukoplakia, with emphasis on malignant transformation. J Cranio Maxillofac Surg 1989;17:128–33.
Results of CO2 laser surgery in patients with oral leukoplakia 10. Saito T, Sugiura C, Hirai A, Notani K, Totsuka Y, Shindoh M, et al. Development of squamous cell carcinoma from preexistent oral leukoplakia: with respect to treatment modality. Int J Oral Maxillofac Surg 2001;30:49–53. 11. Ishii J, Fujita T, Komori T. Laser surgery as a treatment for oral leukoplakia. Oral Oncol 2003;39:759–69. 12. Schepman KP, van der Meij EH, Smeele LE, van der Waal I. Malignant transformation of oral leukoplakia: a follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands. Oral Oncol 1998;34:270–5. 13. Van der Waal I, Schepman KP, van der Meij, Smeele LE. Oral Leukoplakia: a clinicopathological review. Oral Oncol 1997;33:291–301. 14. Bekke JP, Baart JA. Six years experience with cryosurgery in the oral cavity. Int J Oral Surg 1979;8:251–70. 15. Gongloff RK, Samit AM, Greene Jr GW, Inneo GF, Gage AA, Buffalo NY. Cryosurgical management of benign and dysplastic intraoral lesions. J Oral Surg 1980;38:671–6. 16. Sako K, Marchetta FC, Hayes RL. Cryotherapy of intraoral leukoplakia. Am J Surg 1972;124:482–4. 17. Ishida CE, Ramos-e-Silva M. Cryosurgery in oral lesions. Int J Dermatol 1998;37:283–5. 18. Chu FWK, Silverman Jr S, Dedo HH. CO2 laser treatment of oral leukoplakia. Laryngoscope 1988;98:125–30. 19. Flynn MB, White M, Tabah RJ. Use of carbon dioxide laser for the treatment of premalignant lesions of the oral mucosa. J Surg Oncol 1988;37:232–4. 20. Frame JW. Removal of oral soft tissue pathology with the CO2 laser. J Oral Maxillofac Surg 1985;43:850–5.
37
21. Kardos TB, Holt T, Ferguson MM. Histological evaluation of the effect of a miniature carbon dioxide laser on oral mucosa. Int J Oral Maxillofac Surg 1989;18:117–20. 22. Thomson PJ, Wylie J. Interventional laser surgery: an effective surgical and diagnostic tool in oral precancer management. Int J Oral Maxillofac Surg 2002;31: 145–53. 23. White JM, Chaudry SI, Kudler JJ, Sekandari N, Schoelch ML, Silverman Jr S. Nd: YAG and CO2 laser therapy of oral mucosal lesions. J Clinical Laser Med and Surg 1998;16:299–304. 24. Schoelch ML, Sekandari N, Regezy JA, Silverman Jr S. Laser management of oral leukoplakias: a follow-up study of 70 patients. The Laryngoscope 1999;109:949–53. 25. Horch HH, Gerlach KL, Schaefer HE. CO2 laser surgery of oral premalignant lesions. Int J Oral Maxillofac Surg 1986;15:19–24. 26. Chiesa F, Tradati N, Sala L, Costa L, Podrecca S, Boracchi P, et al. Follow-up of oral leukoplakia after carbon dioxide laser surgery. Archives of Otolaryngology and Head and Neck Surg 1990;116:177–80. 27. Roodenburg JLN, Panders AK, Vermey A, Verschueren RCJ. Treatment of superficial lesions of the oral mucosa with the carbon dioxide laser. J Exp Clin Cancer Res 1983;3: 283–6. 28. Fisher SE, Frame JW. The effects of the carbon dioxide surgical laser on oral tissues. Br J Oral Maxillofac Surg 1984;22:414–25. 29. Silverman S, Chu FWK, Dedo HH. CO2 laser treatment of oral leukoplakia. Laryngoscope 1988;98:125–30.
http://intl.elsevierhealth.com/journals/oron/
The results of CO2 laser surgery in patients with oral leukoplakia: a 25 year follow up P.S. van der Hem*, J.M. Nauta, J.E. van der Wal, J.L.N. Roodenburg Department of Oral and Maxillofacial Surgery, Groningen University Hospital, P.O. Box 30001, 9700 RB Groningen, The Netherlands Received 29 April 2004; accepted 3 June 2004
KEYWORDS
Summary Oral leukoplakia is an important premalignant lesion of the oral mucosa. We treat this lesion prophylactically with CO2 laser evaporation. In the period from 1976 to 2001, a group of 200 patients with 282 oral leukoplakias were treated by CO2 laser evaporation. In a follow up period of 1–219 months (mean 52), 251 treated leukoplakias (89.0%) did not show a recurrence. Twenty eight (9.9%) local recurrences were observed in 5 to 168 months after treatment. Three (1.1%) squamous cell carcinoma, occurred in the treated area respectively 7, 17 and 19 month after CO2 laser evaporation. This large study with a long follow up shows that laser treatment is a good prophylactic treatment for oral leukoplakia. c 2004 Elsevier Ltd. All rights reserved.
Oral leukoplakia; Carbon dioxide laser surgery; Recurrence; Epithelial dysplasia; Malignant transformation
Introduction Oral leukoplakia is a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion; some oral leukoplakias will transform into cancer.1 Histologically, leukoplakia is an intraepithelial lesion consisting of epithelial hyperplasia, with or without hyperkeratosis and minimal inflammation, and with or without varying degrees of dysplasia. As stated, oral leukoplakia can transform into a malignant lesion. According to the literature the * Corresponding author. Tel.: +31 50 361 2567; fax: +31 50 361 1136. E-mail address: [email protected] (P.S. van der Hem).
overall chance of malignant transformation varies from 0.13% to 17.5%.2 This is related to the clinical and histological classification and the location of the lesion. Lesions that are at high risk are clinical nonhomogeneous (verrucous and erosive) types, lesions with histologically epithelial dysplasia and the lesions that are located on the borders of the tongue and floor of mouth.2,3 Factors associated with an increased risk of malignant transformation are the gender (female); duration (years); idiopathy of the lesions, and presence of Candida albicans.4–13 Conventional types of treatment have been excision by scalpel, and cryosurgery. The recurrence rate varies for excision from 10% to 34%4–6 and for cryosurgery from 12% to 25%14–17 according to literature. These modalities cause scarring, contraction and can mask early signs of recurrence.2,18
1368-8375/$ - see front matter c 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.oraloncology.2004.06.010
32
P.S. van der Hem et al. Table 1 Age and sex distribution of 200 patients with an oral leukoplakia n
Age (yr)
Mean (yr)
Men Women
109 91
30–79 33–86
56.5 67.5
Total
200
30–86
59.5
Table 2 patients
Localization of 282 oral leukoplakias in 200
Location
Figure 1 scanner.
The Sharplan 40C CO2 laser with a Surgitouch
Since 1970s, studies have shown that the CO2 laser (Fig. 1) is an effective instrument for the treatment of premalignant lesions of the oral mucosa. Soft tissues can be superficially removed by evaporation with minimal thermal damage to adjacent tissue, which results in minimal tendency to scar and little postoperative pain and edema.19–21 Using a CO2 laser, selective removal of epithelium can be performed. Therefore this modality is very suitable for the treatment of intraepithelial lesions like oral leukoplakia.22,25–28 The aim of this study was to look at the recurrence rate and degeneration into malignancy in a large group of patients with oral leukoplakia, after treatment with CO2 laser surgery with a long period of follow up. In this study we use cases who were already used in the evaluation of 1991.2
n
Upper lip Lower lip Labial commissure Buccal mucosa Floor of mouth Tongue Palate Gingiva Anterior tonsillar pillar
4 21 21 58 55 64 10 36 13
Total
Table 3
282
% 1.4 7.5 7.5 20.6 19.5 22.7 3.6 12.6 4.6 100
Size of 282 oral leukoplakias in 200 patients
Size (cm) \2 2.4 [4 Total UnKnown
n
%
45 78 10
33.8 58.7 7.5
133 149
100
the lesions was classified as less than 2 cm, 2–4 cm, and more than 4 cm (Table 3). The tongue, buccal mucosa and floor of mouth were the areas most frequently affected (Table 2). According to the clinical classification, 136 (69%) homogeneous
Material and methods Leukoplakia In the period from 1976 to 2001, 200 patients with 282 oral leukoplakias were treated by CO2 laser evaporation. This group was followed until 2001. The sex and age distribution is given in Table 1. Of these 200 patients, 62 (31%) had been treated previously for a squamous cell carcinoma of the oral mucosa. In 68 patients, there was multifocal leukoplakia. The frequency of the lesions in the several locations is shown in Table 2. The size of
Table 4 Histology of the primary lesion in 200 patients with an oral leukoplakia Dysplasia
n
No Little Moderate Severe Squamous cell carcinoma
152 47 28 12 3
Total
242
% 62.8 19.4 11.6 5.0 1.2 100
Results of CO2 laser surgery in patients with oral leukoplakia and 61 (31%) nonhomogeneous leukoplakias were treated. The group of nonhomogeneous lesions was divided into 31 (16%) verrucous and 30 (15%) erosive leukoplakias. The histology of the lesions is shown in Table 4.
Laser equipment In the period from 1976 to 2001, oral leukoplakia was treated by evaporation with a CO2 laser. The first 17 treatments were performed with the handpiece, later, a micromanipulator together with an operation microscope (Zeiss Opmi 1) (Fig. 2) was used. During this period several CO2 laser systems were used with the same physical characteristics. These systems were respectively the Sharplan 791, the Cavitron and the Sharplan 40C. Because the CO2 laser produces a straight light beam, not every location in the mouth can be reached. Therefore we developed an endoscope (Fig. 3) with a 45°
33
stainless steel mirror that was coupled to the micromanipulator. With this equipment all sides of the oral cavity could be treated.
Patient management Patients with an oral leukoplakia (Fig. 4a) received a complete physical head and neck examination. The lesion was classified according to possible cause, location, clinical appearance, and gender and age of the patient. For histologic classification one or more incisional biopsies were taken under local anesthesia. If possible, etiologic factors were eliminated. Almost all treatments (96%) were carried out with the patient under local anesthesia on an outpatient basis. General anesthesia was necessary only for treating locations
Figure 2 The micromanipulator together with the operation microscope (Zeiss Opmi 1).
Figure 3 The endoscope with a 45° stainless steel mirror coupled to the micromanipulator.
Figure 4 (a) A patient with erosive leukoplakia with severe dysplasia in the floor of mouth and the ventral side of the tongue. (b) The situation directly after CO2 laser evaporation. (c) Wound healing four weeks after CO2 laser evaporation.
34 that were otherwise not accessible, such as the soft palate. In the case of general anesthesia the endotracheal tube was covered with a reflective metal tape to prevent accidental perforation by the laser beam. Nowadays endotracheal laser tubes are available. The use of explosive gasses should be avoided. We preferred an operation microscope and micromanipulator to perform the treatment. This gives the advantage of optical magnification and a stable system to aim the laser beam at the area to treat, resulting in an excellent control over the procedure. The treatment was carried out by moving a slightly defocused CO2 laser spot of about 1 mm over the lesion until it was completely evaporated and the submucosa was reached (Fig. 4b). A margin of about 3 mm around each lesion was taken. Output powers of 15–20 W were used, and defocusing of the beam was achieved by elevating the focus of the handpieces a few millimeters above the tissue surface, or by a adjustable lens in the micromanipulator. The Sharplan 40C was used with a scanning device (Surgitouch) connected with the operation microscope. With the scanning device it was possible to use the laser beam in focus and to reduce carbonization. Small lesions were treated in one session; larger lesions took two or more treatments. For postoperative care a 0.1% chlorhexidine mouthwash and paracetamol analgesic were prescribed. In case of lesions of the vermillion border of the lip vaseline was used for wound care. After treatment, the patients were seen for follow up after 4 weeks, 3 months, and 6 months, and were subsequently followed up on a yearly basis during the whole period. A local recurrence was defined as a leukoplakia arising within the borders of the treated area.
Results Wound healing took place by epithelization from the border of the wound. In almost all cases this healing was complete within 4 weeks (Fig. 4c). After healing, there was almost no clinically perceptible difference in appearance or elastic properties of the laser-treated mucosa to normal mucosa. In a mean follow up period of 52 months range (1–219 months), 251 treated leukoplakias (89.0%) did not show a recurrence. The follow up of 15 lesions was ended because of interrecurrent death, in 49 cases because the patient moved and was lost to follow up or the follow up was carried out by the dentist or in another hospital. These cases were excluded from the study. In 13% of the recurrence-free cases a biopsy was taken, which confirmed the clinical result. In the
P.S. van der Hem et al. group of 282 treated leukoplakias, 28 (9.9%) local recurrences were observed. These recurrences occurred in a mean period of 87 months (5–168) after treatment and were confirmed by biopsy. In four of the 28 cases, the recurrences showed higher degree of dysplasia than in the earlier treated lesion. There were 3 (1.1%) cases in which a squamous cell carcinoma occurred, respectively 7, 17 and 19 month after treatment. There was no relationship to the clinical or histologic classification of the treated lesion and the appearance of a recurrence. Table 4 shows the histology of all the primary lesions which were biopsied. All 28 recurrences in the leukoplakia group, were retreated by CO2 laser evaporation and 27 of these recurrences were recurrence free after one to four retreatments. One patient was not recurrence free even after another three retreatments. Of the recurrences 18 occurred in male patients and 10 in female patients. Of the 28 recurrences, there were 12 smokers. Thirteen of these leukoplakias were localized on tongue cq floor of mouth. Of the recurrences that were biopsied two showed histologically moderate and one severe dysplasia. Twenty-three of the recurrences were homogenous, two were verrucous and three erosive. Twelve (43%) recurrences developed within three months, five (18%) within six month, nine (32%) within one year and two (7%) after one year. From the 28 recurrences, there were eight multifocal leukoplakias (29%). There were 14 (50%) patients with an oral tumor in the past. From the cases which showed malignant transformation, initial biopsies showed in one case severe dysplasia and no dysplasia in two cases. Two were localized at the floor of mouth and one at the tongue. There were two males and one woman. Two of them were smokers, one man and one woman. Clinically there were two homogeneous and one erosive lesion.
Discussion In comparing our present results with the evaluation of 1991 we see a comparable recurrence rate. In 1991, 70 patients with 103 lesions were treated, with a mean follow up of 5.3 years (0.5–12). There were 10 recurrences which is 10% (Table 5), 7–55 month after treatment. No transformation into squamous cell carcinoma was seen. From the 10 recurrences, 4 were treated again and did not show recurrence. In our present study we have treated 200 patients with 282 lesions with a mean follow
Results of CO2 laser treatment in oral leukoplakia in the literature
Treatment
Author (yr)
n
Cured
n Surgery Cryosurgery
CO2 laser evaporation or excision
Recurrence
Squamous carcinoma cell
%
n
%
n
Vedtofte (1987) Silverman (1984)
61 61
40
66
20 21
34
5 0
Sako (1972) Bekke (1979) Gongloff (1980)
69 24 15
48 18 13
80 75 87
8 3 8
13 12 13
4 0 0
93
90
10 10 4 6 21
10.8 10
0
Silverman (1988) Roodenburg (1991) Gerlach (1993) White (1998) CO2 YAG Schoelch (1999) YAG Thomson (2002) Ishii (2003) Present study
38 103 233 17 22 55 57 82 282
45 58 254
89.0
12 24 28
Mean
% 1.0–5.0 yr 7.2 yr 7
2.6
23.5 27.2 38.1 24 29.3 9.9
Follow up
2.5–4.5 yr 0.1–5.2 yr 0.7–4.4 yr 3–10 yr 6–144 month 0–3.8 yr
2.5 yr 2.2 yr 5 yr
Results of CO2 laser surgery in patients with oral leukoplakia
Table 5
6–178 month 4 1 3
7 1.2 1.1
1–44 month
18 month
1–219 month
35
36 up of 4.3 years (1–219 months). There were 28 recurrences which is 9.9%, 5–168 month after treatment. Twenty-seven lesions were recurrence-free after 1–4 retreatments. However three cases (1.1%) showed malignant transformation after 7, 17 and 19 month. The initial biopsies showed severe dysplasia (1 case) and no dysplasia (2 cases). Early malignant transformation can be explained by a sampling error of the incisional biopsy. When small biopsy specimens are taken, there is a chance of missing an area of malignancy. Therefore, the biopsy specimens must be taken from the most suspicious area such as erosions or verrucous changes. Large lesions require more than one biopsy. Two of the squamous cell carcinomas were localized in the floor of mouth and one at the border of the tongue. There were two women and one man. Two were smokers, one man and one woman. Two of the leukoplakias were homogenous and one erosive. Histologically there was initially one severe dysplasia and two showed no dysplasia. Except for etiologic factors, there was no correlation between the several classifications of the leukoplakia and the development of a recurrence or squamous cell carcinoma. Due to excellent wound healing after CO2 laser evaporation, a squamous cell carcinoma can easily be recognized by clinical evaluation. Therefore, careful follow up is mandatory after treatment. The cure rate of 89.0% in our study of CO2 lasertreated leukoplakias is remarkably high as compared to other studies (Table 5).2,4,6,11,14–16,22–24,29 When one looks at the results of excision this can be explained by a remaining etiologic factor, however in our study 16 recurrences (57%) were nonsmokers. Etiologic factors might play a role in the difference in cure rate in case of cryosurgery. An important difference between cryosurgery and laser treatment is that with CO2 laser the effect can be directly observed. With cryosurgery the tissue is rejected afterwards as necrosis, so the depth of the treatment is not as well controlled as compared with the CO2 laser evaporation in combination with an operation microscope. Comparing our present results with the evaluation of 1991 there is a small increase in the cure rate in a much longer follow up period. So within a long period of time we did not see a significant increase in the amount of recurrences. The lower cure rate of former studies by others may be caused by the technique. Some studies performed the treatments with a handpiece, whereas we used the micromanipulator and operation microscope in 81% of the treatments. By using the operation microscope, there is a better control of the treatment.
P.S. van der Hem et al.
Conclusions With excision, cryosurgery and CO2 laser evaporation for the treatment of oral leukoplakia, good cure rates can be obtained. Treatment with the laser has certain advantages like the selective removal of affected epithelium and minimal damage to surrounding healthy tissue, resulting in excellent wound healing with no or minimal scar tissue and a good functional result. Almost all treatments can be done under local anesthesia on an outpatient basis. The most important disadvantage of CO2 laser evaporation of oral leukoplakia is the fact that the lesion is not available for histology and this investigation is only done on small incisional biopsies. The location of the lesion must therefore be carefully chosen. If the lesion is large or shows different clinical aspects, more than one biopsy is recommended. Also a good knowledge of the etiologic factors, biologic behavior of the lesion, and a histologic diagnosis is necessary and important. This large study with a long follow up shows that CO2 laser treatment in experienced hands and with good follow up is a good prophylactic treatment for oral leukoplakia.
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