Carbon dioxide laser surgery of oral leukoplakia J. L. N. Roodenburg, DDS, PhD,a A. K. Panders, DDS, PhD.” and A. Vermey, MD, PhD, FACS,b Groningen, The Netherlands UNIVERSITY

HOSPITAL

GRONINGEN

Oral leukoplakia is a precancerous lesion of the oral mucosa. The risk of malignant transformation depends on the clinical and histologic classification and the location of the lesion. For a nonhomogeneous leukoplakia, this risk is 23.4% to 38.0%. In the presence of epithelial dysplasia, the possibility of malignant transformation is 36.3% to 43.00/o. Leukoplakia is limited to the epithelium, so a selective removal of this part of the mucosa seems to be the best preventive treatment. Carbon dioxide laser surgery accomplishes a superficial removal by evaporation. A total of 70 patients with 103 oral leukoplakias were treated with carbon dioxide laser evaporation. This resulted in an excellent wound healing with virtually no scarring. The patients were followed up during a period of up to 12 years (mean 5.3 years), showing a cure rate of 90%. (ORAL SURC ORAL MED ORAL PATHOL 1991;71:670-4)

A

ccording to the definition of the World Health Organization, oral leukoplakia is a white patch of the oral mucosa that cannot be scraped off and that cannot be characterized clinically or pathologically as any other disease.” * Oral leukoplakia is a clinical diagnosis.3 Histologically, it is an intraepithelial lesion consisting of epithelial hyperplasia, orthokeratosis, or parakeratosis with or without dysplasia. Oral leukoplakia is a precancerous lesion.4 According to the literature, 5, 6 the overall chance of malignant transformation varies from 0.13% to 17.5%. A more detailed clinical classification of oral leukoplakia can be helpful to find lesions that are at high risk such as the nonhomogeneous (verrucous and erosive) types, 23.4% to 38.O%.6-8 The presence of epithelial dysplasia gives an increase of the risk of 36.3% to 43.0%.6 With respect to the site, leukoplakias of the lateral border of the tongue (27.3%’ to 44.4%l”) and floor of the mouth (24.1%” to 50.0%8) are especially at risk. The surgical treatment modalities until now have been excision by scalpel, cryosurgery, and electrocoagulation. The recurrence rate for local excision varies from 10% to 34%.6, ‘* For cryosurgery the recurrence rate is 13% to 25%.13* I4

None of these treatments has the possibility of removing just the affected epithelium. Because of the strong absorption in soft tissues, carbon dioxide laser light causes a superficial evaporation with minimal thermal damage to the surrounding tissues. *5-17With this method a selective removal of epithelium can be performed (Fig. 1). Therefore CO2 laser evaporation seems to be a useful tool in the treatment of oral leukoplakia.

aDepartment Oncology. bDepartment 7/12/18741

bukoplakia

670

of

Oral

and

of Surgery/Oncology.

Maxillofacial

Surgery,

Division

of

MATERIAL Laser

AND METHODS

equipment

In the period from 1976 to 1983, oral leukoplakia was treated by evaporation with a Sharplan 791 CO2 laser. The first 17 treatments were performed with the handpieces; later, a micromanipulator (American Optical Corp.) together with an operation microscope (Zeiss Opmi I) was available. Since 1983 we have used a Cavitron 300A CO2 laser and micromanipulator (Cooper Medical Corp., Stamford, Conn.). Because the CO2 laser produces a straight light beam, not every location in the mouth can be reached. Therefore we developed an endoscope with a 45degree stainless steel mirror that was coupled to the micromanipulator (Fig. 2). With this equipment the lingual side of the mandible and the retromolar area could be treated.

In the period from 1976 to 1984, a group of 70 patients with 103 oral leukoplakias were treated by CO2

Volume Number

7I 6

CO2 laser surgery of oral leukoplakia

671

Fig. 1. Effect of CO2 laser light on mucosa of dorsal side of tongue of Wistar albino rat. k, Crater resulting from evaporation. c, Carbonization. d, Thickness of zone of irreversible thermal damage to tissues. Fig. 2. Endoscope with 45-degree stainless steel mirror, connected to micromanipulator.

laser evaporation. This group was followed up until 1988. The sex and age distribution is given in Table I. Of these 70 patients, 24 (34%) had been treated previously for a squamous cell carcinoma of the oral mucosa. In 25 patients there was multifocal leukoplakia. The frequency of the lesion in the several locations is shown in Table II. The size of the lesions was classified as smaller than 2 cm, 2 to 4 cm, and larger than 4 cm (Table III). According to the clinical classification, 62 homogeneous and 41 nonhomogeneous leukoplakias were treated. The group of nonhomogeneous lesions was divided into 18 verrucous and 23 erosive leukoplakias. The amount of dysplasia is shown in Table IV.‘, I8 Patient management

Patients with an oral leukoplakia received a complete physical head and neck examination. The lesion was classified according to possible cause, location, clinical appearance, and the sex and age of the patient. For histologic classification one or more incisional biopsy specimens were taken with the patient under local anesthesia (Fig. 3). If possible, etiologic factors such as tobacco use or Candida infection were corrected before treatment. The treatment was carried out by moving a slightly defocused CO2 laser spot over the lesion until it was completely evaporated and the submucosa was reached (Fig. 4). A margin of about 3 mm around each lesion was taken. Output powers of 15 to 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. If the operation microscope was used, defocusing was achieved by using a laser lens with a focal length of 400 mm and a 300 mm lens in the microscope.

Table I. Sex and age distribution with oral leukoplakia

Men Women Total

n

Age (~4

38 32 70

30-78 26-88 26-88

of 70 patients Mean

(yr)

59.9 60.5 58.6

Almost all treatments (90%) were carried out with the patient under local anesthesia on an outpatient basis. General anesthesia was necessary only for treating locations that were otherwise hardly 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. The use of explosive gases should be avoided. Small lesions were treated in one session; larger lesions took two or more treatments. For postoperative care a 0.1% chlorhexidine mouthwash and 500 mg paracetamol analgesic were prescribed. In cases of lesions of the vermilion border of the lip petroleum jelly was used for wound care. After treatment, the patients were seen back in 4 weeks, 3 months, and 6 months, and they 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 epithelialization from the border of the wound (Fig. 5). In almost all cases

Roodenburg,

672

Panders, and Vermey

Table

Ill. Distribution

Size icnr)

Table

Fig. 3. Homogeneous sia of lower lip.

Table

II. Distribution

leukoplakia

of lesions among various sites n

Upper

lip

Lower

lip + vermilion

I

Labial commissure Buccal mucosa of mouth

Tongue

border

II 17 29 10 IS 3

Palate Gingiva Anterior

T

tonsillar

pillar

I3 I

I II I6 28 IO 17 3

13 I

9;

4

63 9

hi 9

IV. Distribution

to dysplasia

Dysplasia

n

%,

None

70

Slight Moderate

I5 I3

68 I4

Severe

Location

Floor

with moderate dyspla-

of size of lesions 7.---li

5

13 5

confirmed by biopsy. A degeneration into a squamous cell carcinoma was not seen. Five of the cases of recurrence involved patients who continued smoking; the other five recurred in patients in whom the etiologic factors were unknown. There was no relationship to the clinical or histologic classification of the treated lesion and the appearance of a recurrence. Of the 10 recurrences in the leukoplakia group, four were retreated by CO2 laser evaporation and did not show a recurrence. DISCUSSION

(95%) this healing was complete in 4 weeks. After healing there was almost no clinically perceptible difference in appearance or elastic properties of the laser-treated mucosa to normal mucosa. The use of analgesics was evaluated after 50 treatments. In 41% of the cases none was used; in 46% the analgesics were used for fewer than 6 days. Only in 13% of the cases was paracetamol used longer than 6 days or were more powerful analgesics necessary. There was no correlation to the size or site of the treated leukoplakia and the pain. In a follow-up period of 0.5 to 12 years (mean 5.3 years), 93 of the 103 treated leukoplakias (90%) did not show a recurrence. The follow-up of 14 lesions was ended because of intercurrent death, and in 15 cases because the patient moved and was lost to follow-up. Of these last 15 cases, there was a follow-up of at least 2 years and in 7 cases even more than 5 years. In 39% of the recurrence-free cases a biopsy was taken, which confirmed the clinical result. In the group of 103 treated leukoplakias, 10 (10%) local recurrences were observed. These recurrences occurred 7 to 55 months after treatment and were

The technique of CO2 laser evaporation of oral leukoplakia is more easily performed than excision with the knife. This is especially of interest if large lesions or leukoplakias around ducts of salivary glands or close to the teeth are treated. General anesthesia is rarely indicated. The most remarkable observation after healing of a CO* laser-treated leukoplakia was the limited formation of scar tissue. From observations in animal experiments we believe this type of wound healing is a result of the selective removal of epithelium and the minimal thermal damage to the surrounding tissue. 19,2oThis results in a good functional situation for the patient and a good possibility for inspection. The cure rate of 90% in our study of CO2 lasertreated leukoplakias is remarkably high as compared with other studies (Table V). When one looks at the results of excision, this can be partly explained by the longer follow-up period of these studies.6T‘, I03‘l. 2’ Another reason can be a remaining etiologic factor, especially tobacco use. The difference in cure rate in the cryosurgery studies cannot be explained by the duration of the follow-up period. Etiologic factors may play a role. An important difference between cryosurgery and laser treatment is that

Volume Number

CO2 laser surgery of oral leukoplakia

7I 6

Fig. 4. Wound directly

673

Fig. 5. Wound healing 6 weeks after CO2 laser evapora-

after CO2 laser evaporation.

tion.

Table V. Results of several treatment

modalities of oral leukoplakia

Cured Treatment

Author

Surgery

CO2

n

(I 968)‘* ( 1972)*l

21 18

19 I

90 6

(Surg) Bzin6czy Bin&y

(1976)‘O (1977)’

74 45 ?

59 36

80 80 0

9 61

40

70 66

Hausamen (I 973)26 Bekke (I 979)13 Gongloff (1 980)14

15 24 15

I5 18 13

100 75 87

Sako

69

48

80

75 15

69 II

92 73

32 51

32 48

78 94

103

94

91

103 38

93 37

90 97

(I 984)6

(1972)*’

4

Unchanged 5%

n

%

22

7

39

14

19

7

I6 30 28

3

Increased n

I 36

Recurrence 96

n

%

2 6

IO 33

0 0

I

1

0 I 0

2 33 2

13

n

%

2

0 21

34

0

3 2

12 13

0 0 0

8

13

4

Follow-up

Mean

1-8 yr

3.8 yr

I-20 I-20

yr yr

8.6 yr 6.3 yr

l-30

yr 7.2 yr

7

0.1-5.2 0.7-4.4

yr yr

2.5-4.5

yr

1.5 yr 2.2 yr 2.5 yr

laser

evaporation

Frame Horch

( 1985)28 (I 982)‘*

Horch (1983)** Roodenburg ( 1983)29 Roodenburg

( 1985)19

Roodenburg (I 990) Chu ( 1988)23 S~rg, Surgery *B!

nn%

Pindborg BBn6czy

(SW4 Silverman Cryosurgery

(y)

Improved

Squamous cell carcinoma

after clinliniltion

reexamination

this

lc\iOn

of etiologic wa\ already

6

8

4 7

27

0

22

0

2 9 10

4 90

3-9 mo 1 mo 3-69 6-95

mo mo

36 mo

mo

38 mo

0.5-12 3-9.5

yr yr

5.3 yr 5.2 yr

9-15

1*

2

IO I

3

29 mo

faclors. in the beginning

a squamous

cell carcinoma.

with the CO2 laser the tissue is removed during the treatment and the effect can be directly observed. With cryosurgery the tissue is rejected afterward as necrosis, so the depth of the treatment is not as easily controlled as compared with the CO2 laser evaporation. In comparing our present results with the evaluations of 1983 and 1985, there is a small decrease in the cure rate because of the longer follow-up period. The lower cure rate of the studies of Horch’$ and

Horch et a1.22may be caused by the technique. Horch performed the treatments with a handpiece, whereas we used the micromanipulator and operation microscope in 84% of the treatments. By using the operation microscope, there is a better control of the treatment. As for technique and follow-up, the study of Chu et a1.23 is comparable to ours. The higher cure rate is partly due to the fact that the results of the treatment of four recurrences (8%) are included as well. In con-

674

Roodenburg, Panders, and Vermey

trast to our study, Chu et a1.23observed one squamous cell carcinoma after CO2 laser evaporation of an oral leukoplakia. In the literature24 one other squamous cell carcinoma after CO2 laser treatment of an oral leukoplakia is reported. We are of the opinion that these squamous cell carcinomas were not induced by the CO2 laser light. In an experimental study by Apfelberg et a1.,25no malignant transformation could be induced by CO2 laser light. An explanation for this “malignant transformation” could be a sampling error of the incisional biopsy. When small biopsy specimens are taken, there is a chance of missing an area of malignant degeneration. Therefore the biopsy specimens must be taken from the most suspect area such as erosions or verrucous changes. Large lesions require more than one biopsy. CONCLUSIONS

For treatment of oral leukoplakia a good knowledge of the etiologic factors and biologic behavior of the lesion and a histologic diagnosis are necessary. With excision, cryosurgery, and CO2 laser evaporation, good cure rates can be obtained. The most important advantages of the use of the CO:! laser are l the possibility of combining the laser with an operation microscope, which yields a more precise control l the selective removal of affected epithelium and minimal damage to surrounding healthy tissues l the excellent wound healing, with virtually no scarring and a good functional result l the possibility of doing almost all treatment with the patient under local anesthesia on an outpatient basis The most important disadvantage of CO2 laser evaporation of oral leukoplakia is that the histology is done on small incisional biopsy specimens. Therefore a careful follow-up is needed. REFERENCES 1. Kramer IRH, Lucas RB, Pindborg JJ, Sobin LH. Definition of leukoplakia and related lesions: an aid to studies on oral precancer. ORAL SURG ORAL MED ORAL PATHOL 1978;46: 518-39. 2. Axe11 T, Gupta PC, Hansen L. et al. Diagnostic and therapcutic problems of oral precancerous lesions. Int J Oral Maxillofat Surg 1986;15;790-8. 3. Axill T, Holmstrup P, Kramer IRH, Pindborg JJ, Shear M. International seminar on oral leukoplakia and associated lesions related to tobacco habits. Community Dent Oral Epidemiol 1984;12:145-54. 4. Pindborg JJ. Oral cancer and precancer. Bristol: Wright, 1980: 15. 5. Silverman S, Bhargarva K, Mani NJ, Smith LW, Malaowalla AM. Malignant transformation and natural history of oral leukoplakia in 57,518 industrial workers of Gujarat, India. Cancer 1976:38:1790-5. 6. Silverman S, Gorsky M, Lozada F. Oral leukoplakia and malignant transformation. Cancer 1984;53:563-8.

ORAI.

SIR