Treatment Outcome of Oral Leukoplakia with Er:YAG Laser: A 5-Year Follow-Up Prospective Comparative Study

Abstract

Objective:

The purpose of this prospective analysis was to evaluate the efficacy of erbium-substituted yttrium aluminum garnet (Er:YAG) laser compared with that of conventional surgery, regarding the long-term outcome of nondysplastic oral leukoplakias (OL).

Background:

To date, this comparison has never been performed.

Methods:

Patients were randomly allocated to two different groups: some underwent surgical excision with traditional scalpel (Group TrSc) and others underwent an ablative session with Er:YAG laser (Group Las), with these modalities: 1.5-W power, 150-mJ pulse energy, 10-Hz frequency, 500-μs pulse duration, and 0.9-mm spot size. During the follow-up period, the evolution of the OL was listed as (1) healing: if novel lesions did not appear in the same place of the surgery and (2) recurrence: if a new mucosal change has been detailed in the equivalent place of the primary disease.

Results:

One hundred seventeen lesions were treated. Fifty-eight lesions underwent surgery with traditional scalpel, whereas 59 underwent laser surgery. Follow-up ranged from 24 to 108 months (median of 58). Healing was detailed for 52.99% (n = 62) of the 117 OL, with no statistical differences between the two randomized groups.

Conclusions:

It seems reasonable to consider the Er:YAG laser as effective as traditional scalpel in terms of healing for OL, with the same rate of recurrences in a period of almost 5 years.

Introduction

It has been stated that a temporary diagnosis of oral leukoplakia (OL) should be completed when a white lesion, during a clinical examination, cannot be plainly diagnosed as any other disease or disorder of the oral cavity.¹

Cold knife is the paramount treatment option as far reported, being sometimes more challenging mainly due to difficulties in suturing.²

Various lasers have been recently introduced in oral surgery, CO₂ laser being the more frequently described;³ however, among them, erbium-doped yttrium aluminum garnet (Er:YAG) laser could deliver acceptable cutting and coagulation effects.^4,5

Very recently, we have published a surgical trial reporting the management of nondysplastic oral lesions with an Er:YAG laser in comparison with traditional scalpel surgery and reported statistical differences in the immediate postoperative surgical period between the two treatments, showing the laser surgery to be less painful and better accepted.⁶

The aim of this new prospective study was to estimate the effectiveness of an Er:YAG laser compared with that of a traditional scalpel surgery in the long-term outcome for nondysplastic OL.

Patients and Methods

Consecutive subjects, attending the Oral Medicine Unit of the CIR Dental School, from September 2008 to June 2010, after referral for histological evaluation of oral homogeneous white patches, were clinically assessed by a qualified oral healthcare provider (P.G.A.). Having excluded other causes of white patches, as reported in the literature,^1,2 clinical diagnosis was primarily based on visual inspection and manual palpation. Moreover, an incisional biopsy was undertaken to obtain the histological diagnosis of hyperkeratosis without signs of dysplasia. After this, the inclusion and exclusion criteria were assessed as previously reported.⁶

Eight weeks after histological diagnosis, patients underwent a second complete surgical session. The same experienced oral surgeon (R.B.) performed both.⁶ Patients were randomly allocated to two different groups: some underwent the surgical excision with traditional scalpel (Group TrSc) and the others underwent an ablative session with Er:YAG laser (Group Las). A Fidelis plus3™ Er:YAG laser (λ = 2940 nm), with an R0₂-C hand-piece, was used (Fotona™, Ljubliana, Slovenja), according to manufacturer's instructions: 1.5-W power, 150-mJ pulse energy, 10-Hz frequency, 500-μs pulse duration, and 0.9-mm spot size.⁶

During the follow-up period, the development of the OL was described as follows:⁷

Healing: if new lesions did not appear in the same place of the primary biopsy.

Recurrence: if a new mucosal change has been detailed again in the same place of the primary disease (after this, a new incisional biopsy was repeated to have a confirmatory diagnosis of no dysplasia).

All patients gave informed consents. The study was conducted according to the principles of the Helsinki Declaration of 1975, as revised in 2000.⁶

Sample size was difficult to estimate because of the lack of earlier data; it was calculated, for a range of values at 0.95 confidence, for a 56 × 2 sample size (with software PASS13^®). Both groups finally constituted 56 lesions.

The primary outcome was the healing of the lesion after surgical treatment; the secondary outcome was the onset of an oncological lesion. Descriptive analyses were performed using the t-test and the Fischer exact test for calculated variables, setting the statistical significance level at 0.05.

SPSS (SPSS for windows, version 19; SPSS, Inc, Chicago, IL) statistical software was utilized.

Results

Initially 108 subjects were selected: 12 of these were excluded because showing exclusion criteria (8 had dysplastic lesion, 3 presented a neoplastic lesion, and 1 was found to be pregnant after first biopsy); 9 refused to be part of this study. Eighty-seven patients were finally included (mean age, 66.83 ± 9.98 years), of which 47 were women (54.02%). The average age at diagnosis was 67.58 years for females and 66.22 for males.

One hundred seventeen lesions were treated. Fifty-eight lesions underwent surgery with traditional scalpel, whereas 59 were treated using laser. No statistical differences were detailed between the two groups regarding size and site of involvement, gender, age, and smoking habits (Table 1).

Table 1.

Comparison Between Group A_TrSc (Scalpel) and Group B_Las (Laser), Considering All the Lesions (n = 117)

	Group A_TrSc	Group B_Las	p
Baseline
n ^a of treated lesions	58	59	0.943^*
Female, % (n ^a)	55.55% (25)	61.90% (26)	0.514^*
Age (year), mean ± SD	68.96 ± 13.41	65.89 ± 11.91	0.201^*
Smokers, % (n ^a)	24.44% (11)	23.80% (10)	0.911^*
Lesions >1 cm, % (n ^a)	34.48% (20)	38.98% (23)	0.869^*
Lesions <1 cm, % (n ^a)	65.52% (38)	61.01% (36)	0.920^*
Gingiva, % (n ^a)	37.93% (22)	44.07% (26)	0.792^*
Palate, % (n ^a)	3.45% (2)	6.78% (4)	0.727^*
Buccal mucosa, % (n ^a)	44.83% (26)	32.20% (19)	0.447^*
Tongue, % (n ^a)	13.79% (8)	16.95% (10)	0.881^*
Recurrences^a
Total, % (n ^a/total number)	43.10% (25/58)	50.84% (30/59)	0.454^†
Lesions >1 cm
% (n ^a/number at baseline)	80% (16/20)	91.30% (21/23)	0.940^*
Lesions <1 cm
% (n ^a/number at baseline)	23.68% (9/38)	25% (9/36)	>0.99^*
Gingiva
% (n ^a/number at baseline)	45.45% (10/22)	53.85% (14/26)	0.930^*
Palate
% (n ^a/number at baseline)	50% (1/2)	50% (2/4)	1^*
Buccal mucosa
% (n ^a/number at baseline)	38.46% (10/26)	52.63% (10/19)	0.750^*
Tongue
% (n ^a/number at baseline)	50% (4/8)	40% (4/10)	>0.99^*

At the end of the follow-up period.

t-Test.

†

Fischer exact test.

TrSc, traditional scalpel.

Follow-up ranged from 24 to 108 months (median of 58); visits were scheduled every 6 months. Healing was detailed for 52.99% (n = 62) of the 117 OL, with no statistical differences between the two randomized groups (Table 1); no differences were also detailed in terms of differences in site of involvement and in reported size of the lesions (Table 1).

During the follow-up period, none of the patients developed an oncological oral event, and no reported complications were observed. Moreover, the wound healing process after the two proposed treatments was satisfactory and no significant complications were observed.

Discussion

To the best of our knowledge, a long-term assessment between Er:YAG laser and traditional scalpel has never been performed regarding surgical management of OL. As said, we had identified statistical difference during the initial postoperative period between the two treatments: Er:YAG laser seemed to be less painful, and patients also seemed to prefer it, especially when having a bigger lesion in the gingival or in the palate.

It seems reasonable to consider the Er:YAG laser as effective as traditional scalpel in terms of healing for OL. The two methods did have the same rate of recurrences in a period of almost 5 years. These data have never been reported previously.

One of the main limitations of this type of laser is when it is used in the ablative mode, because it is impossible to obtain an histopathological specimen; for this reason, we have considered only homogeneous white lesion, having a risk of dysplastic alteration less than 10%.^1,2 In the follow-up period if a recurrence was noted a new confirmatory biopsy was undertaken to obtain the similar result of no dysplasia. If a dysplastic change was noted, the conventional surgical excision was performed.

Laser technology could offer different advantages during both intraoperative and postoperative sessions: hemostatic antimicrobial effect improved healing of the wounds and reduction of pain and edema.^8,9

Surgical properties of Er:YAG lasers in oral surgeries have been detailed, reporting good cutting and coagulation effects, with minimal tissue damage and low inflammatory damage, and also a quicker healing process.⁸ Considering our data, it is also possible to add its value for the long-term stability of immediately postoperative results obtained. In addition, very recently it has been reported that the use of Er:YAG laser in OL patients gave a significantly better outcome than the use of traditional scalpel in OL patients.⁹

Our reported recurrence rate is higher than that reported in the literature (e.g., 40%), but this study population have been treated without bearing in mind the new paradigm of always considering a minimal resection margin of 3 mm to obtain a minimal recurrence rate.^9,10 This should always be considered especially when using the Er:YAG laser, which can be particularly difficult to use correctly in the marginal border of the lesions. However. The Er:YAG laser produces a rapid healing as a result of the limited later thermal effect generated. An inconvenience, nevertheless, is that the surgical field is not free of blood (unlike with the CO₂ laser); subsequently, upon finishing surgery session, firmness of the treatment zone is required to ensure suitable hemostatic effect. The Er:YAG laser, in fact, has been reported to be slightly inferior to other lasers,⁴ with a slightly worse bleeding, making the margin of the lesion more difficult to comprehend during resection.

In conclusion, these results, although not categorical, are more of a step forward for enhanced management of this condition. It would also be interesting to know if this statement will be the same with a greater number of patients or in a different clinical setting.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

. Warnakulasuriya

, Johnson

, van der Waal

. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med, 2007; 36:575–580.

. van der Waal

. Potentially malignant disorders of the oral and oropharyngeal mucosa; present concepts of management. Oral Oncol, 2010; 46:423–425.

. Ishikawa

, Aoki

, Takasaki

. Clinical application of erbium:YAG laser in periodontology. J Int Acad Periodontol, 2008; 10:22–30.

. Romeo

, Libotte

, Palaia

, et al. Histological in vitro evaluation of the effects of Er:YAG laser on oral soft tissues. Lasers Med Sci, 2012; 27:749–753.

. Onisor

, Pecie

, Chaskelis

, Krejci

. Cutting and coagulation during intraoral soft tissue surgery using Er:YAG laser. Eur J Paediatr Dent, 2013; 14:140–145.

. Broccoletti

, Cafaro

, Gambino

, Romagnoli

, Arduino

. Er:YAG laser versus cold knife excision in the treatment of non-dysplastic oral lesions: a randomized comparative study for the postoperative period. Photomed Laser Surg, 2015; 33:604–609.

. Arduino

, Surace

, Carbone

, et al. Outcome of oral dysplasia: a retrospective hospital-based study of 207 patients with a long follow-up. J Oral Pathol Med, 2009; 38:540–544.

. Seoane

, González-Mosquera

, López-Niño

, et al. Er,Cr:YSGG laser therapy for oral leukoplakia minimizes thermal artifacts on surgical margins: a pilot study. Lasers Med Sci, 2013; 28:1591–1597.

. Monteiro

, Barbieri

, Warnakulasuriya

, et al. Type of surgical treatment and recurrence of oral leukoplakia: a retrospective clinical study. Med Oral Patol Oral Cir Bucal, 2017; 22:e520–e526.

10.

. Kuribayashi

, Tsushima

, Sato

, Morita

, Omura

. Recurrence patterns of oral leukoplakia after curative surgical resection: important factors that predict the risk of recurrence and malignancy. J Oral Pathol Med, 2012; 41:682–688.