Ear, Nose & Throat Journal2023, Vol. 102(3) 170–174© The Author(s) 2021Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/0145561321989437journals.sagepub.com/home/ear
Objectives: This study aimed to identify vocal fold leukoplakia (VFL) lesions on the inferior surface as a risk factor for recurrence. Methods: This was a retrospective study with data collected from 2001 to 2018. The study comprised 37 patients with VFL, divided into the nonrecurrent and recurrent groups. We examined the clinicopathological characteristics and the surgical procedures performed in each patient. Results: Among the 37 patients, 15 (40.5%) had residual (3) or recurrent (12) VFL. Of those patients with and without recurrence, 8 of 12 (66.7%) and 6 of 22 (27.3%), respectively, had inferior surface lesions of the vocal fold at the initial operation (P = .036). Recurrences were significantly higher in patients with inferior surface lesions. Other evaluated factors did not show significance for recurrence. Conclusion: The presence of VFL lesions on the inferior surface is a significant risk factor for recurrence.
Keywordslaryngeal lesions, laryngoscopy, leukoplakia, microsurgery, recurrence, vocal fold
Vocal fold leukoplakia (VFL) is clinically described as a white epithelial lesion. The incidence is generally higher in males than in females, with 10.2 and 2.1 lesions per 100,000, respectively, and peaks at 45 to 64 years.1 Vocal fold leukoplakia resection is performed using cold instruments and lasers, depending on the risk of malignant transformation. The ability to accurately predict VFL recurrence is challenging and postoperative recurrence remains a matter of concern.2-6 Treatment protocols to prevent recurrences have not yet been established.
Reported risk factors for recurrent VFL include alcohol consumption, smoking, gastroesophageal reflux, the site and size of the lesion, and the pathological grade of the initial lesion.7-10 However, there are discrepancies in the literature regarding certain factors, specifically smoking and alcohol consumption, being associated with higher rates of recurrence.7-10 Moreover, the recurrence risks associated with the pathological grade and site and size of the lesion remain controversial.4,7,9-11 The risk of recurrence with lesions on the inferior surface of the vocal fold has not been examined. The aim of this preliminary study was to assess the association of inferior surface lesions with recurrent VFL.
This study was approved by the institutional ethical committee in Tokyo, Japan (20190903), and registered in the University Hospital Medical Information Network (ID: R000045002). A retrospective review was performed to evaluate data from 37 patients with VFL treated at our institution with cold instrument resection or in conjunction with a holmium yttrium aluminum garnet (Ho: YAG) laser (2100 nm, pulse energy 0.2 J, repetition rate 5 Hz, VersaPulse PowerSuite 100 W, Lumenis Ltd) from January 2001 to December 2018 (Table 1). An initial laryngoscopy clinically diagnosed white lesions of the vocal fold as VFL. Surgery was performed on patients whose lesions lacked smooth vocal fold edges, as indicated by stroboscope vibration waves.
The patients were divided into 2 groups (Table 2): with recurrence (appearing 6 months after treatment) and without recurrence.12 Participants with residual disease (appearing within 6 months) were excluded. The clinical characteristics, sex, age, alcohol consumption, smoking, presence of laryngopharyngeal reflux disease (LPRD), site and size of the lesion (length of the lesion relative to the total length of the vocal fold membrane), the lesions of the inferior surface and anterior commissure, difficult laryngeal exposure (DLE), and pathological grade were individually compared between the groups.
Written informed consent was given by all patients. An in-office laryngoscopy was performed before surgery using a strobe digital system. Video recordings were preserved and reviewed during each follow-up visit. Surgeries were performed under general anesthesia using a Saito direct laryngoscope (Nagashima Medical Instruments Co, Ltd) and a microscope. In 9 patients, the lesions were microsurgically resected using cold instruments in the initial surgery. In 28 patients, a portion of the lesion was microsurgically resected for biopsy using cold instruments, and residual lesions were treated with Ho: YAG laser to vaporize only the epithelium through noncontact irradiation, with a distance of 1 to 4 mm between the lesion and the laser fiber tip. Inferior surfaces were visualized with a fiberscope during surgery and vaporized using laser. The lesions of the inferior surfaces were diagnosed during surgery by maneuvering and inverting the superior surface of the vocal fold to reveal the inferior surface (Figure 1). Difficult laryngeal exposure was diagnosed when the entire lesion could not be observed with the smallest sized laryngoscope. Anterior commissure lesions were observed with a fiberscope and attempted to be vaporized using laser. Postoperative follow-ups were performed every 1 to 3 months for a minimum of 1 year. During every visit in the postoperative follow-up period, we made sure to assess lesions on the vocal folds’ inferior surface by subjecting them to close scrutiny with a fiberscope for a complete examination.
The histopathological results were graded by 2 pathologists as no dysplasia, mild dysplasia, moderate dysplasia, or severe dysplasia, in accordance with the World Health Organization classification.13
Statistical analysis was conducted using Fisher exact test. The odds ratio (OR) and 95% CIs for each risk factor were calculated using a 2-tailed test of significance. Statistical analysis was performed using GraphPad Prism version 6.04 for Windows (GraphPad Software). Data analyzed by descriptive statistics are presented here. Univariate analyses of the postoperative recurrence and potential significant clinical factors were tested. Statistical significance was defined as 2-sided P values <.05.
The total number of patients was 37 (Table 1), with 35 men (94.6%) and ages ranging from 32 to 84 years (mean age: 64.6 ± 9.8 years). Twenty-seven (73.0%) patients consumed alcohol and 30 (82.4%) had a smoking habit. Laryngopharyngeal reflux disease was prevalent in 15 (40.5%) patients. Thirteen (35.1%) patients had bilateral lesions, with 15 (40.5%) having lesions involving more than 50% of the vocal fold surface. The lesions of the inferior surfaces were present in 16 (43.2%) patients. The lesions of the anterior commissure were present in 4 (10.8%) and DLE in 5 (13.5%) patients. The most common histopathological finding at the initial biopsy was mild dysplasia (10 patients, 27.0%).
The clinical characteristics, sex (P = .16), age (P = 1.0), alcohol consumption (P = 1.0), smoking (P = .63), presence of LPRD (P = .45), site of the lesion (P = 1.0), size of the lesion (P = .71), anterior commissure (P = .6), DLE (P = 1.0), and pathological grade (P = 1.0) were not significant risk factors for recurrence.
Among the 37 patients, 15 (40.5%) had residual (3) and recurrent (12) VFL. Of the 12 patients with VFL recurrence, 8 (66.7%) had lesions on the inferior surface (Table 2). Of these 8 patients, 6 (75%) had a recurrence of inferior surface lesions. Of the four VFL recurrences without the lesions on the inferior surfaces, 1 (25%) had recurrence of the inferior surface lesion. In the nonrecurrent group, 6 out of 22 patients (27.3%) had the lesions on the inferior surface. Thus, lesions of inferior surfaces were identified as a significant risk factor for recurrent VFL (P = .036, OR: 5.3, 95% CI: 1.2-24).
Follow-up after surgery ranged from 12 to 104 months (mean, 34 ± 26 months) and 35 to 123 months (mean, 68 ± 24.5 months) in the nonrecurrent and recurrent groups, respectively. Recurrence was seen from 10 to 53 months (mean, 20 ± 11 months) of the follow-up period. One patient developed carcinoma in situ (2.7%) after 49 months and another had invasive squamous cell carcinoma (2.7%) within 24 months.
Recurrence after VFL surgery is a great concern for patients and surgeons. The reported recurrence rates after surgery, including our study results, are high and with a wide range (9.5%-46.4%).4-6,9,11 Moreover, recurrence leads to an increased malignant transformation rate, a shorter time interval to develop squamous cell carcinoma, and scarring and dysphonia in the vocal folds due to repeated surgery.14 Different excisional and ablation options for VFL include cold instrument resection, carbon dioxide laser, potassium-titanyl-phosphate laser, and pulsed dye laser.15-20 However, there are no significant differences in recurrence prevention between these methods.
Physicians have previously focused on the roles of sex, age, and lifestyle habits such as alcohol consumption and smoking as risk factors in VFL recurrence.4,7-10 In this study, alcohol consumption, smoking, LPRD, and site and size of lesion were not found to be significant risk factors. However, the limited impact of the study’s small sample size must be taken into account when interpreting the results. Moreover, these factors are not physician related.
In-office surgeries, commonly performed nowadays for vocal fold diseases, have not affected the recurrence and malignant transformation rates in VFL.21 Hu et al reported that VFL recurrence in the inferior surfaces occurred in 2 out of 11 patients.20 In our study, lesion recurrence occurred in the inferior surface in 6 (75%) of 8 patients, whereas lesion recurrence in the inferior surface without primary inferior surface lesions occurred in 1 (25%) of 4 patients.
The follow-up period was an important factor for estimating the recurrence rate. The mean duration for recurrence is 16 to 24 months, with a follow-up period of 32 to 109 months.7,11,14,22-24 Here, the mean recurrence time was 20 months, and the follow-up period in the recurrent group was 68 months. Although the mean follow-up for nonrecurrent patients was 34 months, some cases did not have enough follow-up time to be affected by recurrence. Therefore, a follow-up period of at least 2 years seems to be necessary.
Apart from the small sample size, the retrospective nature is also a limitation of this study. Additionally, the procedures were performed by multiple surgeons, and variations in surgical methods could impact the results. A prospective study with a larger sample size is warranted.
In this study, the lesions of inferior surface of the vocal fold were a significant risk factor for recurrent VFL.
We would like to thank Editage (www.editage.com) for English language editing.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Hisashi Hasegawa https://orcid.org/0000-0002-3111-6300
1 Department of Otolaryngology–Head and Neck Surgery, Nihon University School of Medicine, Tokyo, Japan
Received: August 11, 2020; revised: December 13, 2020; accepted: January 3, 2021
Corresponding Author:Hiroumi Matsuzaki, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Nihon University School of Medicine, 1-6 Kandasurugadai, Chiyoda-ku, Tokyo 173-8610, Japan.Email: matuzaki.hiroumi@nihon-u.ac.jp
