Recurrence and malignant transformation of laryngeal leukoplakia treated with CO2 laser: A systematic review and meta-analysis.

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

Long-term outcomes of aminolevulinic acid photodynamic therapy for treatment of recalcitrant laryngeal premalignant lesions.

OBJECTIVE: To assess long-term outcomes of ALA-PDT in treating recalcitrant laryngeal leukoplakia. STUDY DESIGN: Retrospective Case-Control. METHODS: We reviewed all laryngeal leukoplakia patients treated with ALA-PDT compared with angiolytic laser treatment alone (585 nm PDL or 532 nm KTP laser) from 2000 to 2019. Patients with laryngeal cancer (or a history of laryngeal cancer), leukoplakia previously treated with radiation and no pathologic report were excluded. Patient demographics, procedure details and outcomes were examined including histopathologic diagnosis, procedures performed, ALA usage, recurrence of leukoplakia and the development of cancer. RESULTS: We identified 132 patients with laryngeal leukoplakia: 42 were treated with ALA-PDT and 90 were treated with an angiolytic laser alone (Laser group). The proportion of cases of high-grade dysplasia was 57.1% in the ALA-PDT group compared to 32.2% in the Laser group. In high-grade dysplasia cases, there was a statistically significant better recurrence-free survival (RFS) at 12 months and 60 months in those who underwent ALA-PDT 71.4% and 7.1% vs Laser 25% and 0% (p = .01). However, for overall groups, there was no difference in RFS (p = .25). Voice outcomes (patient subjective report) improved or were stable in 75% of subjects with no serious side effects reported. CONCLUSION: ALA-PDT for recalcitrant and high-grade dysplasia is highly effective with improved recurrence-free survival compared to laser alone. ALA-PDT may be an appropriate therapy in patients who have failed prior angiolytic laser alone.

Comparing suspension laryngoscopic mucosal dissection and plasma resection for laryngeal leukoplakia: prognostic outcomes.

OBJECTIVE: The current research was designed to compare the clinical efficacy of suspension laryngoscopic mucosal dissection and plasma resection in the management of laryngeal leukoplakia and their effects on patient prognosis. METHODS: Retrospective analysis was conducted on 184 laryngeal leukoplakia patients treated in Ningbo Beilun People's Hospital from January 2018 to October 2021. Based on the inclusion and exclusion criteria, 128 eligible patients were included, including 64 patients who underwent suspension laryngoscopic mucosal dissection (control group) and 64 patients who underwent cryolyrectomy (study group). The operative time, intraoperative bleeding volume, and time of pseudomembrane detachment in the two groups were recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the serum concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon-γ (IFN-γ), and IL-17A at 24 hours after surgery. Postoperative follow-up was conducted for one year. Results of the noise acoustic testing and stroboscopic laryngoscopy, including noise/harmonic ratio, amplitude perturbation, fundamental frequency perturbation, vocal fold vibration symmetry, and vocal fold mucosal wave, were documented before treatment and three months after treatment. The cumulative recurrence rate of patients within one year after surgery was recorded, and the cumulative recurrence rate of patients within 1 year after surgery was compared between the two groups. RESULTS: Cryo-plasma resection significantly contributed to shorter operative time and less intraoperative bleeding volume as compared with suspension laryngoscopic mucosal dissection (both P<0.05), while time-lapse before postoperative pseudomembrane detachment was similar between the two groups (P>0.05). Patients with cryo-plasma resection exhibited significantly milder postoperative inflammatory response than those with suspension laryngoscopic mucosal dissection, as evinced by the lower serum concentrations of IL-2, IL-6, TNF-α, IFN-γ and IL-17A at 24-h in patients with cryo-plasma resection after operation (P<0.05), while the levels of IL-4 and IL-10 were similar between the two groups (P>0.05). At 3 months after operation, cryo-plasma resection contributed to more significant reductions of noise/harmonic ratio, amplitude perturbation, fundamental frequency perturbation, vocal fold vibration symmetry, and vocal fold mucosal as compared with suspension laryngoscopic mucosal dissection (P<0.05). Cryo-plasma resection contributed to a significantly lower incidence of cumulative recurrence than suspension laryngoscopic mucosal dissection (P<0.05). Multivariate analysis revealed no statistical difference in the impact of gender, age, smoking, and alcohol consumption on the recurrence and malignant transformation of laryngeal leukoplakia (P>0.05). CONCLUSION: Both suspension laryngoscopic mucosal dissection and plasma resection can provide significant efficacy in the treatment of laryngeal leukoplakia, and cryo-plasma resection can contribute to a lower incidence of relapse, enhanced postoperative recovery, and superior short- and long-term outcomes than plasma resection.

Office-Based Photodynamic Therapy Using Locally Applied 5-aminolevulinic Acid and 635 nm Laser for Laryngeal Leukoplakia.

OBJECTIVE: Photodynamic therapy (PDT) is a minimally invasive method with strong tissue selectivity and nonthermal effects. We aim to investigate the efficacy of an in-office method utilizing PDT with local application of 5-aminolevulinic acid (ALA) and 635 nm diode laser for treating laryngeal leukoplakia. STUDY DESIGN: Retrospective cohort study. SETTING: Outpatient clinic-tertiary medical center. METHODS: This study reviewed 32 patients with laryngeal leukoplakia, including 11 recurrent cases after surgery. All the procedures were performed in an office setting under topical anesthesia. Fifteen percent ALA solution was locally applied to the lesion through a flexible laryngoscope. Light illumination was performed using a 635 nm diode laser through a 400 µm optic fiber. The power density was 165 mW/cm2 to reach 100 J/cm2 . Results of laryngostroboscopy and voice evaluation during follow-up were collected. RESULTS: The mean follow-up was 7.91 ± 4.83 (3-18) months. Thirty-nine procedures were performed, including 1 session for 27 patients, 2 sessions for 3 patients, and 3 sessions for 2 patients. The total response rate was 96.875% (31/32), including complete responses in 26 (81.25%) patients, partial responses in 5 patients (15.625%), and no response in 1 patient (3.125%). It appeared that PDT selectively eliminated the leukoplakia without affecting lamina propria and the surrounding normal mucosa remained unharmed. Scores of Voice Handicap Index-10, jitter, shimmer, and harmonic-to-noise ratio were significantly improved after PDT. CONCLUSION: Office-based PDT is an effective, repeatable, and practical method for treating laryngeal leukoplakia. Local application of ALA is sufficient to achieve photodynamic reactions. PDT could eliminate laryngeal leukoplakia selectively while protecting the normal laryngeal structure.

Malignant Transformation and Long-Term Outcome of Oral and Laryngeal Leukoplakia.

BACKGROUND: Oral or laryngeal leukoplakia has an increased risk for malignant transformation but the risk of the two anatomical sites has not been compared to each other yet. MATERIALS AND METHODS: Clinical data of 253 patients with leukoplakia (oral = 221 or laryngeal = 32) enrolled from January 1996 to January 2022 were analyzed. One hundred and seventy underwent biopsy and 83 did not. The mean follow-up time was 148.8 months. Risk factors for the malignant transformation of leukoplakia were identified using Cox proportional hazard models. RESULTS: In the oral or laryngeal group, the rate of cancer was 21.7% and 50% (p = 0.002), respectively. The 10-year estimated malignant transformation was 15.1% and 42% (p < 0.0001), respectively. The laryngeal group had an increased risk of malignant transformation (p < 0.0001). The 5-year estimated survival with leukoplakia-associated cancer for the oral or laryngeal group was 40.9% and 61.1% (p = 0.337), respectively. Independent predictors of malignant transformation in the oral group were dysplasia and the grade of dysplasia of the leukoplakia, and in the laryngeal group, dysplasia had a significant impact. The malignant transformation rate was low for oral patients without biopsy or with no dysplasia, 3.9% and 5.1%, respectively. The malignant transformation occurred over 10 years. CONCLUSIONS: Patients with dysplastic leukoplakia have an increased risk of malignant transformation, but the risk is higher with laryngeal than with oral leukoplakia. There is no significant difference between the groups regarding survival with leukoplakia-associated cancer. Oral patients with no dysplastic lesions have a low risk of malignant transformation. A complete excision and long-term follow up are suggested for high-risk patients to diagnose cancer in an early stage and to control late (over 10 years) malignant events.

Successful treatment of laryngeal leukoplakia by photodynamic therapy with local application of 5-aminolevulinic acid and 635 nm laser: A case report.

Laryngeal leukoplakia is a common disorder in otolaryngology. Presently, the most widely accepted treatment is suspension laryngoscopic surgery under general anesthesia. The high recurrence rate and hoarse voice after surgery make it an intractable disease to treat. Here we report a case of a 67-year-old man who was diagnosed of laryngeal leukoplakia 15 years ago and underwent 5 surgeries because of its repeated recurrences. Two sessions of photodynamic therapy were performed with local application of 5-aminolevulinic acid and irradiation of 635 nm diode laser. Complete response was observed and no recurrence was detected during follow-up of 6 months. Photodynamic therapy with local 5-ALA application and 635 nm laser is safe and well-tolerated. It is a promising modality for laryngeal leukoplakia.

Preliminary dynamic observation of wound healing after low-temperature plasma radiofrequency ablation for laryngeal leukoplakia.

BACKGROUND: Low-temperature plasma ablation (LTPA) is an emerging technique for laryngeal leukoplakia (LL). OBJECTIVE: To initially observe the healing process of trauma after LTPA for LL. MATERIALS AND METHODS: Seventeen patients who underwent LTPA for LL were collected, and the degrees of wound healing were analyzed. RESULTS: Only 1 patient in who dysbiosis of the pharyngeal flora was induced by self-administered hormone nebulization treatment during the follow-up period. In the remaining patients, the wound healing was characterized by a crater-shaped defect on the vocal folds surface with pseudo-membranes, congestion, and mild edema on postoperative day 1. These symptoms became worse on postoperative day 7. On postoperative day 15, the pseudo-membrane was fully formed and some patients had granulomatous swelling of the vocal cords. These symptoms became better and better on postoperative day 30 and day 45. On postoperative day 60, the mucosa of the vocal folds had essentially returned to normal. On postoperative day 90, the vocal folds morphology and function had recovered well. CONCLUSION: It takes 2-3 months for the wound to heal completely after LTPA for LL. SIGNIFICANCE: A proper understanding of the wound healing process can reduce unnecessary surgical and pharmacologic interventions and avoid excessive treatment.

[Application of deep learning assisted electronic laryngoscope in diagnosis of laryngeal leukoplakia].

In recent years, medical imaging technology and computer technology have made great progress. On the one hand, with the development and popularization of electronic laryngoscope, the image of electronic laryngoscope plays a very important role in the diagnosis of vocal cord lesions. On the other hand, deep learning algorithm，especially convolutional neural networkhas gradually become the first choice of medical image recognition since the foundation of deep learning algorithm. So far, deep learning algorithm has made great contributions in many disciplines. In this paper, the basic concept of deep learning, the current status of image recognition of vocal cord lesions, and the prospect of research based on deep learning in vocal cord image lesions recognition are reviewed.

Quantification of Vocal Fold Vibration in Various Laryngeal Disorders Using High-Speed Digital Imaging.

OBJECTIVE: To quantify vibratory characteristics of various laryngeal disorders seen by high-speed digital imaging (HSDI). METHODS: HSDI was performed on 78 patients with various laryngeal disorders (20 with polyp, 16 with carcinoma, 13 with leukoplakia, 6 with vocal fold nodule, and 33 with others) and 29 vocally healthy subjects. Obtained data were quantitatively evaluated by frame-by-frame analysis, laryngotopography, digital kymography, and glottal area waveform. RESULTS: Overall, patients with laryngeal pathologies showed greater asymmetry in amplitude, mucosal wave and phase, smaller mucosal wave, and poorer glottal closure than vocally healthy subjects. Furthermore, disease-specific vibratory disturbances that generally agreed with the findings in the literature were quantified: comparing polyp with nodule, differences were noted in longitudinal phase difference, amplitude, and mucosal wave. In comparison with leukoplakia and cancer, nonvibrating area was more frequently noted in cancer. CONCLUSIONS: The HSDI analysis of various voice disorders using multiple methods can help phonosurgeons to properly diagnose various laryngeal pathologies and to estimate the degree of their vocal disturbances.

Clinicopathological Analysis of Laryngeal Leukoplakia: Clinical Follow-up and Immunohistochemical Expression of p53 and PCNA

Laryngeal leukoplakia is seen in a number of pathologic settings such as keratosis without atypia(KWOA), keratosis with atypia(KWA), squamous cell carcinoma in situ(CIS) and invasive squamous cell carcinoma, and it continues to be a confusing and controversial topic for both otolaryngologist and pathologist. This is largely due to the use of ambiguous and inconsistent terminology, the lack of unanimous agreement on the definition of these terms, failure of the clinician to obtain a representative biopsy, and the subjectivity of the pathologist interpreting the biopsy. To evaluate the applicability of the expression pattern of p53 and PCNA in borderline cases of histopathologic classification, we performed a histopathologic analysis of leukoplakia to includ clinical follow-up, correlation of disease progression and degree of atypia, and expression of p53 and PCNA according to the degree of atypia. Histologically, laryngeal leukoplakia included seven cases of KWOA, fourteen cases of KWA (mild-2, moderate-8, severe-4), three cases of CIS, and one case of invasive squamous cell carcinoma. Keratosis with atypia, a moderate degree or more, showed a strong tendency to progress to invasive carcinoma(p<0.05). The degree of p53 and PCNA expression correlated with the degree of atypia(p<0.05). p53-positive cases at the initial biopsy clearly tended to recur and develop into invasive carcinoma(p<0.01).