Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia.

PURPOSE: The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms. METHODS: Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red. RESULTS: It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells. CONCLUSION: It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

Endoscopic diagnosis value of narrow band imaging Ni classification in vocal fold leukoplakia and early glottic cancer.

OBJECTIVES: To explore the diagnostic value and the correlation between histological diagnosis and the Ni classification under narrow band imaging (NBI) for vocal fold leukoplakia (VFL) and early glottic cancer. METHODS: A total of 91 patients with 119 vocal fold lesions were selected from January 2017 to May 2020. All these patients were subsequently examined by white light imaging (WLI) and NBI endoscopy, and then all lesions were classified by the Ni classification according to the characteristics of intraepithelial papillary capillary loop (IPCL) observed. The gold standard of diagnosis was histopathological results. Eventually, the chi-square and kappa test were applied, respectively, to evaluate the diagnostic value of NBI endoscopy and the consistency of Ni classification and pathological results. RESULTS: The accuracy and sensitivity of NBI endoscopy were significantly higher than that of WLI endoscopy (P < 0.05). For the diagnosis of precancerous lesions under the NBI, the sensitivity, specificity, positive and negative predictive value were 69.6% (16/23), 90.6% (87/96), 64.0% (16/25) and 92.6% (87/94), which for malignant lesions were 84.4% (65/77), 92.9% (39/42), 95.6% (65/68) and 76.5% (39/51). Moreover, for patients with low-grade intraepithelial neoplasia (mild and moderate dysplasia), type IV lesions accounted for the most (69.6 vs 30.4%; χ2 = 36.961, P < 0.001). For high-grade intraepithelial neoplasia or carcinoma in situ, type Va lesions were predominant (χ2 = 30.526, P < 0.001), while type Vb and Vc lesions were dominant in invasive carcinoma (χ2 = 64.373, P < 0.001). Besides, the kappa test revealed that there was a high consistency between Ni classification and pathological diagnosis (Kappa = 0.667, P < 0.001). CONCLUSIONS: The Ni classification can improve the diagnosis accuracy of vocal fold lesions which enables clear visualization of mucosal microvasculature. This is essential for the early diagnosis of VFL and early glottic cancer during routine endoscopic examination.

Association between Laryngopharyngeal Reflux and Vocal Fold Leukoplakia.

INTRODUCTION: Vocal fold leukoplakia (VFL) has a risk of malignant transformation, and the underlying mechanisms are currently unrecognized. Some clinical evidence has indicated that laryngopharyngeal reflux (LPR) probably plays a critical role. OBJECTIVE: To explore the risk factors associated with the occurrence of VFL and to investigate the importance of LPR in VFL and its different pathological types using 24-h multichannel intraluminal impedance-pH monitoring. MATERIALS AND METHODS: Eighty-one patients with VFL and 27 healthy volunteers were recruited. General information and LPR parameters were analyzed. RESULTS: The monitoring showed that 35.8% (29/81) of patients had acidic LPR and that 43.2% (35/81) had weakly acidic LPR. Heavy drinking (odds ratio = 4.004, p = 0.037) and acidic LPR (odds ratio = 4.471, p = 0.029) were independent risk factors for the occurrence of VFL. Acidic LPR showed a strong correlation with the Reflux Finding Score (p < 0.05) in patients suspected of having LPR based on the scale score. Meanwhile, weakly acidic LPR parameters increased with the severity of pathological degrees which were higher in high-grade dysplasia (p < 0.05). CONCLUSION: Our study confirms the importance of LPR in VFL. Heavy drinking patients with VFL, particularly those with acidic LPR, should undergo intensive treatment. Meanwhile, weakly acidic LPR may play a critical role in the pathological changes in VFL.

Elevated peripheral inflammatory markers are related with the recurrence and canceration of vocal fold leukoplakia.

OBJECTIVE: To evaluate the predictive value of preoperative peripheral inflammatory markers in patients with vocal fold leukoplakia. METHODS: A retrospective study was performed of the patients diagnosed with vocal fold leukoplakia and who accepted carbon dioxide (CO2) laser resection in our center in the last 10 years. We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) after collecting and analyzing the clinical, histopathological and laboratory data. The potential relation between blood indexes and clinical events as recurrence or canceration was evaluated. RESULTS: A total of 589 patients were involved, including 300 cases without recurrence (group A), 198 with recurrence but not canceration (group B) and 91 transformed into squamous cancer (group C). Baseline analysis of NLR, PLR, and MLR showed no difference among the three groups before the first surgery. But all the indexes significantly elevated in groups B (P < 0.001, < 0.001, 0.023, respectively) and C (P = 0.009, 0.004, 0.007, respectively) in the last operation. The receiver-operating curve (ROC) analysis showed NLR as a potential marker of canceration of leukoplakia (AUC = 0.837) and the cutoff value was 2.505. When regrouping with pathological outcomes, severe dysplasia and squamous cell carcinoma (SCC) groups both revealed a higher level of NLR, PLR, and MLR comparing to the no dysplasia, mild dysplasia, and moderate dysplasia groups. NLR, PLR, and MLR in high-risk group (moderate, severe dysplasia and carcinoma) also elevated comparing to low-risk group (no dysplasia, mild dysplasia) (P = 0.039, 0.011, 0.007, respectively). CONCLUSIONS: The peripheral inflammatory markers NLR, PLR, and MLR are closely connected with the development of vocal fold leukoplakia. NLR may be a potential marker to predict the poor outcomes (recurrence or canceration) of patients in first surgery.

Recurrence of vocal fold leukoplakia after carbon dioxide laser therapy.

This work aims to analyze the recurrence of vocal fold leukoplakia after carbon dioxide (CO2) laser resection. In this retrospective study, all patients undergoing CO2 laser resection of vocal fold leukoplakia were followed up for at least 2 years. Recurrence was diagnosed as any presence of leukoplakia in the vocal cord subsequent to previous successful complete resection. A total of 326 patients with complete resection of vocal fold leukoplakia and follow-up subsequent surveillance laryngoscopy were studied. The recurrence rate, the recurrence time, and risk factors were evaluated. Of these, 52 (16.0%) patients experienced recurrence with a mean follow-up time of 50.5 ± 15.4 months. The mean time to recurrence was 16.2 ± 14.1 months. Univariate analysis showed that the size of lesion (P < 0.001, Pearson χ 2 test; P < 0.001, log-rank test) and the pathological grade (P = 0.025, Pearson χ 2 test; P = 0.028, log-rank test) were significantly related to recurrence. The size of lesion was an independent prognostic factor for recurrence using multivariate analysis (P = 0.001, logistic regression; P = 0.001, Cox proportional hazards model). Considering the possible recurrence of vocal fold leukoplakia, long-term follow-up is required after CO2 laser resection. In conclusion, the size of lesion combined with the pathological grade are important risk factors that predict vocal fold leukoplakia recurrence.

NBI Classification Optimization With Morphological Characteristics in Vocal Fold Leukoplakia.

Objectives: To investigate the pathological contribution of vocal fold leukoplakia (VFL) of type II in narrow-band imaging (NBI) classification and morphological characteristics to improve pathological prediction. Material and Methods: The 59 VFL patients with type II in 2019 Ni classification in NBI were included. The pathological reports were collected and divided following 2005 WHO Blue Book. Low-risk VFL contained non-, mild, moderate dysplasia, high-risk VFL included severe dysplasia. The morphological classification and laryngoscopic scoring system were employed to evaluate leukoplakia for pathological prediction. Results: The pathologies contained 1 case of leukoplakia with non-dysplasia, 12 of mild dysplasia, 15 of moderate dysplasia, 8 of severe dysplasia, and 23 of carcinoma. The 30 smooth VFL contained 1 non-dysplasia, 12 mild dysplasia, 14 moderate dysplasia, 2 severe dysplasia, and 1 carcinoma. The 29 rough cases included 1 moderate dysplasia, 6 severe dysplasia, and 22 carcinomas. Laryngoscopic scoring system revealed irregular texture, large size, and thick lesion as factors in relationship with high-risk leukoplakia in univariate (P = .002, <.001, <.001) and multivariate (P = .025, .002, .016) analysis, irregular texture was the most accurate predictor of high-risk VFL pathology. Conclusions and Significance: The pathologies of VFL with type II in NBI classification were hard to be predicted. Morphological irregular/rough texture contributed to predict high-risk pathology in leukoplakia.

Optimal Pathological Prediction of Vocal Fold Leukoplakia Based on IPCLs and Morphology.

OBJECTIVES: To establish a combined classification based on intrapapillary capillary loops (IPCLs) and morphological characteristics to improve the accuracy of pathological prediction of vocal fold leukoplakia (VFL). MATERIAL AND METHODS: A prospective research was conducted of VFL patients diagnosed by IPCLs and morphology. The VFL cases were classified as Type I-III based on IPCLs and morphological characteristics. Type I referred to VFL with dendritic vessels but not IPCLs. Type II defined VFL without any IPCLs or vessels and classified by morphology into two subtypes as non-rough Type IIa and rough Type IIb. Type III referred to VFL with IPCLs and classified into two subtypes as Type IIIa with small IPCLs and Type IIIb with large IPCLs or vascular distortion in or around lesions. Predicting pathology accuracy was analyzed. RESULTS: 182 eligible patients were recruited. The prediction accuracy rates of VFL pathology were 81.5% according to the 2019 Ni classification. The combined classification includes 4 cases of Type I, 28 Type IIa, 35 Type IIb, 56 Type IIIa, and 59 Type IIIb VFLs. The prediction accuracy rate of combined classification ranged from 95.1% to 97.3% in three observers. The average sensitivity, specificity, positive predictive value, negative predictive value was 97.8%, 86.2%, 97.4%, 88.2%, respectively. The inter-observer agreement varied from 84.1% to 94.0%, and mean area under curve of receiver-operating curve analysis was 0.954. CONCLUSIONS AND SIGNIFICANCE: The new combined classification based on IPCLs and morphological characteristics could predict pathology of VFL accurately. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Office-Based Blue Laser Therapy for Vocal Fold Leukoplakia: A Preliminary Report of 12 Cases.

Objective: To report the efficacy of office-based blue laser therapy for vocal fold leukoplakia. Study Design: A retrospective case series. Setting: A tertiary care center. Methods: A retrospective chart review of patients with vocal fold leukoplakia who underwent office-based blue laser therapy between July 2019 and October 2022 was conducted. The video recordings of their laryngeal examination and their voice evaluation were analyzed before and after surgical intervention. Results: A total of 10 patients, eight with unilateral disease and 2 with bilateral disease, were included in this study. In total, 12 vocal folds with leukoplakia were treated. Nine had a single session and 3 had 2 sessions due to incomplete regression of the lesion after the first laser therapy session. Following treatment, 9 regressed completely (75%) and 3 regressed partially (25%). The mean Voice Handicap Index-10 (VHI-10) score decreased significantly from 15.4 ± 12.9 preoperatively to 3.8 ± 2.86 after surgery (p = .023). There was a statistically significant decrease in the means of grade, roughness, breathiness, asthenia, and strain (p < .05). There was also a statistically significant decrease in the jitter and shimmer percent (p = .008 and p = .048, respectively) and a significant increase in the maximum phonation time from 9.63 ± 3.83 to 13.54 ± 5.92 seconds (p = .039). Conclusion: This preliminary study indicates that office-based blue laser therapy is an effective treatment modality for vocal fold leukoplakia.

Comparison Between Coblation and Microflap Resection of Leukoplakia of the Vocal Fold.

OBJECTIVES: The objective of this study was to compare the recurrence rate and voice improvement of vocal fold leukoplakia (VFL) between microflap resection alone or radiofrequency (RF) Coblation alone. METHODS: Patients with VFL intraoperatively treated via microflap resection alone or Coblation alone were enrolled. The recurrence rate, voice assessment, and Videostroboscopic images were compared between the two groups. RESULTS: The recurrence rate at postoperative 12 months was 37.7% (26/69) in the microflap resection group and 7.7% (4/52) in the Coblation group; the difference was significant (P < 0.05). The preoperative and postoperative subjective detection data from the two groups showed significant differences, but the Coblation group recovered better compared to the microflap resection group. No Coblation-related complications were found, including postoperative granulation tissue hyperplasia or anterior commissure adhesion. CONCLUSIONS: In patients with vocal cord leukoplakia, RF Coblation had a lower recurrence rate and better voice improvement compared with microflap resection.

Vocal fold fibroblasts promote angiogenesis in vocal fold leukoplakia by secreting pro-angiogenic factors.

OBJECTIVE: Cancer-associated fibroblasts (CAFs) have been reported to play an essential role in tumor angiogenesis and progression. In this study, we aimed to investigate the impact of vocal fold leukoplakia-associated fibroblasts (VFLFs) on the angiogenesis process in vocal fold leukoplakia (VFL) and their potential secretions of proangiogenic factors. METHODS: A total of 160 lesions (86 laryngeal carcinoma, 67 vocal fold leukoplakia, 7 vocal fold polyp) were detected under narrow band imaging (NBI) mode to evaluate the relationship between pathology and intraepithelial papillary capillary loop (IPCL) grades. We characterized immortalized vocal fold CAFs, VFLFs, normal fibroblasts (NFs) cell lines using immunofluorescence cytochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). The effects of fibroblast conditioned media (CM) on the proliferative, migrating and tube formation capacity of human umbilical vein endothelial cells (HUVEC) were investigated using the cell counting kit-8 (CCK-8) assay, wound healing assay, transwell migration experiment and Matrigel tube formation experiment. The expression levels of proangiogenic factors in CAFs, VFLFs, and NFs were evaluated by antibody microarray and RT-qPCR. RESULTS: NBI images depicted that angiogenesis was abnormally activated during laryngeal tumorigenesis. Both CAF and VFLF expressed Vimentin, alpha-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). NF expressed Vimentin and α-SMA, but not FAP. The PCR results showed that mRNA expression levels of Vimentin, α-SMA and FAP in CAFs and VFLFs were significantly increased than those in NFs. CAF-CM and VFLF-CM promoted the proliferative, migrating, and tube formation ability of HUVECs. Secretome profiling of fibroblasts by antibody microarray demonstrated that VFLFs secreted significantly more vascular endothelial growth factor (VEGF), angiogenin, bFGF and HGF than NFs. CONCLUSIONS: Overall, we demonstrated that VEGF, angiogenin, bFGF and HGF derived from VFLFs may play crucial roles in the angiogenesis process of laryngeal premalignant and malignant lesions. This may contribute to the exploitation of novel therapeutic strategies for VFL.

Cancer-associated fibroblast-like fibroblasts in vocal fold leukoplakia suppress CD8+T cell functions by inducing IL-6 autocrine loop and interacting with Th17 cells.

The characteristics of fibroblast cells in head and neck precancerous lesion and its ability to secrete inflammatory cytokines and affect CD8+T cell functions remain unclear. Herein, we reported the existence of fibroblasts in human-derived vocal fold leukoplakia (VFL) with positive staining of fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA). The fibroblasts from VFL and cancer-associated fibroblasts (CAFs) from head and neck squamous cell carcinoma (HNSCC) displayed similar cellular functions and robust inflammatory cytokine secretions. The effects of fibroblasts from VFL in inducing the apoptosis, depletion of CD8+ T cells and recruitment of regulatory T cells (Treg cells) were observed. We further assessed the autocrine loop within VFL fibroblasts to self-stimulate by secreting IL-6, TGF-ß through the IL-6/JAK2/STAT3 pathway. The synergistic stimulation of IL-6 and TGF-ß promoted Th17 cell differentiation and IL-17A secretion, which could result in fibroblast activation in another positive loop. Tocilizumab (TOC), a monoclonal antibody targeting IL-6R, managed to suppress the overexpression of both IL-6 and TGF-ß in VFL fibroblasts, and thus blocking IL-6 autocrine loop and CAF-Th17 loop in vitro. In a murine model of oral leukoplakia (OL), local injection of TOC inhibited the outgrowth of lesions and showed notable effect in control of OL progression in vivo. Our findings establish a novel rationale for blocking the IL-6/JAK2/STAT3 pathway to inhibit vocal fold (oral) leukoplakia progression and postpone HNSCC tumorigenesis.

Biomarkers for Malignant Potential in Vocal Fold Leukoplakia: A State of the Art Review.

OBJECTIVE: To explore biomarkers that are candidates for understanding potential degeneration to malignancy of vocal fold leukoplakia (VFL), with the goal of guiding future diagnostic and treatment recommendations. DATA SOURCES: PubMed and Medline search engines. REVIEW METHODS: A systematic review was conducted by searching the following key words: vocal fold or laryngeal, coupled with leukoplakia or dysplasia, and combined with the term prognostic markers. We collated the biomarkers and their significance, followed by observing the power of their evidence by assessing the quality of the studies according to guidelines of tumor marker prognostic studies (REMARK). CONCLUSIONS: Prognostic biomarkers in the 16 studies are generally divided into 3 categories according to their biological roles: proliferation (Ki-67, CK-1 RS14024 SNP), cell cycle control (P53, p16, cyclin D1, p57kip2, interleukin-10 [IL-10], miR-10a, and miR-34c), cell adhesion, and invasion (neutrophil-to-lymphocyte ratio, OPN/CD44v6 axis, MMP-1, vascular endothelial growth factor A, MMP-9, serpin peptidase inhibitor 1, plasminogen activator, CTNN/B1, ß-catenin, NANOG, HERG1). The prognostic use of these biomarkers is limited due to the variable methodologies, study design, assay methods, and statistical analysis performed. IMPLICATIONS FOR PRACTICE: Prognostic factors in vocal fold leukoplakia have important clinical implications regarding the potential for malignant degeneration. Although further study is needed, the currently available evidence suggests that p53, p16, cyclin D1, IL-10, NLR, OPN and CD44v6, CTNNB1, and CTTN and FAK might be of particular interest in determining prognosis of VFL as related to malignancy. Future, large, well-designed, prospective studies are expected to determine the prognostic power of these biomarkers before their implementation in routine clinical practice.

Comparison Between Early Glottic Carcinoma and Epithelial Dysplastic Lesions of the Vocal Fold Via Voice Analysis.

OBJECTIVE: Vocal fold leukoplakia is clinically defined by the presence of white mucosal lesions. Benign and malignant lesions of vocal fold leukoplakia can be distinguished clinically based on pathological biopsy. This study compared the acoustic and aerodynamic parameters of vocal cord carcinoma and dysplasia (mild to severe). MATERIALS AND METHODS: From February 2014 to December 2018, 1,925 voice evaluation assessments were collected before laryngeal microsurgery (LMS). Of 147 patients clinically diagnosed with vocal cord leukoplakia before LMS, 112 male patients were selected for examination. The pathologic findings after LMS were divided into the carcinoma group (56 patients) and dysplasia group (56 patients). Only patients with carcinoma in situ and early glottis cancer were included in the carcinoma group. Analysis of covariance was used to calibrate the age between the two groups. RESULTS: There was no difference in smoking duration between the two groups. F0 (P < 0.00), jitter (P < 0.00), and mean pitch (P = 0.010) were significantly higher, while the mean sound pressure level parameter (P = 0.024) was significantly lower, in the carcinoma group than in the noncarcinoma group. CONCLUSIONS: In patients with early glottis cancer, differences in voice analysis parameters may be used to differentiate between early glottic carcinoma and noncarcinoma.

Relationship Between Pepsin Expression and Dysplasia Grade in Patients With Vocal Cord Leukoplakia.

OBJECTIVE: To measure pepsin expression in patients with vocal fold leukoplakia and elucidate its clinical significance. STUDY DESIGN: Retrospective analysis of pathologic archive specimens. SETTING: Affiliated university hospital. SUBJECTS AND METHODS: The study included 45 patients with vocal fold leukoplakia and 19 with vocal fold polyps who underwent surgical treatment between December 2013 and July 2016. Masses were detected on both vocal cords in 5 patients with vocal fold leukoplakia and in 1 patient with vocal fold polyps. Immunohistochemistry was used to assess pepsin expression. In addition, the relationship of pepsin expression level with clinical characteristics of vocal fold leukoplakia was assessed. RESULTS: The rate of pepsin expression was high in the polyp group (75%) and the leukoplakia group (68%); however, the difference between groups was not significant (P > .05). Pepsin expression significantly increased according to grade of dysplasia (mild, 57.1%; moderate, 88.9%; severe, 100.0%; P = .034). Similarly, the percentage of lesions that exhibited strongly positive pepsin expression increased with the grade of dysplasia (mild, 37.1%; moderate, 66.7%; severe, 100.0%; P = .005). The leukoplakia recurrence rate was higher in patients with positive pepsin expression than in patients with negative pepsin expression but without a significant difference (P > .05). CONCLUSION: Our study suggests that pepsin was associated with the grade of dysplasia of vocal cord leukoplakia. Further investigation with appropriate control groups and controlling for other risk factors, such as smoking or alcohol consumption, is needed.

Leukoplakia: An Invasive Cancer Hidden within the Vocal Folds. A Multivariate Analysis of Risk Factors.

INTRODUCTION: Discerning the preoperative nature of vocal fold leukoplakia (VFL) with a substantial degree of certainty is fundamental, seeing that the histological diagnosis of VFL includes a wide spectrum of pathology and there is no consensus on an appropriate treatment strategy or frequency of surveillance. The goal of our study was to establish a clear schedule of the diagnostics and decision-making in which the timing and necessity of surgical intervention are crucial to not miss this cancer hidden underneath the white plaque. MATERIAL AND METHODS: We define a schedule as a combination of procedures (white light and Narrow Band Imaging diagnostic tools), methods of evaluating the results (a combination of multiple image classifications in white light and Narrow Band Imaging), and taking into account patient-related risk factors, precise lesion location, and morphology. A total number of 259 patients with 296 vocal folds affected by leukoplakia were enrolled in the study. All patients were assessed for three classifications, in detail according to Ni 2019 and ELS 2015 for Narrow Band Imaging and according to Chen 2019 for white light. In 41 of the 296 folds (13.9%), the VFL specimens in the final histology revealed invasive cancer. We compared the results from the classifications to the final histology results. RESULTS: The results showed that the classifications and evaluations of the involvement of anterior commissure improve the clinical utility of these classifications and showed improved diagnostic performance. The AUC of this model was the highest (0.973) with the highest sensitivity, specificity, PPV, and NPV (90.2%, 89%, 56.9%, and 98.3%, respectively). CONCLUSION: The schedule that combines white light and Narrow Band Imaging, with a combination of the two classifications, improves the specificity and predictive value, especially of anterior commissure involvement.

Clinical Analysis of Benign Vocal Fold Lesions with Occult Sulcus Vocalis.

PURPOSE: To discuss the correlation between benign vocal fold lesions and sulcus vocalis. METHODS: Analysis of the surgical data of 457 patients with benign vocal fold lesions and occult sulcus vocalis and preoperative voice evaluation and postoperative follow-up data from collected patients. RESULTS: A total of 61.7% of the patients had bilateral sulcus vocalis. Of the patients with bilateral sulcus vocalis, 64.9% had bilateral benign vocal fold lesions, and 35.1% had unilateral vocal fold benign lesions. Of the patients with unilateral sulcus vocalis, 74.3% showed associated ipsilateral vocal fold benign lesions, and 22.3% showed associated contralateral vocal fold lesions. In the 739 sides affected by sulcus vocalis, 255 sides of sulcus vocalis type I were not treated. There were 11 cases with 13 sides affected by mucosal bridges. The satisfaction rate for sound improvement was 79.6% by half a year after the operation. CONCLUSION: The occurrence of benign vocal fold lesions may be related to occult sulcus vocalis. We should attach importance to the treatment of sulcus vocalis in the diagnosis and treatment of vocal fold diseases.

Vocal Fold Leukoplakia: Which of the Classifications of White Light and Narrow Band Imaging Most Accurately Predicts Laryngeal Cancer Transformation? Proposition for a Diagnostic Algorithm.

The management of Vocal Fold Leukoplakia (VFL) remains problematic. There is no consensus on the indications or the timing for surgery. The objective was to select the most accurate classification for predicting low- and high-risk VFL in White Light Imaging (WLI) and Narrow Band Imaging (NBI) and to establish a diagnostic algorithm with a timely referral for treatment. A total of 259 VFL patients were included in the study; 186 lesions were classified as low-grade and 110 as high-grade dysplasia. The results of WLI acc. to the two-tier and the three-tier Chen 2019 classifications and NBI classifications: ELS, Ni 2011, and Ni 2019 with different cut-off points were compared with the pathological examination (HP). In WLI, the greatest agreement was obtained between type 3 of the three-tier classification and high-grade dysplasia (accuracy, specificity, and PPV: 80.4%, 92.0%, and 81.5%, respectively). Assessing VFL periphery in NBI, cut-off point 5 (Ni 2011 type V) demonstrated a higher accuracy, specificity, and PPV than 4 (83.1%, 93.6%, 85.5% and 77.4%, 74.9%, and 65.4%, respectively). In NBI, we observed higher accuracy, sensitivity, and PPV (84.1%, 93.0%, 85.2% vs. 80.7%, 81.3% and 71.3%, respectively) for cut-off point 5 (Ni 2019 type V and VI) in comparison to the cut-off point 4 group (type IV, V, and VI) (80.7%, 81.3%, 71.3%, respectively), and a higher kappa value (0.68 vs. 0.58) was obtained. We have shown that both the plaque image and the microvascular pattern on the leukoplakia periphery are critical in the diagnosis of high-risk VFL. The most accurate predictor of VFL malignant transformation in WLI is type 3 according to the Chen 2019 classification, while in NBI type V and VI according to the Ni 2019 classification.

[Narrow-band imaging for overcoming the microvascular pattern hidden under the plaque of the vocal fold leukoplakia].

Objective:To explore the application of narrowband imaging (NBI) in overcoming the microvascular pattern hidden under the plaque of vocal fold leukoplakia. Method:According to the morphology of intraepithelial papillary capillary loops (IPCL) around the plaque of vocal cord leukoplakia under NBI endoscopy,89 patients with microvascular morphology covered by plaque were divided into different groups. Subepithelial cordectomy was performed in 20 cases of benign group, subligamental cordectomy was performed in 45 cases of suspected malignant group, and transmuscular cordectomy was performed in 24 cases of malignant group, respectively. The lesions of vocal fold were biopsied with suspension micro-laryngoscope, and pathological examinations were also observed. Result:Pathological diagnoses showed that there were 10 cases of squamous epithelial hyperplasia, 8 cases of mild dysplasia, 21 cases of moderate dysplasia, 41 cases of severe dysplasia and carcinoma in situ, and 9 cases of invasive cancer, respectively. Spearman's analysis showed that there was a stronge positive correlation between the microvascular pattern of peripheral regions surrounding the plaque by NBI endoscopy and malignant degree of pathological classification(r=0.725, P<0.01). Conclusion:NBI endoscopy can overcome the "umbrella effect" of vocal cord leukoplakia. The microvascular morphology of the mucosa around the leukoplakia has a good correlation with final pathological diagnoses, and NBI endoscopy is helpful to determine the biopsy depth of the vocal cord leukoplakia.