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papillary capillary loops (IPCL) are well demonstrated by NBI and may correlate with depth of invasion of super ficial mucosal carcinoma. 7,8 Gradually, NBI became a valuable tool in the early detection of esophageal 3,4 and colon 5,6 cancer. NBI has only recently been introduced to laryngeal endoscopy, and has gained popularity in the identification and follow-up of papillomatosis 9,10 as well as malignant and premalignant lesions. 11–22 Early studies investigating the use of NBI in the larynx emerged at the beginning of the present decade. 11–14 The latter studies were mostly descriptive, trying to define the characteristics that differ entiate malignant from benign laryngeal lesions. In 2011, Ni et al. applied IPCL classification to 104 suspected pre cancerous or cancerous laryngeal lesions. The authors concluded that the IPCL classification using NBI was closely associated with the histological findings; whereas type I to IV lesions were considered nonmalignant, type V lesions correlated with malignancy. IPCL types Vb and Vc, which represent irregular, tortuous, linelike IPCLs had higher sensitivity and specificity for invasive carcinoma. 11 The validation of laryngeal NBI is better established in the operating room (OR); Piazza et al. examined a series of patients with preoperative flexible NBI and showed 61% sensitivity and 87% specificity for detection of malignancy. However, intraoperative high-definition television (HDTV) NBI in the same patients resulted in higher rates of both sensitivity and specificity: 98% and 90%, respectively. 12 Consequently, the use of intraopera tive HDTV NBI was later suggested to reduce the inci dence of positive superficial surgical margins during transoral laser microsurgery (TLM). 15 The OR setting facilitates the use of HDTV with rigid close-up endoscopy, and therefore maximizes NBI’s benefits. Nevertheless, the additive value of NBI in the more challenging setting of an office examination in awake patients has not yet been confirmed. In our study, we aimed to investigate and further delineate the role of NBI preoperative assessment in the office and in the decision-making process with suspected lesions. The study attempts to evaluate differences in the estimation of lesions’ size and pathology using NBI, compared to white light (WL). MATERIALS AND METHODS This was an observational matched study that compared the interpretation of NBI and WL images of vocal fold (VF) lesions suspected of malignancy by otolaryngology specialists. The study was approved by the institutional ethics committee. Forty-five VF lesions from 36 patients were included in the study. All patients were examined with both WL and NBI imaging modalities using flexible endoscopy with an ENF-V2 digital video rhinolaryngoscope (Olympus Medical System Cor poration, Tokyo, Japan) in our referral center’s voice clinic between 2013 and 2015. The examination revealed unilateral or bilateral VF lesions suspected of malignancy. Exclusion criteria were: 1) patient was not examined by both WL and NBI; 2) WL or NBI images had a degraded quality; and 3) were unable to provide WL and NBI images that were similar in their quality, distance, and angle. All lesions included in the study were

biopsied; 21 were invasive carcinoma, 22 were mild or moderate dysplasia, and two lesions were benign. Two images, one WL and the other NBI, were selected for each lesion. The selected images demonstrated the lesion clearly along with specific anatomical landmarks such as the anterior commissure and the vocal process. Moreover, the two images were comparable regarding their quality and their distance and angle from the VF. All images were presented randomly and evaluated by six otolaryngology specialists (the observers). Each image was pre sented on a personal computer screen monitor using Power Point 2007 (Microsoft Corporation, Redmond, WA). Each slide contained one image of the lesion (WL or NBI) along with three tasks for the observers: 1) to draw the lesion’s margins with a pen on a schematic VF image, 2) to estimate the lesion’s size using a multiple choice answer, and 3) to estimate the lesion’s pathology by a multiple choice question. The analysis of the first task (drawing the lesion on the schematic image) was done using a dense grid system and manual measurements to calcu late the area of the drawn lesion and the distance of its margins from the vocal process and the anterior commissure. Assuming the length of the VF in the schematic image was 18 mm, each square of the grid system in the schematic image represented 0.46 3 0.46 mm 2 . Samples for completion of this task can be found in Figure 1. In the second task, the observers answered the following multiple choice question: “What is the lesion’s size: less than one-third of the VF area; between one-third and two-third; or over two-third?” To reach the answer, the observ ers were instructed to consider the traditional segmentation of the VF into thirds, assuming the anterior two-thirds are the membranous portion of the VF, and the posterior third is the cartilaginous portion. In the third task, the observers answered the following multiple choice question: “What is the lesion’s probable pathology diagnosis: nodule/cyst/polyp, papillomatosis, benign keratosis, dysplasia, invasive carcinoma, other, or unknown?” The observers were directed to avoid the answer “unknown” when possible. This question was also used to calcu late the sensitivity, specificity, and positive and negative predic tive values for detection of malignancy. The images were presented to the observers in three sepa rated sessions. The first session included a simulation of the questionnaire. The objective of this session was to familiarize the observers with NBI images and with the study’s methods. Data from this session were not included in the analysis. In the second session, the 45 lesions were presented to the observers randomly, either by WL or by NBI. In the third session, the 45 lesions were presented randomly again, this time by the alter nating imaging modality (if a lesion was presented by WL in the second session, it was presented by NBI in the third session and vice versa). Altogether, each of the six observers viewed 90 images of 45 lesions (one WL and one NBI) in two sessions; in each session only one image of each lesion was presented. The observers were not restricted in time to fulfill the tasks. Howev er, there was an essential recess of at least 30 minutes between each session. The results of the two imaging modalities were compared with each other and with the final pathology. To test the associ ation between two categorical variables, v 2 test was used. Paired t test was applied to test differences for quantitative var iables. All tests applied were two-tailed, and a probability value of 5% or less was considered statistically significant. Kappa coefficient was performed to assess agreement of categorical variables, and intraclass correlation coefficient (ICC) was used to calculate the agreement of quantitative variables. Statistical analyses were performed using SPSS Statistics version 20.0 (IBM, Armonk, NY).

Laryngoscope 127: April 2017

Shoffel-Havakuk et al.: NBI Preoperative Detection of Malignancy 895

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