Objectives/Hypothesis: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus 6 and 11. The characteristic feature of this disease are wart-like lesions covering the respiratory epithelium with a predilection for the larynx. There is no curative treatment for the disease. The goal of the treatment is a total surgical removal of the papillomatous lesions in order to reduce the number of relapses. Therefore, a good visualization method of papillomas is crucial during surgery. The aim of the study was to compare the accuracy of narrow band imaging (NBI) to the use of white light alone in detecting RRP. Methods: The study was carried out between April 2013 and November 2015 at Poznan University of Medical Sciences, Department of Otolaryngology, Poland. Rigid endoscopy with conventional white light (WL) and NBI (CV-260SL processor and CLV- 260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan) was performed in all patients during direct laryngoscopy. All anatomical sites of the larynx and trachea were assessed using the Dikkers scale and Derkay total site scoring system with WL and NBI. The consensus was reached as to the number of lesions seen in WL compared to NBI. Results: During 36 microlaryngoscopies, the number of papillomas detected in the larynx (by Derkay total site score) differed significantly between white light endoscopy and NBI (Wilcoxon test p = 0.000655). In endoscopy with NBI, a mean of 1.3 more papillomas in Derkay total site score was detected in comparison to white light endoscopy NBI showed additional areas of diseased tissue in 15/36 (41.67%) patients. Conclusions: NBI as an additional tool during microlaryngoscopy can improve the detection of papillomatous lesions.
Keywords: Research Article; Medicine and health sciences; Diagnostic medicine; Signs and symptoms; Lesions; Pathology and laboratory medicine; Oncology; Cancers and neoplasms; Papillomas; Surgical and invasive medical procedures; Endoscopy; Physical sciences; Physics; Electromagnetic radiation; Light; Visible light; White light; Biology and life sciences; Anatomy; Neck; Throat; Larynx; Otolaryngological procedures; Cancer treatment; Surgical oncology; Clinical medicine; Clinical oncology
Recurrent respiratory papillomatosis (RRP) is a rare (with an incidence of 4.3 per 100 000 among children and 1.8 per 100 000 among adults [[
The current treatment protocols for RRP include surgery, aiming removal of epithelial lesions while maintaining the underlying anatomical structure of the vocal folds [[
Therefore, we examined the usefulness of narrow band imaging (NBI) in the intraoperative assessment of patients suffering from RRP, analyzed whether this method could help to identify additional RRP lesions during surgery and compared the positive predictive value of NBI vs. white light alone in detecting RRP.
Narrow band imaging (NBI) is a novel optical technique that selects the wavelengths of white light with two peaks around 415 and 540 nm. These wavelengths penetrate only into the superficial layer of mucosa and are absorbed by haemoglobin in capillary vessels. The technology allows identification of vascular patterns that are invisible during white light endoscopy and facilitates identification of superficial capillaries and neoangiogenesis in the abnormal mucosa. The most widely used classification to describe pre- and cancerous lesions of mucosa in NBI examination was presented by Ni et al. [[
The prospective study was carried out between April 2013 and November 2015 in a tertiary referral hospital at Poznan University of Medical Sciences, Department of Otolaryngology, Poland. The study included patients with suspected papilloma-like lesions and those who had a laryngeal papillomatosis confirmed in histology before. All patients underwent routine microlaryngoscopy under general anaesthesia. There were no exclusion criteria.
Thirty-six (
Informed consent: Informed written consent was obtained from all individual participants included in the study.
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was approved by Bioethics Committee of Poznan University of Medical Sciences.
The Wilcoxon test was conducted to compare the results obtained with WL and NBI. The chi-squared test was used to test the difference in number of papillomas according to the Derkey total site scoring system with NBI versus WL. Correlation between age, number of procedures and Derkay total site score in endoscopy with WL and NBI was analyzed using the Kruskal-Wallis test. All tests were conducted at the significance level of 0.05. All of the analyses were performed using Statistica version 12.0 (StatSoft Polska) and Excel 2007 (Microsoft Corp.).
The Derkay total site score of papillomas detected in the larynx differed significantly between endoscopy with WL and NBI (Wilcoxon test, p = 0.000655). In endoscopy with NBI, a 1.3 point increase in Derkay total site score was detected compared to WL endoscopy (Table 1), Figs 5 and 6. All lesions were histologically assessed and confirmed by a dedicated pathologist from the Department of Pathology at Poznan University of Medical Sciences. NBI showed additional areas of diseased tissue in 15/36 (41.67%) patients. The number of additional samples in all patients was 26 (laryngeal ventricle: 5/26 (19.24%), false vocal fold: 10/26 (38.46%), true vocal fold: 3/26 (11.54%), arytenoid: 2/26 (7.69%), aryepiglottic: 2/26 (7.69%), subglottic: 1/26 (3.85%), trachea: 1/26 (3.85%), anterior commissure: 1/26 (3.85%), posterior commissure: 1/26 (3.85%).
Table 1: Characteristic of patients with confirmed RRP treated by CO2 laser.
patient ID № of previous procedures Dikkers score WL endoscopy (Derkay total site score) NBI(Derkay total site score) Exact location of additional lesions detected by NBI 1. 54 3 10 14 Subglottic + trachea 2. 24 1 2 4 True vocal folds 3. 4 3 4 4 - 4. 1 2 2 2 - 5. 3 3 4 8 False vocal folds 6. 1 1 4 8 Laryngeal ventricle, Anterior commisure 7. 8 1 4 4 - 8. 1 2 2 2 - 9. 15 1 6 10 Laryngeal ventricle 10. 3 3 4 4 - 11. 8 3 2 6 False vocal folds 12. 119 1 6 12 Aryepiglottic, false vocal folds 13. 15 3 10 10 14. 10 3 4 4 15. 2 3 4 4 16. 9 1 4 4 - 17. 4 1 4 6 False vocal fold 18. 5 1 4 8 AryepiglotticFalse vocal fold 19. 30 3 6 6 20. 1 1 4 6 Arytenoid 21. 20 3 4 4 - 22. 2 3 10 10 23. 3 1 8 10 True vocal fold 24. 7 3 10 14 Arytenoid, false vocal folds 25. 106 3 10 10 - 26. 0 2 2 2 - 27. 1 2 2 2 - 28. 2 2 2 2 - 29. 48 2 2 2 - 30. 40 3 4 4 - 31. 1 2 4 4 - 32. 3 1 2 4 Posterior commisure 33. 1 2 2 2 - 34. 0 1 6 8 Laryngeal ventricle 35. 90 1 4 6 Laryngeal ventricle 36. 1 1 2 2 - Total site score - - 164 212 -
There was a statistically significant correlation between the Dikkers score and additional lesions detected with NBI (Chi2, p = 0.00069). Additional papillomas were visualized in NBI in 11/14 (78.57%) patients with sessile lesions (unifocal or multifocal) scoring 1 on the Dikkers scale. No additional papillomas were detected in NBI among patients with exophytic papillomas scoring 2 on the Dikkers scale, however in 4/14 (28.57%) patients with exophytic papillomas scoring 3 on the Dikkers scale there were additional lesions found in NBI.
There was no significant correlation between age, number of procedures and Derkay total site score in endoscopy with white light and NBI (Kruskal-Wallis test, p >0.05).
There was also no statistically significant correlation between age and assessment of lesions using the Dikkers scale (Kruskal-Wallis test, p = 0.9600).
The analysis confirmed that there is no statistically significant correlation between gender and assessment of lesions using the Dikkers scale (Chi2, p = 0.28680). Recurrence of papillomas was observed in 1/36 patients within 12 months after the operation.
In the presented paper, we focused on the intraoperative use of narrow-band imaging (NBI) in patients suffering from RRP. NBI has been characterized by high sensitivity, specificity, negative predictive value and positive predictive value in the detection of precancerous and cancerous lesions of head and neck region in several studies [[
The first study showing increased sensitivity of NBI in the detection of RRP lesions compared with conventional WL alone was presented by Tjon Pian et al. [[
Ochsner and Klein reported the use of NBI in the treatment of laryngeal papillomatosis in awake patients. They concluded that NBI improved the ability to visualize diseased tissue in 90.0% of patients and showed additional areas of diseased tissue in 46.7%. The most interesting observation was the role of NBI in determining the borderline between papillomas and healthy tissue. NBI defined the borders of disease more clearly in as much as 76.7% of all patients [[
According to our results, NBI endoscopy was highly useful in visualizing superficial papillomas as well as lesions located in the false vocal folds and laryngeal ventricle. Although we consider NBI to be easy to use (one button to switch between WL and NBI), we have also realized that NBI has some limitations. First of all, the learning curve for recognizing and differentiating lesions is a long-lasting process. The longer the method is used to visualize epithelial vessels, the easier it is to recognize the characteristic pattern of vessels corresponding to papillomas [[
In our opinion, the most important aspect of treatment of RRP is visualizing even very small laryngeal papillomas for complete surgical removal. Using NBI as an additional tool during endoscopy improved the detection of these lesions in the current study.
DIAGRAM: Fig 1: Laryngeal papillomatosis in white light (WL).
DIAGRAM: Fig 2: Laryngeal papillomatosis in NBI.
DIAGRAM: Fig 3: Laryngeal papillomatosis in white light (WL).
DIAGRAM: Fig 4: Laryngeal papillomatosis in NBI with vessels along the central axis of each papilla.
DIAGRAM: Fig 5: Laryngeal papillomatosis invisible in white light (WL).
DIAGRAM: Fig 6: Laryngeal papillomatosis visible in narrow-band imaging (NBI).
By J. Jackowska, Writing – original draft; H. Klimza, Writing – original draft; P. Winiarski, Writing – review & editing; K. Piersiala, Writing – review & editing and M. Wierzbicka, Supervision