Despite the progress made in the diagnosis and treatment of the UADT SCC, the advanced stages of disease frequently encountered at the first clinical consultation, and the not negligible rates of local-regional persistence/ recurrence and distant metastases still have a negative impact on patient survival 17
. In addition, according to the "field cancerization" phenomenon, multiple SCC frequently occur within the UADT, either synchronously or metachronously, resulting in a definite reduction in overall survival 18
Panendoscopy of the UADT offers a higher diagnostic rate of superficial synchronous lesions compared to either physical examination or routine radiological investigations 19
. However, the possibility of standard WL endoscopy detecting lesions, at an earlier stage, can be extremely difficult in some subsites of the UADT (e.g., OP and HP) even after many repeated manoeuvers of the endoscope by experienced physicians 7
. This problem becomes even more evident when considering the post-treatment scenario, particularly if iatrogenic and actinic changes contribute together in masquerading potential persistences/recurrences. In this perspective, NBI has been demonstrated to significantly improve the efficacy of screening, initial evaluation, and surveillance of head and neck cancer, even in areas traditionally considered "difficult" to adequately assess by means of endoscopy, or after organ preservation protocols 7 8 13-15
Muto et al. 7
were the first to recognize the potential advantages of NBI in otolaryngology. In particular, during endoscopic post-treatment surveillance of patients, previously treated for oesophageal cancer, using this instrumentation they were able to identify 34 metachronous lesions in OC, OP, and HP (only 5 of which were also evident by means of standard WL endoscopy). Since then, many groups, from independent institutions, have confirmed these encouraging findings in prospective series of patients 8 10-15
The main end-point of the present study was, therefore, to compare the diagnostic gain of NBI and HDTV in the different sites of the UADT, thus confirming, on a large series, the overall accuracy of these techniques already observed by our group 13-15
. For example, in the O-OP sites, NBI is always feasible in conjunction to HDTV, both in the pre- and post-treatment settings, even under local anaesthesia: this translates into a diagnostic gain of 25%, with early detection of synchronous and metachronous UADT tumours (9.3%), as well as of early persistences/ recurrences (7.2%). Moreover, in these anatomical sites, we observed the highest values of Se, Sp, PPV, NPV, and Ac, compared to other UADT sites.
Watanabe et al. 8 11
were the first to report that the use of NBI endoscopy in the assessment of laryngeal cancer leads to early detection of abnormal microvascular changes and is useful in distinguishing between low- and high-grade dysplasia (with Se and Sp rates of 91.3% and 91.6%, respectively). Our results confirm these data, since the application of NBI in the pre-operative setting allowed the detection of 52 lesions that were not visible at routine WL endoscopy. Nonetheless, in the L-HP sites, we observed that NBI reaches the highest diagnostic accuracy during intra-operative rigid endoscopy when coupled with a HDTV camera. In this setting, the rate of Se significantly improved from 69% (without HDTV) to 98%. The application of NBI and HDTV in the L-HP sites, with its diagnostic gain set at 21%, showed the greatest usefulness in the better definition of neoplastic superficial spreading, with consequent improvement in control of the peripheral narrow-margin obtained by trans-oral microsurgical resection of glottic and supra-glottic early tumours. Future improvements in technology, in terms of distal microchip miniaturization, should further improve the accuracy of NBI even under local anaesthesia, both in the pre- and post-treatment scenarios.
Although most Authors agree that NBI, with or without HDTV, seems to be a very promising diagnostic tool, the method certainly has some limitations. The most relevant is the possibility of generating, at least in the early phase of the learning curve, an increased number of false positives with consequently unnecessary biopsies. This fact is related primarily to acute or chronic inflammation as well as to post-actinic changes. However, Nonaka et al. 9
found that although intraepithelial papillary capillary loops can be modified by inflammation, it is generally possible to distinguish them from those observed in neoplastic lesions on the basis of their ill-defined margins and relatively low density. Recently, Lin and Wang 20
showed that even though post-actinic mucosal fibrosis, nasopharyngitis, and osteoradionecrosis can mimic recurrences during endoscopic follow-up of nasopharyngeal SCC patients, treated by RT, NBI can reliably distinguish them from early recurrences compared to conventional WL endoscopy. In a previous study from our group, we found that NBI allows a 20% higher detection rate of persistences/recurrences in patients affected by UADT SCC and previously treated by RT and/or CHT-RT. The high specificity of NBI helped to significantly reduce the number of unjustified biopsies. Moreover, our results showed that there is no statistically significant difference between the NBI false positive rate after RT or CHT-RT compared to that of a cohort of untreated patients 15
. In contrast, we found that the major factor influencing the rate of false positives, at NBI, was related to our learning curve, being highest in the first 6 months of use and negligible in the last 6 months.
The second potential drawback of NBI concerns the estimation of its genuine Sp. In fact, it would be both nonethical and unfeasible to perform random biopsies in every patient with negative WL and NBI examinations. In order to overcome this limit, we judged as true negatives only those patients who underwent more than one endoscopic NBI evaluation during their follow-up and were found to be persistently negative.
In conclusion, although further technological advancements, such as the possibility to incorporate HDTV in a flexible trans-nasal videoendoscope are needed in order to optimize the diagnostic gain of NBI in the L-HP sites, its overall Sp, as well as NPV and Ac, allows us to consider this endoscopic tool as an essential aid in diagnosis, treatment, and post-therapeutic surveillance of UADT SCC.