Safety of flexible endoscopic biopsy of the pharynx and larynx under topical anesthesia

Head and neck cancer is the fifth most common cancer in the world [1]. The estimated incidence of nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal (i.e., laryngopharyngeal) cancers worldwide was approximately 385,000 new cases in 2012 with over 230,000 estimated deaths [1]. In The Netherlands, approximately 1565 new cases of laryngopharyngeal cancer were diagnosed in 2015 [2].

The early diagnosis is crucial for improving the treatment results of laryngopharyngeal cancer [3]. It increases survival and the chance of preserving laryngeal function [4]. Diagnostic assessment aims at histological diagnosis, mapping, and staging of the tumor [3]. The initial work-up starts with a history, physical examination, and imaging [5]. However, a biopsy is essential for the histological diagnosis of laryngopharyngeal cancer [3]. Traditionally, the biopsy of laryngopharyngeal lesions is performed under general anesthesia. Technological advancements in the types of transnasal endoscopes, instrument miniaturization, and topical anesthetic techniques have led to a shift in laryngeal management from the operation room to an office-based setting [6‐8]. Since the introduction of fiberoptic laryngoscopy in the 1970s, lighting and imaging techniques have improved substantially [9]. During the last decade, fiberoptic endoscopy has gradually been replaced by distal chip endoscopy [10, 11]. In the latter, information from a chip in the distal tip of the endoscope is send to a video processor, which creates a digital image and enables high-resolution imaging. Furthermore, endoscopes can be equipped with a built in working channel for passage of a flexible biopsy forceps or a laser fiber [6, 8, 10]. This enables clinicians to perform surgical procedures under topical anesthesia in an office-based setting, such as laser surgery or flexible endoscopic biopsy (FEB).

Office-based laryngeal FEB is reported to be safe [6, 12‐14], feasible [6], cost-effective [12, 15], and easy to perform [13, 16]. The advantages are an awake patient who is sitting in an upright position and able to control laryngeal function during the procedure, which can result in adequate visualization of the designated lesion [10]. Furthermore, there is avoidance of general anesthesia with possible health benefits [14, 17]. Its costs are relatively low compared with examination and biopsy under general anesthesia [12, 15]. Most importantly, FEB can often be performed during the initial outpatient visit or follow-up visit, which results in reduced diagnostic delay [7, 18]. An additional advantage of digital endoscopic techniques is the possibility of recording images, enabling more detailed reporting in the patient’s electronic file and comparison of images during follow-up. The disadvantages of laryngeal FEB are the need for a cooperative patient (e.g., able to sit still, minimal gag reflex) [8] and the inability to perform deep biopsies of submucosal tumors [12].

Due to the relative novelty of this office-based procedure, few studies are available and complication rates have been assessed in small sample sizes [6, 7, 12‐14, 19]. Therefore, the aim of this study was to investigate the complications of transnasal FEB under topical anesthesia in patients with benign and malignant laryngopharyngeal lesions. This study provides a more detailed insight into the safety of the procedure. To assess safety, complications were evaluated using the Clavien–Dindo classification, which is an objective scoring system for classifying complications and is also reproducible [20]. To our knowledge, the investigated study population is the largest in the literature.

Two hundred and one transnasal FEB procedures in 187 patients were included with 561 obtained biopsies, resulting in an average of 2.8 biopsies per procedure. There were 14 double inclusions, of which 13 were due to suspected recurrent lesions and one patient had two separate tumors that required FEB.

Patient characteristics are shown in Table 1. The study population consisted mostly of men (78.6%) of older age (mean 66.8 years). Almost one-third of patients used anticoagulants (29.9%). The most common biopsy site was the larynx with 138 biopsies (68.7%). Definitive histology results were squamous cell carcinoma in over half of the cases (57.2%) and severe dysplasia or carcinoma in situ in over one-fifth of the cases (21.4%). One histology result showed a lymphoma. In 5 out of 201 procedures, it was impossible to obtain a biopsy specimen. In one patient, the flexible endoscope could not be passed through the nose due to the small nasal anatomy of the patient; in two patients, a complication occurred during biopsy and the procedure, therefore, had to be aborted (i.e., laryngeal bleeding and supraglottic edema); in two cases, the patient could not tolerate the procedure (e.g., excessive coughing or pharyngeal reflex). In 1 out of 201 FEB procedures, histological classification could not be determined by the pathologist because of superficial biopsy specimens.

In 201 FEB procedures that were performed in this study, four patients had complications. Complications were laryngospasm, anterior epistaxis, laryngeal bleeding, and supraglottic edema; using the Clavien–Dindo classification system, these complications could be defined as two grade I (laryngospasm and anterior epistaxis), one grade II (laryngeal bleeding), and one grade IIIb (supraglottic edema) complication, respectively. The laryngospasm was self-limiting, while the other complications required an intervention. All complications resolved without sequelae.

In the last decade, technological advancements have caused a shift in the evaluation of most laryngopharyngeal lesions from the operating room to an office-based setting [6, 8]. However, before a diagnostic method is implemented in clinical practice, several factors need to be considered [14]. First, the safety of office-based FEB for laryngopharyngeal lesions has to be determined. The current study showed that four complications occurred out of 201 FEB procedures, and each complication did not occur twice. Thus, the incidence was 0.5% for each complication. A few studies reported on the safety of FEB for laryngopharyngeal lesions, showing low complication rates [6, 7, 12‐14]. Cohen et al. reported three complications in 112 patients, including “a post-procedure aspiration in one patient (without serious consequences) and a self-limited epistaxis in two patients” [13]. Further description, for example, on the intervention or outcome of these complications, was not provided by the authors. Lippert et al. assessed the safety of FEB in 24 transoral and 76 transnasal procedures [14]. No complications were reported and no association was observed with procedure tolerance or biopsy approach. Three other articles, with patient numbers varying from 12 to 76 patients, reported no complications during FEB [6, 7, 12].

To our knowledge, this is currently the largest study cohort for FEB reported in the literature. Furthermore, complications were systematically identified and classified according to a validated protocol. The results of the current study are in line with those of previous studies regarding the complications of FEB for laryngopharyngeal lesions, and showed four complications in a total of 201 procedures. Grade I and II complications, anterior epistaxis and laryngeal bleeding, demanded intervention as well as the grade IIIb complication of supraglottic edema. The grade I complication of laryngospasm was self-limiting. It is important to note that all complications recovered without sequelae. The case of supraglottic edema resulted in a tracheostomy, which was reversed approximately 2 weeks later.

Contraindications are an important consideration in any surgical procedure. In this study, a patient with a compromised airway was considered an absolute contraindication, which is in agreement with the reported literature [7]. In retrospect, the fourth case may not have had a compromised airway during biopsy, but he did have a compromised airway, which required a tracheotomy, when he was admitted to the emergency department. In some studies, anticoagulant use was considered a relative contraindication; patients were advised to stop anticoagulation use, defer the procedure, or they were excluded from further analysis [6, 7, 14, 15]. In the current study, anticoagulant use was not considered a contraindication and it was reported in 29.9% of the patients who underwent FEB. One of four patients (25%) with a complication in this cohort used anticoagulants but did not develop bleeding. Although care should be taken in patients who use anticoagulants, we believe that this should not be a factor that prevents a FEB under topical anesthesia.

A limitation of this study was the retrospective study design. Furthermore, there was a possibility of selection bias, and some complications may have developed after the outpatient clinic visit, which might not be included in this study. In addition, the physician judged whether a patient could cooperate in FEB under topical anesthesia. This is a subjective measure and it, therefore, might differ between physicians. It is important to note that this would occur less often with more experience gained with the number of laryngeal FEB procedures performed and local anesthetic techniques.

In this study, FEB for laryngopharyngeal lesions showed low complication rates and we thus conclude that the performance of FEB under topical anesthesia is safe for the histological diagnosis of benign and malignant laryngopharyngeal lesions. These results can contribute to a wider understanding of the possible complications that can occur during FEB and help guide physicians when FEB is first performed in the outpatient clinic.