Flexible endoscopic phonosurgery for treatment of functional sequelae after laryngeal oncologic surgery: a narrative review| ACTA Otorhinolaryngologica Italica

Abstract

Flexible endoscopic phonosurgery (FEPS) is one of the most recent and constantly evolving operative techniques in the field of minimally invasive laryngeal surgery. Thanks in part to the possibility of using new technologies, such as digital endoscopes, laser fibres, and different laryngeal injection materials, its fields of application have rapidly expanded. This narrative review describes the current possible indications of FEPS ranging from injection laryngoplasties in cases of vocal cord paralysis or mass defect, to the correction of dysphagia after open partial horizontal laryngectomies. Use of microscissors, microforceps, and laser fibres also allows this technique to be applied for removal of superficial vocal cord lesions, avoiding general anaesthesia in an increasing number of patients.

Introduction

The introduction of lens and fibreoptic instruments into otolaryngologic clinical practice in the early 1990s revolutionised the way in which the nose, ear, pharynx, and larynx were evaluated. A further step forward was the development of flexible fibrescopes equipped with an operating channel through which surgical instruments and lasers could be introduced, making it possible to perform operations without the need for general anaesthesia. The latest development consists in the production of flexible endoscopes with a miniaturised camera at one end (distal chip camera), potentially coupled with an operating channel, which have drastically improved image quality.

The first flexible surgical approach to the larynx was described by Gonzalez and colleagues in 1995 ¹. The term Fibre Endoscopic PhonoSurgery (FEPS) was coined for surgery performed using these methods, where the term ”fibre” has recently been replaced by ”flexible” (Flexible Endoscopic PhonoSurgery, FEPS) precisely because of the possibility of using endoscopes without an optical fibre for image transfer, which is instead performed digitally.

FEPS in the aftermath of laryngeal oncologic surgery is frequently used to inject various materials. Injection laryngoplasty is a relatively simple technique that nonetheless requires rigorous planning with regard to the anatomical site(s) to be treated and choice of filling materials, based on the aims to be achieved ^2-5. From its initial application in unilateral vocal cord paralysis, the indications for laryngeal injection have subsequently expanded and proposals for its application after cordectomy to restore an adequate neocord volume have appeared in the literature ^6,7. On the other hand, after open partial horizontal laryngectomies (OPHL) laryngeal injections are suggested to increase the neoglottic competence and improve swallowing in patients who, even after a maximal logopaedic rehabilitation, still present significant aspiration risks ⁸. Another possible field of application of FEPS in such a clinical scenario or in the presence of neurological disorders is represented by the modification of the cricopharyngeal muscle tone by injecting botulinum toxin.

Indications for FEPS and different types of injectable materials

FEPS has progressively established itself as a first-line therapeutic attempt in patients with:

1. contraindications to general anaesthesia due to associated comorbidities (e.g. severe heart or lung diseases);
2. difficult or impossible oro-tracheal intubation with ensuing suboptimal laryngeal visualisation due to reduced mouth opening, thyromental distance less than 6 cm, Mallampati class III or IV, reduced neck movement, and body mass index > 35 kg/m².

The main advantage of this method is the possibility to operate with the patient awake and collaborating. This makes it possible to modify the location and quantity of injected material on the basis of intraoperative findings and check the results of the procedure step by step while the patient performs swallowing manoeuvres and phonatory tasks. Additional areas of anatomical defects may be filled by subsequent injections.

The first FEPS procedures were carried out in cases of laryngeal paralysis in the intermediate-abducted position in order to medialise the vocal cord and obtain better glottic closure ⁹. Subsequently, FEPS was extended to cases managed by other oncologic surgical procedures ⁸.

The filling material injected should be as long-lasting as possible, but there are no substances with these characteristics approved for use into the larynx. In clinical practice, it is therefore possible to resort to the use of centrifuged autologous fat ⁹, hyaluronic acid ⁵, and calcium hydroxyapatite ¹⁰, which are absorbable over long periods of time and whose use varies depending on the purpose of the injection.

These materials are introduced using dedicated endoscopic flexible needles connected to a high-pressure gun for the injection of high-density materials. The calibre of these needles can be 19-gauge (for autologous fat), 23-gauge (for autologous fat or hyaluronic acid), or 25-gauge for non-dense hyaluronic acid and other substances, such as botulinum toxin.

Autologous fat, being a tissue that comes from the body, has the advantage of not causing foreign body or allergic reactions. It also contains stem cells that promote tissue regeneration in the areas where it is implanted. It is taken from the subcutaneous periumbilical region using Coleman’s technique ^11,12 under local anaesthesia obtained by lidocaine infiltration. Liposuction is performed with a 14-gauge Chiba needle through the umbilical fold (without cuts) inserted into a Luer-Lock 10 cc syringe. Two syringes are centrifuged for 3 minutes at 3000 rpm. After centrifugation, the separated liquid (oil) is eliminated and the fat to be implanted is kept with its stem cells contained within the adipose stroma ^13,14.

The material is poured into a 3 cc high-pressure gun with sterile technique and paying attention in not putting the adipose tissue in contact with air, in order to minimise the resorption of the injected fat. Fat must be over-injected since the liquid component is reabsorbed in a short time causing decrease of the injected volume with the consequence of reducing the effectiveness of the augmentation ¹⁵. Considerable quantities of fat can be needed, especially in case of tongue base augmentation.

Hyaluronic acid is a polysaccharide and a universal component of the extracellular matrix. It is non-species-specific and does not elicit any humoral or cell-mediated immune response. Adverse reactions are extremely rare and include local hypersensitivity and inflammation. Because it is so safe to use, it has become one of the most widely applied materials for laryngeal injection.

Two types of hyaluronic acid exist: linear and cross-linked. The linear type is the natural form of hyaluronic acid in human tissues. It features quick resorption and can be of both high and low molecular weight. It must be injected on the surface of the vocal fold as it increases mucosal elasticity and pliability with improved mucosal wave. The cross-linked type of hyaluronic acid is formed of linear molecules linked together to form macromolecules, with greater size, molecular weight and density compared to the linear type. It features slow resorption and is therefore used as an augmentation tool. It must be always injected deeply in the vocal muscle so as not to alter the mucosal wave.

Hyaluronic acid is a fluid substance that does not require high pressure for its injection. It reduces scar adhesions, favouring plane sliding, where areas of postoperative tissue stiffening have been created. To inject the material, a flexible needle of extremely small diameter (25-gauge) can be used, very useful for treatment of vocal scars with poor submucosal elastic tissue. Compared to other materials, however, hyaluronic acid has a lower filling effect and tendency to reabsorb faster.

Calcium hydroxyapatite (CaHA) is a reabsorbing long-lasting augmentation substance with good filling characteristics. Due to its viscosity, it requires a special preparation to be injected through the fibrescope: the needle (19-gauge) must be pre-filled with fluid hyaluronic acid to avoid blockage of the material during injection. This expedient facilitates the progression of CaHA, pushed by the high-pressure gun, through the thin flexible needles. Newly synthesised collagen forms around the injected CaHA particles. Over time, these are degraded by the body through normal metabolic processes, and can persist at the injection site for up to 12-18 months.

There is no evidence of granuloma formation following CaHA injection. However, this substance is generally reserved for cases where autologous fat is not available. For its use in FEPS, it must be diluted with non-cross-linked (linear) hyaluronic acid.

Despite the temporary duration of the injected substances applied through FEPS, the effectiveness of such a treatment is frequently long-lasting. In case of hyaluronic acid, the fluid material is reabsorbed, but the mechanical detachment of the mucosa from the underlying vocal ligament, which is kept in continuous movement during phonation and swallowing, persists over time.

As far as CaHa is concerned, its mass effect slowly reduces over time, thus allowing the patient to progressively adapt to the new anatomical conditions while maintaining adequate functional compensation.

Even the centrifuged autologous fat in the first months presents a partial resorption, but a share of material, especially if implanted in a richly vascularised anatomical site, remains vital and becomes a stable implant over time ^13-15.

Description of FEPS technique

Some simple procedures such as the injection of hyaluronic acid and drugs (cortisone, botulinum toxin...) can be conducted even in the absence of any anaesthesiologic support. In contrast, cooperation with an experienced anaesthesiologist is fundamental in more complex cases when the right amount of sedation, maintaining the patient awake and collaborating, is strongly warranted. In any case, monitoring cardiac function and having a venous access ready in case of need are certainly useful.

An intravenous infusion of 1-2 mg of midazolam is usually administered, resulting in conscious sedation, as is also the case in other endoscopic diagnostic procedures such as gastroscopy and colonoscopy.

Surgery can be conducted by 1 or 2 surgeons. In the first case, it is the same operator who holds the flexible endoscope with one hand, while with the other he/she introduces and manoeuvres various instruments. In the second case, one surgeon holds and directs the fibrescope while the other introduces and uses the instruments.

The patient is placed in a semi-sitting position in front of the operator and contact local anaesthesia with lidocaine nebulisation (e.g., 2% and then 10% solutions) in the nasal cavities, pharynx, and larynx is applied. Subsequently, a selective block of the internal branch of the superior laryngeal nerve can be obtained by infiltrating lidocaine into the aryepiglottic fold.

The tip of the flexible endoscope is then brought close to the point to be treated and through the operating channel the instruments needed (infusion needles, microforceps, microscissors, and laser fibres) are progressively inserted up to their visualisation within the endoscopic field (Fig. 1).

Injection laryngoplasty after cordectomy

Cordectomies were classified by the European Laryngological Society in 2000 with a subsequent revision in 2007 ^16,17. Currently, 9 types of cordectomy are recognised:

1. Type I or subepithelial cordectomy, i.e. resection of the vocal fold epithelium passing through the superficial layer of the lamina propria;
2. Type II or subligamental cordectomy, i.e. resection of the epithelium, Reinke’s space, and vocal ligament;
3. Type III or transmuscular cordectomy, i.e. resection up to the medial half of the vocal muscle;
4. Type IV or total cordectomy, i.e. resection of the entire vocal cord from the vocal process to the midline of the anterior commissure, reaching in depth the internal perichondrium of the thyroid ala;
5. Type Va or extended cordectomy encompassing the contralateral vocal fold and anterior commissure on both sides;
6. Type Vb or extended cordectomy including part of one arytenoid (more than the simple vocal process);
7. Type Vc or extended cordectomy encompassing the subglottis;
8. Type Vd or extended cordectomy including part of the supraglottis (false vocal fold, ventricle, supraglottic arytenoid, aryepiglottic fold);
9. Type VI or extended cordectomy including the anterior commissure, anterior thirds of both vocal cords, false vocal cords, petiole of the epiglottis, and anterior subcommissural area.

After type I cordectomy it is possible to inject linear hyaluronic acid to increase elasticity and improve the mucosal wave.

After type III (and sometimes type II) cordectomy, FEPS allows to perform an injection laryngoplasty with centrifuged autologous fat for augmentation of the partially resected vocal cord.

In case of autologous fat injection, this material must be injected deep into the vocal muscle or paraglottic space. In contrast, the fast-resorption hyaluronic acid is infiltrated superficially into the Reinke’s space.

In most extended cordectomies, injection is usually not possible due to the lack of an adequate quantity of residual tissue and, in case of autologous fat, absence of vascularisation which would prevent its integration with the surrounding tissues.

Injection laryngoplasty after OPHL

In recent decades, oncologic laryngeal surgery has undergone profound changes thanks, in part, to the introduction and development of lasers and robotic instrumentation, partly as a result of the evolution and popularisation of OPHL techniques, including supratracheal laryngectomies ¹⁸. On one hand, the extension of indications of transoral laser microsurgery has progressively supplanted vertical partial laryngectomies, while on the other supratracheal laryngeal surgery has made it possible to extend the classic indications of OPHLs to more advanced stages of disease. Moreover, the possibility of salvage surgery after failure of (chemo-)radiation by OPHL has been described and finds consensus in the literature ¹⁹. By increasing the range of possibilities of treatment of laryngeal cancer by OPHLs, the need to develop surgical techniques that are capable of remedying cases of functional failure has also arisen, in particular with regards to swallowing and breathing problems ^20-23.

Swallowing difficulties may occur after transoral laser or robotic surgery (in particular extended cordectomies) as well as after OPHLs type I, II, and III ²⁴. The causes of functional failure in these operations are mainly attributable to three factors:

1. impairment of sensitivity of the neopharynx and residual larynx, with consequent alteration of the reflex arch that triggers swallowing;
2. reduced motility of the residual larynx, with particular regard to the cricoarytenoid unit in OPHLs type II and III;
3. presence of structural anatomical defects causing the “slipping” and aspiration of the bolus.

The first two factors are mainly related to OPHL outcomes, while the third may also occur after transoral laser or robotic glottic and/or supraglottic resections. In fact, removal of large portions of the glottic and/or supraglottic regions can profoundly modify the anatomy of these structures, which are crucial for airway protection. After transoral procedures, in fact, removal of supraglottic/glottic structures is not followed by the pexy (as happens after OPHL) and therefore an important vertical gap is created between the tongue base and the glottal plane, generating an anatomical conformation favouring the slide of bolus within the respiratory tract during the intra-deglutition phase.

Another element potentially complicating postoperative swallowing recovery in case of advanced staged disease is represented by the possible need to deliver adjuvant radiotherapy. Although radiation can nowadays be performed with adequate sparing of delicate laryngeal tissues, this still generates xerostomia, reduced neolaryngeal sensitivity, motility and tissue elasticity of variable degrees, all elements that negatively affect swallowing. Not infrequently, therefore, patients who achieved good early postoperative functional compensation, may worsen and complain of dysphagia following adjuvant treatments.

As already stated, functional surgery for dysphagia is indicated only when maximal speech therapy rehabilitation failed to obtain satisfactory results.

Swallowing problems after OPHL

Functional problems after OPHL normally regress with time, but in some patients they may persist despite maximal efforts in terms of speech therapy. Dysphagia is undoubtedly the most important complication since its consequences may be sometimes dramatic (malnutrition, cachexia, recurrent ab ingestis pneumonia) and thus lead to drastic measures such as placement of gastrostomy or total laryngectomy for functional reasons. In other cases, minor but persistent swallowing disorders may remain (such as need of facilitating postures to swallow, sudden coughing fits, need for repeated clearing to eliminate residual food or secretion from neolaryngeal recesses), thus reducing quality of life by, for example, limiting patient’s participation to convivial occasions.

Causes of difficulties in swallowing recovery after OPHL can be traced to various factors. Some of these are related to surgical technique issues such as:

1. extent of resection;
2. dehiscence of the pexy or malalignment of the hyoid, epiglottis, and cricoid;
3. sensitive and/or motor nerves lesions with ensuing piriform sinus hypoaesthesia and/or arytenoid hypomobility/fixation.
4. other possible causes, however, may be related to more general conditions such as:
   1. superimposition or aggravation of systemic diseases;
   2. lack of patient collaboration and motivation (sometimes in association with reactive depression);
   3. unfavourable neck and/or neolaryngeal cicatricial outcomes.

The latter can lead to inadequate functioning of the cricoarytenoid unit or formation of false paths during the pharyngeal phase of swallowing, with bolus penetrating into the airways. In fact, food stagnation close to the neoglottis, where the food accumulates during swallowing, may be responsible for its passage into the airways during the inspiratory act that follows intra-deglutition apnoea.

The fibreoptic endoscopic study of swallowing (FEES) is the basis for planning rehabilitation surgery ^25,26. This investigation is performed using food of various consistencies and allows analysis of the pharyngeal phase of swallowing by identifying the path of bolus at the level of the reconstructed pharyngo-laryngeal pathway, quantifying the extent of penetration/aspiration and its locations. In patients with a still patent tracheostoma, the examination can be completed by performing trans-tracheostomy laryngeal fibreoptic endoscopy ²⁷ which allows evaluation of glottic or neoglottic closure during phonation ”from below” and extent of any intra-deglutition aspiration, thus overcoming the problem of swallowing ”white out”, which represents one of the major limitations of trans-nasal FEES. The endoscopic study in this case is performed to plan the subsequent rehabilitative treatment. Highlighting the critical areas where bolus enters the airway during different phases of swallowing is, in fact, the first step to correctly plan its surgical correction.

Transnasal injection laryngoplasty technique in fibreoptic endoscopy

In case of pexy dehiscence and/or posterior slippage of the cricoid with respect to the hyoid bone, it is useful to perform a CT scan, possibly with three-dimensional reconstruction. Before planning an invasive procedure such as the external revision of the pexy, it is still possible to attempt to correct such a problem by injecting inert material into the supraneoglottic region ²⁰.

The injection sites are planned after careful preoperative FEES and clearly vary depending on the residual laryngeal elements and areas where the greater gap during swallowing have been detected. Generally, preferential areas in which to inject the material are the following:

1. residual arytenoid(s);
2. residual mucosal flap covering the crico-arytenoid joint of a removed arytenoid;
3. upper edge of the cricoid ring in the anterior and/or lateral regions;
4. base of the tongue.

For injection into the arytenoid(s) and residual mucosal flap after its removal, the most suitable material is cross-linked hyaluronic acid, injected under the mucosa of the anterior region to improve neoglottic closure and mucosal wave during phonatory vibration.

Injection of autologous fat is also indicated for filling of the tongue base, where good vascular supply guarantees its proper integration. Furthermore, at the level of the tongue base, large tissue gaps can occur with excessive distance between the tongue and mobile part of the posterior neolarynx (e.g., residual arytenoid after OPHL type IIb) and a large amount of material is therefore required. In this case, autologous fat is an excellent and inexpensive source of filling.

Injection into the base of tongue is indicated not only after OPHL types IIb or IIIb, in which the epiglottis has been sacrificed, but may also be functionally useful in cases of OPHL type IIa and IIIa in which suprahyoid epiglottis is typically spared. The purpose of the injection at this level is to retro-place the residual epiglottis and thus reduce the anterior-posterior gap between this structure and the arytenoid(s).

Another important injection site is represented by the lateral portion of the neoglottis, in which case the injection is intended to fill the lateral defect that is sometimes present either on the side of the removed arytenoid or on that of the residual arytenoid, when the latter tilts without making any anterior sliding movement (Fig. 2).

Cricopharyngeal muscle spasm

The cricopharyngeal muscle contributes to formation of a sphincter separating the hypopharynx from the cervical oesophagus. It has the function of preventing air from entering the oesophagus when negative intrathoracic pressure is created during breathing, helping to prevent reflux of oesophageal and gastric contents into the pharynx. This muscle represents the main component of the upper oesophageal sphincter and cricopharyngeal myotomy is one of the universally codified and recognised treatments for dysphagia in cases of hypertonia of this muscle.

Treatment of cricopharyngeal muscular spasm may imply different approaches: external myotomy or rigid endoscopic myotomy ²¹, and minimally invasive treatment by injection of botulinum toxin ⁴.

In reviewing the literature, botox injection to treat cricopharyngeal dysfunction was first reported by Schneider et al. in 1994 ²⁸. The rationale for injecting the toxin at this level is to decrease the muscle tone and thus allow easier relaxation of the upper oesophageal sphincter. In case of external (percutaneous) treatment, electromyographic (EMG) monitoring is indispensable for the correct localisation of the muscle.

Endoscopic treatment can be performed under general anaesthesia with laryngeal suspension or by flexible techniques under local anaesthesia.

The advantage of FEPS technique is the possibility of performing botulin toxin injection in an outpatient setting under local anaesthesia and, above all, of locating the cricopharyngeal muscle under direct vision, without having to resort to EMG. Furthermore, fibreoptic endoscopy allows visual control of the precise positioning of the needle inside the muscle during the different phases of the procedure. Treatment usually involves the administration of 20-25 IU of botulinum toxin type A. It is necessary to wait at least 48-72 hours after injection before obtaining an appreciable functional result.

Duration of the treatment effectiveness is variable; generally, it is possible to recognise the first signs of further cricopharyngeal hypertonia within several months after botulin injection.

Laryngeal airway opening with the aid of fibre lasers

Sometimes, in the aftermath of partial laryngeal surgery, stenosis of the neolarynx may result in dyspnoea of varying degrees. Different techniques for airway restoration by transoral laser surgery under general anaesthesia have been widely described ²².

In certain cases of mild to moderate stenosis, however, minimally invasive treatments can be performed by FEPS technique under local anaesthesia. In particular, use of KTP fibre laser allows inducing ischaemia of granulomatous lesions abutting into the neolaryngeal lumen. KTP, in fact, is an “angiolytic” laser and is therefore particularly useful for treatment of richly vascularised neoformations such as “reparative” laryngeal granulomas, the formation of which may follow these types of open partial laryngeal procedures. Surgical technique involves inserting the laser fibre into the operating channel of the fiberscope and, after adequate contact anaesthesia, reaching the lesion and, in non-contact mode, staying few millimetres away from the target, applying the laser. During such a procedure, the lesion does not instantaneously decrease in volume, but rather becomes ischaemic, until it takes on a white colour similar to fibrous tissue. During the entire procedure, attention should be paid to not come into direct contact with the mucosal surface of the granuloma by the laser fibre, in order to avoid tissue carbonisation. In this regard, it is worth remembering that a KTP laser emits pulsed light, which is set by adjusting the energy delivered for each individual flash, its duration, and the interval between one pulse and another, which allows the tissue to cool down, thus enabling an effective in-depth treatment of the lesion while respecting its mucosal cover. Avoiding carbonisation allows not only faster healing, but also reduces the risk of recurrence, since de-epithelialised areas and thermal damage are limited. In the weeks following treatment, granulomas usually decrease in volume and complete regression after 15-20 days, depending on the initial size of the lesion, is generally observed.

Application of laser is usually associated with infiltration of triamcinolone (a long half-life corticosteroid) at the base of the neoformation itself, always by a fibreoptic endoscopic technique using flexible 25-gauge needles.

If the scar tissue obstructing the neoglottis is poorly vascularised, KTP laser will be scarcely effective, and other fibre lasers are therefore used, in particular the recently introduced fibreguided CO₂ or diode laser. The flexible fibreoptic CO₂ laser ensures easy, char-free tissue incision and coagulation of small vessels. This surgical technique is similar to that described for KTP, since it is applied without contact between the tip of the laser fibre and the target tissue, whereas the diode laser is a contact laser.

Conclusions

In recent years, FEPS has attracted a growing interest and diffusion in the ENT specialist field, and to date can be considered one of the phonosurgical treatment techniques that complements microlaryngoscopy and thyroplasty. The strengths of this technique are the possibility to treat patients under local anaesthesia and those with difficulties to transoral exposure, but most importantly to intraoperatively monitor the efficacy of the treatment. The latter characteristic allows the surgeon to intraoperatively modify the surgical planning, a feature of considerable importance since these are generally interventions with a rehabilitative purpose of voice or swallowing.

Conflict of interest statement

The authors declare no conflict of interest.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

All authors of this study made significant contribution to the drafting of the manuscript, and have read and approved the current version of submitted manuscript.

Ethical consideration

Not applicable.

Figures and tables

Figure 1.Instruments used for FEPS injection: 1) short operative flexible fiberscope (23 cm); 2) high pressure pistol; 3) polycarbonate syringe; 4) flexible surgical forceps; 5) injection needle catheter; 6) lidocaine; 7) hyaluronic acid.

Figure 2.Injection points in the neoglottis and indicated materials: 1) arytenoid (hyaluronic acid); 2) residual mucosal flaps upon removal of one arytenoid (hyaluronic acid, Radiesse, PolyDiMethylSiloxane [PDMS]); 3) anterior part of the cricoid cartilage (PDMS, Radiesse); 4) lateral part of the cricoid cartilage (PDMS, Radiesse); 5) base of tongue (autologous fat, PDMS, Radiesse).

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