MIDDLE-EAR CLEFT GAS DEFICIT DISEASE TO MIDDLE-EAR CLEFT ACQUIRED CHOLESTEATOMA: PATHOGENESIS-ORIENTED MANAGEMENT
Middle-ear cleft gas deficit disease / atelectasis
Definition
Middle-ear cleft atelectasis is an incomplete expansion of the middle-ear space associated with medial displacement of the eardrum towards the promontory. In most cases, the eardrum is atrophic. Middle-ear cleft atelectasis belongs to chronic otitis media. The clinical picture is a tympanic membrane retraction pocket which consists of an invagination of a weakened tympanic membrane into the tympanic cavity.1
The retraction pocket constitutes a distinct clinical entity, the importance of which is determined by three types of criteria: topographical, quantitative and qualitative. The topographical criterion means the location, in the pars flaccida, in the pars tensa, or in both. The quantitative criterion refers to the dimension – is it total, or partial; the depth – is the pocket deep or shallow; does the extent allow to control it under the operative microscope? The qualitative criterion refers to the behavior of the pocket – is the pocket self-cleaning or not; is there a bone erosion of the lenticular process of the incus and/or of the tympanic frame; is the pocket adherent to the middle-ear structures, or not?2
Pathogenesis
The pathogenesis of the middle-ear cleft atelectasis is pluri-causal.3 This is, in fact, no matter of inappropriate scientific curiosity, but rather the sharing of a conviction that there are at least five main causes to be carefully taken into account when therapeutic management of the pocket is undertaken.
The indisputable starting point is the presence of an inflammatory process of the upper-airways mucosa and, more particularly, of the middle-ear cleft mucosa. Once initiated, the process will pursue its natural course which will lead to the picture of a well-determined clinical entity. This is a continuous and as such a long dynamic process.4,5
A second cause is the negative pressure, the ‘gas deficit’, in the middle-ear cleft. How does gas deficit happen? The middle-ear cleft is lined by mucosa with an embedded vascular network, which provides the metabolic requirements of the mucosa and also represents a source and sink for trans-mucosal gas exchange between the middle-ear cleft and local mucosal blood.
Gas exchange depends on variations in the middle-ear cleft blood flow. In a similar fashion as alveoli in the lung, the direction of gas exchange is predicted by the differences in partial pressure of the component gases in the middle-ear cleft and in the blood compartment.
When the mucosa is healthy, there is an equal rate of gas exchange because oxygen and nitrogen are absorbed by the mucosa in the same rate as carbon dioxide is expelled. For a given mucosal blood flow, nitrogen is the rate limiting factor of the middle-ear cleft gas loss because it diffuses slower than carbon dioxide and oxygen that equilibrate relatively quickly with venous blood.6 Inflammatory processes increase both number and diameter of the blood vessels in the middle-ear cleft, increasing the blood flow and gas exchanges ac-cordingly.7 (Fig. 1).
Fig. 1. Gas exchanges between the middle-ear cleft and the blood compartment through healthy (a) and inflamed mucosa (b).
The more inflamed and vascular the mucosa, the greater the rate of gas absorption.
When a light gas deficit, or a small negative pressure, that are normally well compensated, increases into the middle-ear cleft to the extent that it becomes no more compensated, pathology occurs. This constitutes one of the causes of the tympanic membrane retraction pocket formation.
A third cause is the atrophy of the tympanic membrane lamina propria, atrophy of the mesenchymal layer.
General process: The atrophy of the lamina propria never occurs as a sudden or isolated process, but always implies a more or less long-standing involvement. This tissular atrophy is explained by two kinds of mechanisms: biophysical and biochemical.
The bio-physical explanation is based on the visco-elastic properties of the lamina propria.8 The tympanic membrane lamina propria is a network of load-bearing fibers embedded in a gelatinous matrix. The fibers are cross-linked. When subjected to constant stress, due to ‘negative pressure’ in the middle-ear cleft, the crosslinks gradually break down causing further extension of the material. The volume of soft biological tissue is believed to remain constant under the action of external forces. Therefore, when the tympanic membrane lamina propria is stretched, it will inevitably become thinner.9
Under inflammatory conditions, the tympanic membrane gets thicker both at sub-mucosal and sub-epithelial layers. This thickening could be responsible for an increase in constraint forces applied on the tympanic membrane and could lead to a degenerative process of the fibers of the lamina propria. When the atrophy has been installed, the tympanic membrane loses his mechanical armature and a retraction may occur even under the effect of moderate middle-ear cleft pressures.10
The bio-chemical explanation is based on the damage on the connective tissue, particularly, the rupture of the di-sulfure bridges, by collagenases, metallo-proteases and cytokines, liberated during the inflammatory process.
Concerning the local process: we know that, in adults, the morphologically weaker areas of the tympanic membrane are the pars flaccida and the postero -superior quadrant of the pars tensa.3
The more specific weakness of the pars flaccida is the notch of Rivinus that corresponds to the absence of the tympanic bone at the top of the tympanic frame. At that point, there is also no fibro-cartilaginous ring. Histologically, at this point, the structure of the lamina propria is not clearly organized and, upon dissection, we have even noted congenital defects in these fibrous layers, in 4% of normal adult temporal bones.
With regard to the weakness of the posterior part of the pars tensa, since its early development the posterior arm of the tympanic bone is the most delicate portion of this structure, and is thinner and shorter than the anterior arm. The circular fibers of the lamina propria are more delicate and are seldom seen in this area. The area is thinner (about 60 microns) than near the rim (about 90 microns). The strain must therefore be greater in the thinner parts.
A fourth cause considered is the tympanic membrane stratified squamous epithelium dysfunction. This epithelium is the site of two kinds of specific movement. The centrifugal keratin dispersion process involves the superficial layers, and is particularly well suited to cleaning of the external auditory canal.11 When disturbed, it provokes an accumulation of keratin into the pocket.
The centripetal epithelial migration process is conspicuous in some pathological cases such as, for example, the healing of tympanic membrane perforations.12
Centripetal movement involves the whole stratified squamous layer which lines the perforation.13 In this case, two conditions are required: the presence of free edges and the presence of a substratum able to give the cells a specific directional impulse. This is the ‘contact-guidance’ phenomenon, explained by Weiss.26 These two conditions do not exist when considering a retraction pocket.
An additional contributor is the concomitant association of the local morphological predisposing factors which act as a catalyst agent for the pathogenic mechanism of the tympanic membrane retraction pocket. These local morphological predisposing factors are the unlimited anatomical variants of the temporal bone and their consequences upon the physiology of the middle-ear cleft.14 They are the result of the dynamic of the organogenesis of the entire temporal bone. This organogenesis is a true ‘living puzzle’. Each piece has to develop individually, and at the same time, fuse with the other pieces which are also growing, immersed in unstable surroundings. No more than a minute delay or minuscule modification in the sequence of those programmed events and more or less severe modifications of the normal morphology will be seen. This could generate torsion and traction of the mucous folds of the middle-ear cleft, which would have an effect upon muco-ciliary clearance and pressure variations balance in the middle-ear cleft, associated with nerve and blood supply disturbances and subsequently interactions on the local metabolism.15 They are particularities or variants which are not considered to be anomalies or pathological phenomena because of the frequency of their occurrence. These variants are tiny morphological modifications, surgical observations, which may sometimes be correlated with certain functional or clinical events: 91% of the external auditory canals that we dissected at the time of tympanoplasty, in cases of chronic otitis media, show protruding lateral posterior bony cristae, as opposed to only 19 in 100 normal temporal bones. We can explain this fact by a slight rotational shifting of the tympanic ring during its early development. Moreover, the fusion of the two arms of the tympanic bone with the other components of the temporal bone takes place during a relatively long period of time and is not synchronous.16 The definite coupling, slow or rapid, is responsible for minute particularities in the normal morphological development. The concomitant association of local morphological predisposing factors with other causes initiates and triggers the other pathogenic causes, namely: inflammatory process of the upper air ways mucosa, middle-ear cleft ‘negative pressure’ and both tympanic membrane lamina propria atrophy and stratified squamous epithelium dysfunction.
So, the pathogenesis of the middle-ear cleft atelectasis is really pluri-causal!
Therapeutic management
Therapeutic management of the middle-ear cleft atelectasis involves a triple approach and concerns three entities: firstly, the general curative treatment of the upper airways mucosa inflammatory process, which is particularly important in children; secondly, the prospective curative treatment of the middle-ear cleft pressure variations imbalance; thirdly, the local curative treatment of the tympanic membrane pocket itself. The three areas which have to be taken into consideration simultaneously in the therapeutic management of the atelectatic ear are the upper air ways mucosa; mastoid, tympanic cavity and the fibrocartilaginous Eusta-chian tube; and the tympanic membrane pocket itself. This therapeutic management of the atelectatic ear is pathogenesis-oriented.
The general curative treatment of the upper airways mucosa inflammatory process
The general curative treatment of the upper airways mucosa inflammatory process must take into consideration the rhino-pharyngeal and sinusal mucosa disease which will be treated by way of antibiotics, anti- inflammatory, and anti- allergic drugs, either in loco, by spray, nose-drops, inhalations, aerosols, or generally, mostly orally. Adenoidectomy, or any surgical procedure in the sinus, will be performed, if necessary. In some cases, a stimulation of the immunity is proposed. The pharyngo- laryngal reflux of the gastric content occurs mainly during the night because of the fact that the superior sphincter undergoes a physiological relaxation during nighttime. The gastro-oesophageal and laryngo-pharyngeal reflux will also be treated, by the use of prokinetics drugs which prevent mechanical reflux or other drugs which reduce the chemical aggressiveness of the reflux either forming a protective gel on the surface of the acid gastric liquid – the principle of the ‘alginates’ – or neutralizing the acid of the stomach – the principle of the ‘anti-acids’, sealing off the production of acid by the gastric cells the ‘anti-secretory’ drugs. They contain two families, depending on their respective mechanism of action: Anti H2 and IPP, inhibitor for the protons pump.
Active or passive smoking as well as atmospheric pollution will be suppressed.
The prospective curative treatment of the middle-ear cleft pressure balance loss
Common medical language often evokes the essentials of a ‘well-ventilated middle ear’ while, in fact, a healthy middle-ear cleft is a poorly ventilated, but an intensely perfused middle-ear cleft. The normal balance of pressure variations in the middle-ear cleft depends on the one hand, on the transmucosal gas exchange between the middle-ear cleft and local mucosal blood (the middle-ear cleft includes tympanic cavity and mastoid); and on the other hand on the normal function of the fibro-cartilaginous Eustachian tube.
Treatment of the transmucosal gas exchange disturbances of the middle-ear cleft: tympanic cavity and mastoid gas cells system that are disturbed by the inflammatory process of the middle-ear cleft mucosa
The medical treatment is the same as for the upper airways mucosa, mentioned above. The surgical treatment consists of the curettage of the inflammatory granulation tissue and removing of the pathological post-inflammatory mini-partitioning in the middle-ear cleft. The ideal surgical procedure must acknowledge the need for eradication of all diseased mucosa while preserving the largest surface area possible of healthy mucosa as well as assuring regeneration and restoration of the physiological volume of the gas cell system. Chronic granulation tissue obstructing the aditus ad antrum has been found more frequently in patients with atelectatic ear. It must be removed by curettage. Because of the unhealthy status of the mastoid, opening is essential and permits drainage of the inflammatory secretion, removal of inflammatory granulation mucosa and creation of an enlarged gas reservoir. In contrast, the entire mastoid gas cell surface area is reduced after mastoidectomy, as the fine gas-cell walls are removed. Because the passive physiologic pressure buffer function may be partially governed by the mucosal surface area, it may not be desirable to remove all the gas cells when the mastoid contains healthy cells lined with thin normal mucosa. The posterior wall of the external auditory bony canal has to be preserved or reconstructed because it constitutes an impenetrable barrier giving the mastoid gas cell system the means of performing its function. Simple mastoidectomy is not sufficient. An antro-attico-mastoidectomy, taking care to preserve the scutum and the posterior bony canal wall, and, if necessary, completed with the posterior tympanotomy, must be performed with the aim of restoring the function of gas exchange to the postero-superior part of the middle-ear cleft.17
When surgical approaches to the middle-ear cleft are compared and considered it is important to remember that after a canal-wall-up procedure, the mastoid retains its native cuboïdal nitrogen-absorbing epithelium. An inflammatory process increases again both the number and the diameter of the blood vessels; thereby increasing the diffusion of gas. A slight compensated middle-ear cleft gas deficit – negative pressure – increases. Here too, it is no longer compensated and becomes pathological.
The canal-wall-down technique enables the removal of the nitrogen-absorbing mucosa of the mastoid. The new epithelial lining of the mastoid bowl is a stratified keratinizing epithelium. In canal-wall reconstruction, with mastoid obliteration, the removal of the nitrogen-absorbing mastoid epithelium and the obliteration with bone paté, decrease the likelihood of ‘negative pressure’ recurrence.
The mastoid obliteration techniques allow to reduce the function of transmucosal gas absorption in the middle-ear cleft and to reduce, in this way, the recurrence rate of the pathologies that lead to a ‘gas deficit’ in the middle-ear cleft. The main reverse of this surgical technique is the suppression of the buffer effect of this great gaseous area. But, what about the long-term complications of such a technique, including intracranial cholesteatoma and/or abscess. Even if regular controls are performed by accurate imaging of the obliterated mastoid cavity I remain sceptical.
Colleague surgeons too often think according to a mechanistic approach, conceiving the operated middle-ear cleft as permeated by gaseous flows. However, they must think along the lines of a physiologic approach as well. They must conceive the operated middle-ear cleft as a cavity which is covered by a mucosa through which gas diffusion occurs and where each gas nitrogen, oxygen, water vapour, has its own specific diffusion rate that influences the balance of pressure variations in the middle-ear cleft.
Treatment of the fibro-cartilaginous Eustachian-tube dysfunction
Eustachian-tube dysfunction may involve an abnormality at any stage of the dilatation cycle.18 Eustachian-tube dysfunction is characterized by the inability to equalize imposed pressure differences between the middle-ear cleft and the rhinopharynx. Eustachian tube dysfunction contributes consequently to a middle-ear cleft negative pressure. Eustachian-tube dysfunction is caused by neuro-muscular disorders in 8%, and by mucosal disorders in 92%.
Neuro-muscular disorders are excessive or too low contractions, lack of coordination of one or more muscles involved in the opening, dilating (tensor veli palatine) and closing processes of the fibrocartilaginous Eustachian tube. The neuromuscular disorders of the fibrocartilaginous Eustachian tube are constructively managed by logopedy, by a speech therapist. This therapy is based on the principle of neuro-muscular interaction and on the willpower of the patient. The patients must blow the nose, blow air directly into the ears using the Valsalva maneuver, close the mouth and breath through the nose, and activate the peritubal muscles by stimulating them with various types of exercises.
Mucosal disorders consist of inflammation of the mucosa, that give some obstruction of the tubal lumen, but also disorders of the ‘pressure’ and ‘gas mixture’ sensors of the entire system: middle-ear cleft and fibro-cartilaginous Eustachian tube.19 The mucosal disorders, and particularly the inflammatory process, will be treated by the triple way of medical, surgical and rehabilitative approaches.
The medical approach is just the same as the medical treatment of the inflammatory process of the upper air ways mucosa, explained above. Concerning the surgical approach, at present two surgical procedures are described clinically. Firstly, the laser Eustachian tuboplasty described by Oskar Kujawski and Dennis Poe that consists of an endoscopic transnasal-laser vaporization of inflamed mucosa and cartilage from the luminal posterior wall of the rhinopharyngeal orifice of tube. Indications are extremely restricted. Secondly, the ‘balloon dilatation Eustachian tube tuboplasty’ described by Holger Suddhoff, which has the great merit to attempt to treat in a non-invasive and so to say easy manner, the functional obstruction, situated at the level of the Eustachian tube isthmus.i
In order to manage a functional defect, a rehabilitative approach seems to be more logical and more clinically and scientifically based.
The rehabilitative approach consists of the use of the Kinetube®.20 The aim of this rehabilitative device, is to restore the normal behavior of the tubal opening, by generating a calibrated positive pressure in the rhinopharynx during swallowing. Kinetube provokes a kind of ‘massage’ of the ‘pressure’ and ‘gas-mixture’ sensors, at the rhino-pharyngeal orifice of the fibrocartilaginous Eustachian tube, that rehabilitate both central and peripheral nervous systems of pressure regulation in the middle-ear cleft, with retro-control between middle-ear cleft mucosa and the muscles of the fibrocartilaginous Eustachian tube.
Local curative treatment of the tympanic membrane retraction pocket
Therapeutic management of the tympanic membrane retraction pocket is a matter of detecting subtle changes and then assigning relative importance to the observed changes in a way that allows, to ear surgeon, to assess the risks and benefits of a proposed surgical procedure, compared with the risks and benefits of continuing approach without any surgical intervention.
Surgical management of the retraction pocket is controversial because the natural course toward choles-teatoma development cannot be predicted with certainty and hearing acuity remains normal until later in the disease course. Consequently, surgery is often delayed until there is clear indication, such as hearing loss or clear cholesteatoma development, but such delay often necessitates more extensive surgery. Because earlier intervention appears to be in the best interest of the patient,
Fig. 2. Curative management of the tympanic membrane retraction pocket, at level 2: surgical steps. (a) Implantation of a ventilating tube through any part of the tympanic membrane that still appears to be covering a ventilated part of the tympanic cavity; (b) Progressive suction of the atelectatic tympanic membrane to convert the retraction pocket into a lateral sac; (c) Pressure followed by: (d) Cutting of the edges of the lateral sac, to prevent eventual recurrence after tube extrusion.
I propose a staging system and a decision scale for therapeutic management of the tympanic membrane retraction pocket.
Local curative treatment of the pocket itself varies according to both the topography of the pocket and the evolutionary character of the pathological process.
Concerning the topography, 30% of the tympanic membrane retraction pockets belong to the pars flaccida and 70% to the pars tensa.
The evolutionary character of the pathological process is given by our classification of the tympanic membrane retraction pockets, based on clinical and tympano-microscopic findings. The quantitative as well as qualitative criteria, considered altogether in an evolutionary pathological character, define three levels of therapeutic management decision.
At the first level, the pocket is safe and stable. The risk for developing cholesteatoma is low. The histo-logical quality of the eardrum does not change with time. Hearing remains normal. The pocket is potentially reversible.
At the second level, the pocket is formed and uncertain. The risk for developing cholesteatoma is not clear. Morphological changes, such as progressively deepening retraction and/or drum hypotrophy, are observed over time; but hearing remains normal, unchanged over time.
At the third level, the pocket is unstable, characterized by adhesion to the surrounding structures, by erosion of the ossicular chain and bony frame, by a non-self-cleaning phenomenon which leads to accumulation of keratin, and by the presence of moist mucous polyps, indicating an additional local irritation.
The risk for developing cholesteatoma is very high. When the pocket is truly destabilized, cholesteatoma starts to evolve. Morphological changes are occurring or have stabilized with symptoms that may include otorrhea, bleeding and discomfort. Conductive hearing loss is usually present.
In case of local curative treatment of the pars tensa pocket, the pocket is the result of a locking of the anterior isthmus of the inter-attico-tympanic diaphragm. The postero-superior quadrant of the pars tensa becomes attracted in the direction of the retro-tympanum.
Level 1: the pocket is safe (44%). Treatment is conservative: regular cleaning of the eardrum and ear canal, by suction under an operative microscope, and, if necessary, with the aid of the endoscope.
Level 2: the pocket is uncertain (43%). We perform the excision of the atelectatic part which has become excessive, and we implant a tympanostomy tube through any part of the membrane that still appears to be covering a place where gas remains, ventilating the tympanic cavity.
The surgical steps are implantation of the tympanostomy tube, progressive suction of the atelectatic membrane to convert the pocket in a lateral sac (Fig. 2), pressure followed by cutting of the edges of the lateral sac, to prevent eventual recurrence after tube extrusion. In some cases, when the reverted sac is too flaccid, it may be necessary to raise the remnants of the tympanic membrane and partially dislocate the annulus from the bony sulcus. Healing is the usual evolution in less than eight days, tympanic membrane becomes again closed. Scarring is just the same as for traumatic perforation.21 Sometimes, if recurrence occurs, we turn to a CT scan of the mastoid for information concerning the pneumatization.
With a well-pneumatized mastoid, we need only to repeat the precedent procedure:
we add an antro-attico-mastoidectomy , taking care to preserve the scutum and the posterior bony canal wall. If necessary, we complete with a posterior tympanotomy.
Level 3: the pocket is unstable (13%). The fundamental cause is lack of the lamina propria of the drum. For this reason, the lamina propria has to be reinforced by conchal cartilage e.g., perichondrium composite graft), or better, replaced.
Personally, we replace it by a tympanic membrane allograft.21 Here too, a CT scan informs us about the pneumatization of the mastoid. Large cells: an allograft myringoplasty is sufficient; scanty cells: these call for the opening of the posterior cavities.ii
When necessary, we complete the reconstructive surgery with a two-hole ossiculoplasty: for this, the incus is remodeled and fitted in between the handle of the malleus and the mobile stapes; associated or not with a reconstruction of the posterior bony canal wall.22
Local curative treatment of the pars FLACCIDA pocket
The pocket is the result of a complete locking of both anterior and posterior isthmi of the inter-attico-tympanic diaphragm. The pars faccida becomes attracted into the epitympanum.
At Level 1, the pocket is safe and requires a conservative management.
At Level 2, the pocket is uncertain and must undergo the same conservative attitude consisting of a regular cleaning by suction under an operative microscope. Levels 1 and 2 contain 75% of the pars flaccida retractions.
At Level 3, the pocket is unstable and must receive a tympano-ossicular allograft tympanoplasty, with opening of the mastoid.
Middle-ear cleft acquired cholesteatoma
Definition
Middle-ear cleft cholesteatoma consists of the presence of a wrong stratified squamous epithelium in a wrong place: in the middle-ear cleft (Fig. 3). Cholesteatoma is characterized by an accumulation of desquamating keratinized epithelium and an osteolytic power.
Clinical observation indicates the moment when the transformation from tympanic membrane retraction pocket to cholesteatoma occurs. This happens when the pocket becomes fixed to the surrounding structures, starts to erode the ossicular chain and bony frame, is no longer self-cleaning, which leads to the accumulation of keratin, and shows humid mucous polyps, which indicates the presence of a secondary stimulus, irritating substances, additional local activity, or additional local inflammatory and/or infectious processes.
Fig. 3. Histological section through a middle-ear cleft cholesteatoma. (a) accumulation of desquamating keratinized epithelium; (b) The black rectangle points out a region of osteolytic power which is magnified in (3b).
From tympanic membrane retraction pocket to cholesteatoma24
Histological sections of the mucous polyps of a destabilized tympanic membrane retraction pocket show that the granulation tissue contains several inflammatory cells. Two main features occur: the accumulation of keratin, which is the result of the disappearance of the centrifugal keratin dispersion process, and the presence of large Langerhans’ cells, which are normally rare in a normal tympanic membrane and which are particularly numerous in cholesteatoma (Fig. 4). As we see in cases of cholesteatoma, Langerhans cells show an increased volume of numerous vacuoles and the loss of dendrites.
However, we know that cholesteatoma is the result of a conflict between stratified squamous and mucous epithelium. A similar conflict exists at the cutaneo-mucous junction of the tympanic perforation. Both situations coexist with a serious localized accumulation of inflammatory cells, which indicates that the cutaneo-mucous junction is not stable and its front can be considered an epidermal defect which is continually being renewed.
From the start of embryogenesis, the epithelium of the bottom of the external auditory canal is pushed forward by the power of aggressive growth.25 Parallel and concomitantly, this growth forward is regulated by control processes which put a brake on its forceful progression. Loss of the normal regulation of the growth of the squamous stratified epithelium takes place at the bottom of the external auditory canal, due to the secondary presence of an additional local stimulus such as, for example, irritating substances, or an additional local inflammatory and/or infections process, including a papillomavirus.
Fig. 4. Histological sections through a mucous polyp of a destabilized tympanic membrane retraction pocket. (a) General view. The black rectangle on the right side points out the accumulation of keratin which is magnified in Figure 4b; (b) The magnification of the section through the mucous polyp showed in 4a shows granulation tissue with several inflammatory cells and the accumulation of keratin.
There are two arguments which justify this loss of control of the growth of the squamous stratified epithelium. Firstly, this epithelium develops out of the middle-ear cleft, which is its normal anatomical site, and, consequently, the ‘contact-guidance’ phenomenon (described by Weiss26) does not exist there anymore.
Secondly, due to mucous-epithelial interaction, the inflammatory process produces a self-supporting immunological cycle, in answer to the conflict between cells and tissues.27 Bacterial proliferation and super-infection of the accumulated keratin debris form a biofilm that lead to chronic infection and epithelial proliferation.iii
The latter appears to be influenced by the cytokine-mediated inflammatory response.
Cholesteatoma derives from the epithelium at the bottom of the external auditory canal. This concept is based on the results of experimental works: the similar structure of the stratum corneum and the comparable biology. In the epithelium at both the bottom of the external auditory canal and at the level of the matrix of the cholesteatoma, the presence of identical growth factors, similar reactions to markers of epidermal differentiation, and identical cytokeratin expression, can be seen.
This cytokeratin expression is able to induce hyper-proliferation cell reactions at the level of the normal epithelium at the bottom of the bony canal, and is identical to their expression in the cholesteatoma matrix, contrary to that located in the cartilaginous canal, where their expression is almost non-existent. The stimulating action of the invasion process is the key to the transformation of the tympanic membrane retraction pocket into a cholesteatoma. This process acts as a stimulus to discharge the expression of cytokeratins of cell hyper-proliferation. In other words, the additional local irritation process triggers the keratinocytes at the bottom of the bony canal, leading to cholesteatoma.
Therefore, a tympanic membrane retraction pocket is a disease of the middle-ear cleft. Cholesteatoma should be considered as pathology of the squamous stratified epithelium at the bottom of the external auditory canal. This could, however, be two stages in the evolution of the same pathological process.
Therapeutic management
Medical management of cholesteatoma
At the present time, the treatment of cholesteatoma remains surgical. However, when it is proved to be impossible or when it must be delayed or to prepare surgery, the disease may be controlled for some time by repeated cleansing under the operative micro scope. Care must be taken to remove all impacted keratin debris. Hypertrophic granulation tissue may be controlled with a law-concentration solution of trichloroacetic acid carefully applied with a fine probe. Topical ear drops containing antibiotics and, if necessary, corticosteroids are used. Systemic antibiotics, based on culture results, may be necessary occasionally.
Surgical management of cholesteatoma
The modest goal of this part of this paper is to display, on the basis of our experience, the essential principles of the surgical management of cholesteatoma in adults and children.21 Surgical management of cholesteatoma remains controversial, with the main argument focusing on the surgical approach of the middle-ear cleft; in other words the surgical handling of the posterior bony canal wall.
The canal-wall-up procedure preserves the normal morphology of the ear canal, thus avoiding the necessity for periodic cleaning and the risk of bowl problems. The healing time is reduced. Hearing results may be better. A high cholesteatoma recurrence rate requires a post-operative control imaging or, if necessary, a second-look procedure.
The canal-wall-down procedure creates an open cavity after removal of the posterior bony canal wall. This widely exposes the epitympanum and mastoid, facilitating complete removal of the cholesteatoma sac and diminishing the recurrence rate.
The main disadvantages of this procedure are related to the necessity for periodic cleaning of the mastoid cavity. Subsequent bowl infections can occur, especially when the cavity becomes wet, causing significant lifestyle changes, particularly in the pediatric age group.
Surgical principles
In the surgical management of cholesteatoma, the important issue is not whether the technique should be an open or closed one, but the selection of a technique which allows safe but thorough eradication of the whole cholesteatoma. As far as we are concerned the main basic principles for the eradication of the cholesteatoma consists of absolute adherence to the following points.
Any ear suspected of cholesteatoma should be approached post-auricularly. The mastoid and the extent of the cholesteatomatous sac should be assessed from behind. A large retro-auricular combined approach allowing visualization of the whole middle-ear cleft is advocated in order to be able to totally remove the disease whatever its nature and its location.
The mastoid should be opened in a continuous horizontal plane, from the front of the attic to the tip of the mastoid. The whole mastoid and tympanic cavity should be opened at the same time, with particular attention for the sinus tympani and the anterior epitympanic recess.
The removal of the whole cholesteatoma will always be performed, from the mastoid and the attic towards the external auditory canal. The natural pathways along which the cholesteatoma develops in the middle-ear cleft should be treated in the reverse direction depending on the location of entrance through the tympanic membrane defect. The anterior attic penetration points or perforations essentially involve the attic, the epi-tympanum, the protympanum and even the whole mesotympanum. The posterior penetration points generally involve the facial recess, the antrum or the whole mastoid gas cell system. Only when the form and size of the cholesteatoma and its extensions are perfectly visualized should the removal be performed, using sponges and a bowl-shaped elevator to sweep the cholesteatoma from the mastoid or attic towards the external auditory canal (Fig. 5). This method allows a very soft and safe elevation, without any risk of breaking or rip ping up the matrix. Once the mass of cholesteatoma has been dissected free from around the cavities, it must be pushed away towards the external canal. When a bulky cholesteatomatous mass hinders the view and/ or prevents expulsion, it must be opened and its contents partly aspirated to avoid spontaneous rupture. The cholesteatoma sac, the drum remnants including the fibrous annulus, the connections between these and the matrix, and the granulation tissue should always be elevated laterally together with the meatal skin, excised and removed in one piece.
Fig. 5. Successive steps of the surgical management for cholesteatoma. (a) The dissection of the skin of the external auditory canal has to be performed as far as and including the annulus; (b) The mastoid and the extent of the cholesteatomatous sac must be assessed from behind. The whole mastoid and tympanic cavities are opened at the same time so that the cholesteatoma is approached by a double track: external auditory canal and mastoid; (c) Small balls of sponge and a bowl-shaped elevator are used to loosen the cholesteatoma and repress it in reverse direction of the natural pathways along which the cholesteatoma develops; (d) The cholesteatomatous sac is removed from the mastoid and the attic towards the external auditory canal; (e) The group consisting of the choles-teatomatous sac, the drum remnants including the fibrous annulus, the connections between these and the matrix, and the granulation tissue are elevated laterally together with the meatal skin; they are excised and removed in one piece; (f) The tympanic cavity, now completely free of cholesteatoma, is inspected and checked. Attention is turned to a perfect reconstruction of the bony annulus and/ or of the posterior wall. The restoration of the mesenchymatous barrier, between the squamous epithelium of the external auditory canal, of ectodermal origin, and the mucous epithelium of the middle-ear cleft of endodermal origin, should always be performed to abolish the risk of recurrence.
After eradication of the cholesteatoma, the restoration of the mesenchymatous barrier, between the squamous epithelium of the external auditory canal, of ectodermal origin and the mucous epithelium of the middle-ear cleft of endodermal origin, should always be performed to abolish the risk of recurrence.
Whatever the material used, the tympanic membrane should always be restored during the first stage. When and where necessary, any defect of the bony meatal wall is reconstructed.
Any malleus or incus harboring disease is removed together with the mass of cholesteatoma. Any diseased or suspected ossicle is replaced by a healthy one.
When there is a fistula, we remove the matrix of the cholesteatoma, only at the final time of the operation; afterwards, we seal, on the fistula, a piece of connective tissue, we stick a patch of tympanic allograft with fibrin glue.
Specific cases
Here we will consider the particularities of cholesteatoma in children, ‘attic’ versus ‘tensa’ cholesteatoma and ‘only one hearing ear’.
These principles for surgical management of cholesteatoma remain the same for adults as well for children. The age of the patients is not the most important factor.
The disease most frequently is unilateral, although chronic otitis media often is present in the opposite ear. What important is that there are more likely to be complications in children which demand urgent intervention. Fistulae are more frequent. Facial palsy is also encountered more frequently. Diagnosis and assessment of the extent of childhood cholesteatoma may be difficult because of lack of patient cooperation, small ear canal and meatus, and sometimes equivocal audiometric findings. CT scanning may be useful in establishing the limits of the cholesteatoma, and for medico-legal reasons. Usually, a precise assessment is achieved only by surgical exploration. Cholesteatoma is more aggressive and more invasive in children than in adults. There appears to be an increased incidence of residual and recurrent childhood cholesteatoma after surgical removal, when compared to adult disease. The hypothesis is that the biology of pediatric cholesteatoma may be different, more aggres sive. The activity of growth factors normally elaborated in childhood and absent in adult may play a role.
Other con tributing factors include: poor fibro cartilaginous Eustachian tube function, poor pneumatisation of the mastoid, poor maturity of the immune system, and frequent otitis media.
In our opinion, pars flaccida and pars tensa cholesteatoma belong to the same pathological process, although their localization and appearance are different. For this reason, the surgical approach is not modified and our therapeutic philosophy remains the same. In cases of pars flaccida cholesteatoma, pneumatization of the mastoid is generally preferable. The cholesteatoma appears in the form of a well-defined cyst, and the prognosis should therefore be better.
In the cases of an only hearing ear, we perform the most conservative management . Sometimes this entails regular review and control with microscopic suction toilet only. During the post-operative stage, the non Echoplanar Diffusion Weighted Magnetic Resonance Imaging (non EPDWI MRI), performed one and five years after the primary surgical event, excludes the presence of residual cholesteatoma in a non-invasive way, avoiding unnecessary second look surgery.iv
Conclusion
To summarize my attitude, concerning the surgical management of cholesteatoma, I will quote the following main points:
•Systematic post-auricular approach.
•Large opening of the mastoid gas cells system and the tympanic cavity.
•Repulsion of the cholesteatoma cyst via the natural pathways along which it had developed.
•Reconstruction of the mesenchymatous barrier between the squamous epithelium of the external auditory canal and the mucous epithelium of the middle-ear cleft.
References
1.Ars B. Tympanic membrane retraction pockets. Etiology, Pathogeny, Treatment. Acta Oto-Rhino-Laryngol belg 45:265–277, 1991
2.Ars B. Tympanic membrane retraction pocket. Acta Oto-Rhino-Laryngol belg 49:163–171, 1995
3.Ars B. Middle-ear cleft Atelectasis. In: Magnan J, Chays A (eds.), Cholesteatoma & Ear Surgery, pp. 279–293. Label Production Pub, 2001
4.Ars B, Ars-Piret N. Morpho-functional partition of the middle-ear cleft. Acta Oto-Rhino-Laryngol belg 51: 181–184, 1997
5.Ars B, Ars-Piret N. Morphofunctional partition of the middle-ear cleft. In: Ars B (ed.), Chronic otitis media. Pathogenesis-oriented therapeutic management, Amsterdam: Kugler Publications, 2008
6.Ars B, Ars-Piret N. Middle ear pressure balance under normal conditions. Specific role of the middle ear structures. Acta Oto-Rhino-Laryngol belg 48: 339–342, 1994
7.Ars B. Middle-ear cleft pressure regulation: Balance and imbalance of pressure variations. State of the art. In: Ars B (ed.), Chronic otitis media. Pathogenesis-oriented therapeutic management, pp. 113–127. Amsterdam: Kugler Publications, 2008
8.Ars B, Decraemer W, Ars-Piret N. The lamina propria and cholesteatoma. Clin Otolaryngol 14: 471–475, 1989
9.Ars B, Dirckx J, Decraemer W, Ars-Piret N. Faulty aeration of the middle ear: Repercussions on the tympanic membrane lamina propria. In: Sadé J (ed.), Proceedings of the Conference on the Eustachian tube and middle ear diseases, 26–29/10/1989, Geneva, pp. 365–371. Amsterdam: Kugler Publications, 1991
10.Kania R. Transmucosal exchanges in normal and pathological conditions. In: Ars B (ed.), Chronic otitis media. Pathogenesis-oriented therapeutic management, pp. 135–153. Amsterdam: Kugler Publications, 2008
11.Boedts D, Kuijpers W. Epithelial migration on the tympanic membrane. Acta Otolaryngol 85, 248–252, 1978
12.Boedts D, Ars B. Histopathological research on eardrum perforations. Arch Oto-Rhino-Laryngol 15: 55–59, 1977
13.Proops D, Hawke M, Blight A. The morphology of keratinocyte colonies derived from normal skin – migratory skin and choles-teatoma. In: Tos M (ed.), Cholesteatoma and Mastoid Surgery, pp. 429–432. Amsterdam/Berkeley/Milano: Kugler and Ghedini Publications, 1989
14.Ars B. Anatomic Variants as Catalyst Factor in the Pathogenesis of Otitis Media. In: Jahnke K, Fischer M (eds.), 4th European Congress of Oto-Rhino-Laryngology, Head and Neck Surgery, Berlin, 13–18/05/2000, ‘Past-Present and Future’, pp. 815–821. Bologna: Monduzzi Editore, 2000
15.Ars B. Pathogenesis of chronic otitis media; Local morphological predisposing factors. In: Ars B (ed.), Chronic otitis media. Pathogenesis-oriented therapeutic management, pp. 13–25. Amsterdam: Kugler Publications, 2008
16.Ars B. La partie tympanale de l’os temporal. Les Cahiers d’O.R.L., XVIII(6):439–523, 1983
17.Ars B, Dirckx J, Ars-Piret N, Buytaert J. Insights in the physiology of the human mastoid: message to the surgeon. J Internat Adv Otol 8(2):296–310, 2012
18.Ars B. Development of the fibrocartilaginous Eustachian tube. In: Ars B (ed.), Fibrocartilaginous Eustachian tube – Middle-ear cleft, pp. 43–48. The Hague: Kugler Publications, 2003
19.Ars B. Eustachian tube dysfunction. In: Sudhoff H (ed.), Eustachian tube. Bremen: Uni-MedScience, UNI-MED Verlag, Bremen, Germany, 2013 (in press)
20.Estève D. Re-adaptation of the baro-receptors of the fibrocartilaginous Eustachian tube and middle-ear cleft by means of the Kine-tube®, In: Ars B (ed.), Fibrocartilaginous Eustachian tube – Middle-ear cleft, pp. 202–207. The Hague: Kugler Publications, 2003
21.Ars B. Middle-ear cleft atelectasis. In: Magnan J, Chays A (eds.), Cholesteatoma & Ear Surgery, pp. 279–293. Label Production Pub., 2001
22.Ars B. Tympano-ossicular allograft tympanoplasty. In: Ars B (ed.), Chronic otitis media. Pathogenesis-oriented therapeutic management, pp. 273–283. Amsterdam: Kugler Publications, 2008
23.Ars B. Tympano-ossicular allograft tympanoplasty. Benefits, ethical and forensic aspects. In: Portmann M (ed.), Transplants and implants in otology III, Proceedings of the third International Symposium on Transplants and implants in otology. Bordeaux, France, June 10–14, 1995, pp. 121–126. Amsterdam/New York: Kugler Publications, 1996
24.Ars B. Pathogenesis of acquired cholesteatoma. In: Ars. B (ed.), Pathogenesis of cholesteatoma, pp. 1–18. The Hague: Kugler Publications, 1999
25.Michaels L, Sava S: Development of the stratified squamous epithelium of the human tympanic membrane and external auditory canal: the origin of auditory epithelial migration. Ann J Anat 184:334–344, 1989
26.Weiss P. Guiding principles in cell locomotion and cell aggregation. Exp Cell Res (suppl.) 8:260–281, 1961
27.Allen F. Molecular biology, biochemistry, genetics and animal models. In: Lim J (ed.), Recent Advances in Otitis Media, pp. 52–64. ISBN 0–9776 204–1-7, 2007
28.Poe D, Nashed Hanna BM. Balloon dilatation of the cartilaginous portion of the Eustachian tube: Initial safety and feasibility analysis in a cadaver model. Am J Otolaryngol-Head Neck Med Surg 32:115–123, 2011
29.Presti P, Linstrom ChJ, Silverman CA, Litner J. The poly-L-Lactide Eustachian tube stent: tolerability, safety and resorption in a rabbit model. Int Adv Otol 7(1):1–3, 2011
Address for correspondence: B. Ars, Avenue du Polo 68, B-1150 Brussels, Belgium. arsbernard@hotmail.com
Cholesteatoma and Ear Surgery – An Update, pp. 175–187
Edited by Haruo Takahashi
2013 © Kugler Publications, Amsterdam, The Netherlands
i. The balloon, once correctly positioned in both the cartilaginous and bony portion of the Eustachian tube, is inflated to a 20-mm length and a three-mm width, to a pressure of ten bars for two minutes. However, the following questions must be considered: Could you imagine that a only mechanic pressure, during two minutes, could solve a chronic inflammatory hypertrophy lasting for long, months and sometimes years? Or cure a long-standing muscular dysfunction? And, in practice, could such a mechanical surgical operation generate scars: fibrosis with the risk to transform a functional obstruction into an anatomic obstruction! Dennis Poe demonstrated that balloon dilatation of the cartilaginous portion of the fibro-cartilaginous Eustachian tube was feasible and appeared to be safe in a cadaver trial. Paul Presti demonstrated that the poly-L-lactide Eustachian tube stent was well tolerated by the test animals and completely resorbed at six months.
ii. The technique of tympanic membrane allograft implantation consists of both: total excision of the pathological membrane including the annulus. It is called myringectomy and allograft myringoplasty: replacement by a new tympanic membrane. In Belgium, we have a specific legislation which allows the benefit of allografts. In this situation, the tympanic allograft offers a double advantage: natural structure of the lamina propria, which gives to the epithelial cells the fitting directional impulse and rigidity of the membrane, due to the preservation in formaldehyde, which prevents recurrence of retraction.23
iii. A biofilm is a community of micro-organisms encased within a self-produced, extracellular, polymeric substance which is attached to the surface of the micro-organisms.
iv. Semantics about the eventual ‘second steps’: It is not always obvious whether a second operation, second stage or second look should be performed. A second operation may be undertaken by another surgeon in case of recurrent disease. ‘Second stage’ means that the surgical procedure is not completely finished, and that the surgeon has taken the deliberate decision to interrupt the procedure, which will be completed later after a specific period of time. In this case, the surgeon considers the intermediate period to be necessary to improve the condition or stability of the ear, before undertaking reconstruction. The decision for ‘staging’ could be based on pathological conditions and functional reasons. ‘Second look’ may be recommended by the surgeon when the surgical procedure is completely finished. As a precautionary measure, he decides to operate once more to exclude possible residual or recurrent pathologies. Second-stage and second-look procedures are, by definition, carried out by the same surgeon.