Sade theory, he proposed that epithelial cells (prickle cells) of the pars flaccida could invade the subepithelial

tissue by means of proliferating columns of epithelial cells. Ruedi[146] supported this hypothesis with clinical and experimental evidence. For epithelium to invade into the lamina propria, the basal lamina (basement membrane) should be altered. Basal lamina disruptions now have been documented in human[102] [172] and animal[45] cholesteatomas. Huang and others [77] and Masaki and others[108] provided experimental support of this theory by demonstrating that epithelial ingrowth from the tympanic membrane can be induced by instillation of propylene glycol into the middle ear of chinchillas. These basal lamina breaks allow the invasion of epithelial cones into the subepithelial connective tissue and the formation of microcholesteatomas. This mechanism may explain some types of human cholesteatomas, even those occurring behind an intact tympanic membrane.[168] According to this theory, microcholesteatomas may enlarge and then perforate secondarily through the tympanic membrane, leaving the typical appearance of an attic cholesteatoma. This sequence of events has not been documented, although the alternations in the differentiation of keratinocytes and basal cell layer of cholesteatoma matrix have been observed in several studies. Abnormal distribution of epidermal differentiation markers, such as filaggrin and involucrin,[166] c-jun and p53 proteins,[162] and increased epidermal growth factor receptor,[24] [170] has been shown in middle ear cholesteatoma matrix. Increased CK 13 and 16, which are differentiation and hyperproliferation markers, were also found.[155] Kim and others[91] demonstrated the increased CK 13 and 16 expression in the area of the peripheral area of pars tensa of induced cholesteatoma by ear canal ligation and in the peripheral and central area of pars tensa of induced cholesteatoma by eustachian tube obstruction. Parisier and others [133] showed that fibroblasts in the subepithelium of cholesteatomas showed an invasive phenotype, whereas those from postauricular and ear canal skin were either weakly invasive or not invasive. In a similar study, Chole and others[37] found that normal fibroblasts and fibroblasts from induced cholesteatomas do not exhibit the invasive phenotype characteristic of a true neoplastic cell. Other lines of evidence support the basal cell hyperplasia/migration theory. Increased expression of human intercellular adhesion molecule-1 and -2 was demonstrated, which may play a role in cell migration into tissue.[25] The presence of heat shock protein 60 and 70 suggested the proliferation and active differentiation of basal keratinocytes associated with cholesteatoma.[163] There are some reports that immune response is involved in the hyperproliferative state of cholesteatoma epithelium.[170] [171] Langhan's cells may initiate immune reaction and promote proliferation of keratinizing epithelium by means of interleukin-1(IL-1).

Wendt[191] theorized that the simple squamous or cuboidal epithelium of the middle ear cleft could undergo a metaplastic transformation into keratinizing epithelium. Sad[148] [151] supported that theory, noting that epithelial cells are pluripotent and can be stimulated by inflammation to become keratinizing. According to this theory, an area of keratinizing epithelium within the middle ear would enlarge because of accumulated debris and contact with the tympanic membrane. With intercurrent infection and inflammation, the cholesteatoma would lead to lysis of the tympanic membrane and perforation, resulting in the typical appearance of an attic cholesteatoma. This theory is supported by demonstrating that biopsy

specimens from the middle ear of children with OME sometimes contain islands of keratinizing epithelium.[149] Some experimental evidence supports the contention that middle ear mucosa can become metaplastic and keratinize. Chole and Frush[39] showed that severe vitamin A deficiency leads to the formation of keratinizing epithelium within the middle ear and eustachian tube of rats. None of their experimental animals had cholesteatomas develop. Therefore, there is no direct evidence that cholesteatomas arise by squamous metaplasia of the middle ear mucosa. Clinically, it seems that each of these pathogenic mechanisms accounts for a proportion of acquired cholesteatomas. Regardless of the pathogenesis of aural cholesteatomas, they all share certain properties. Cholesteatomas are prone to recurrent infection, and they characteristically erode the bone of the ossicles and the otic capsule. Aural cholesteatomas originating from the vicinity of the tympanic membrane exhibit typical growth patterns into the temporal bone. Because most acquired cholesteatomas originate by invagination of the pars flaccida, their growth is limited by the mucosal folds and suspensory ligaments of the ossicles. The pars flaccida may invaginate into the lateralmost portion of the epitympanum (Prussak's space) and then into the recesses of the epitympanum posteriorly, lateral to the body of the incus, inferiorly into the middle ear by way of the pouch of von Trltsch ( Figure 133-8 ), or anteriorly into the protympanum.

Acute Mastoiditis Acute mastoiditis can develop when AOM fails to resolve. According to Luntz and colleagues,[19] acute mastoiditis exists when there are signs of AOM on otoscopy and local inflammatory findings over the mastoid process (e.g., pain, erythema, tenderness, auricular protrusion) or when the mastoid inflammatory changes coexist with roentgenographic or surgical findings of mastoiditis with or without evidence of AOM. Others insist on the concomitant presence of AOM, mastoid physical findings, and radiologic findings.[17] Luntz[19] reported results of a multicenter retrospective study of 223 such patients that provided valuable insight into the process. Twenty-eight percent of patients were under the age of 1 year at diagnosis, 38% were between 1 and 4 years of age, and 21% were between the ages of 4 and 8 years. Although one-third of patients experienced signs and symptoms of AOM immediately preceding the mastoiditis, two-thirds did not. Thirty percent of the patients had a history of recurrent AOM, and 5% (all of whom had recurrent AOM) had a prior episode of acute mastoiditis. One-third of the patients exhibited symptoms for 48 hours or less before diagnosis, and another third had symptoms for 2 to 6 days before presenting with acute mastoiditis. Spontaneous tympanic membrane perforation occurred in less than one-fourth of patients; the tympanic membrane was bulging or erythematous in two-thirds. Twenty-two percent of the patients presented with complications on admission, the most common of which was subperiosteal abscess, followed by meningoencephalitis, and an occasional case of facial paralysis, labyrinthitis, or a central nervous system complication. Despite parenteral antibiotics, 8% of the patients who had been free of complications on admission developed complications of acute mastoiditis during hospitalization. Again, the most common was subperiosteal abscess, but three patients

developed intracranial complications and two developed facial paralysis while receiving parenteral antibiotics. One-third of patients required surgery because they had extracranial or intracranial complications on admission, failed to exhibit satisfactory clinical improvement, or developed complications despite adequate antibiotic treatment during hospitalization. Bak-Pedersen and Ostri[1] reviewed the records of 79 Danish patients who underwent acute cortical mastoidectomy for acute mastoiditis between 1977 and 1997. All patients had erythema and swelling and pain over the mastoid associated with a current or recent episode of AOM that did not improve after 24 to 48 hours of intravenous antibiotics. Patients admitted with intracranial complications of mastoiditis were excluded. The average age in their series was 16 months, and the average duration from the onset of disease (AOM) until admission for acute mastoiditis was 9 days. Only one-third of the patients exhibited an asymptomatic interval between their AOM symptoms and the mastoiditis. Both of these studies established that acute mastoiditis is a disease of the very young, and they dispel the classic notion that acute mastoiditis develops only after an asymptomatic period of 3 to 4 weeks. Van Zuijlen and colleagues[32] pointed out another interesting feature of acute mastoiditis. In countries such as the Netherlands, where it is unusual to prescribe antibiotics as first-line treatment for AOM, the incidence of acute mastoiditis is considerably higher than in countries where antibiotics are routinely prescribed for AOM. The lower overall cost and decreased incidence of allergic reactions to antibiotics resulting from withholding antibiotics in routine cases of AOM must be weighed against the increased likelihood of mastoiditis and other complications. Coalescent Mastoiditis Etiology. Sometimes, when a patient has AOM and mastoiditis that persist unabated for 2 to 4 weeks, coalescent mastoiditis develops. This is an acute progressive clinical infection with corresponding changes in the bone and mucoperiosteum of the mastoid air cell system. Coalescent mastoiditis is a disease of the young, especially of boys. Most patients are 4 years old or younger when they contract this disease. Bacterial virulence and decreased host resistance are important in its etiology, but mastoid development also plays a role. The condition rarely develops in children who have had chronic ear disease or in those with poorly pneumatized mastoids containing few air cells. Rather, it tends to occur in patients with well-developed air cell systems that contain numerous small pneumatic spaces and in those who have had little or no previous otologic disease. Pathology. Initially, hyperemia and edema of the mucoperiosteal lining of the mastoid air cells block the narrow aditus and disrupt aeration. The mucous membrane thickens, and impaired ciliary function prevents normal middle ear drainage through the eustachian tube. The serous exudate becomes purulent as inflammatory cells accumulate. Continued inflammation, hyperemia, and accumulation of purulent debris result in venous stasis, localized acidosis, and decalcification of the bony septae. The osteoclastic activity in the inflamed periosteum softens and decalcifies the bony partitions, causing the small air cells to coalesce into a larger cavity.[3] Pathophysiology.

As the infection grows, pressure within the mastoid cavity increases, and conditions become progressively more favorable for the infection to extend beyond the confines of the mastoid. In the presence of intense inflammation and infection, phlebitis and periphlebitis are common and spread the infection to the adjacent meninges, sigmoid sinus, cerebellum, and the temporal lobe.[24] The infection sometimes extends directly to the meninges, sigmoid sinus, labyrinth, or facial nerve because of bone erosion. The most common pathway for infection to extend beyond the mastoid is through the lateral cortex behind the ear. Less commonly, it can extend to the soft tissues in the upper portion of the neck (see section entitled "Bezold Abscess") and, rarely, to the soft tissue anterior and superior to the auricle either by direct extension through eroded bone or by phlebitis and periphlebitis. Go and colleagues[7] reviewed the records of 118 children with acute mastoiditis at Texas Children's Hospital between 1986 and 1998 and found only eight patients in whom the mastoiditis had caused an intracranial complication. Diagnosis. The symptoms of coalescent mastoiditis (purulent otorrhea, fever, toxicity, and ear pain) are the same as those seen in patients with uncomplicated AOM. The strongest historical suggestion of coalescent mastoiditis is the chronology of the infection in which purulent drainage or significant otalgia persists for 2 or more weeks, recurs after 10 to 14 days, or significantly worsens after that time interval. As a group, children with coalescent mastoiditis look sicker and have more toxicity with higher-temperature and more persistent fevers than those with AOM. Older children may be able to localize the pain to the postauricular area rather than the ear canal. Physical findings that are most helpful include mastoid tenderness to percussion, mastoid erythema, and sagging of the posterior superior external auditory canal wall. The clinician should order a complete blood count and hematologic studies followed by CT scanning, which can establish the diagnosis by documenting the breakdown of the bony cell walls and opacification of the pneumatized spaces ( Figure 134-1 ). If any suggestion of an intracranial complication exists, the clinician should obtain an enhanced MRI scan. Treatment. The treatment for coalescent mastoiditis can be either medical or surgical. Without question, complete mastoidectomy with ventilating tube placement in conjunction with appropriate antibiotic therapy provides prompt, precise eradication of all infected tissue in an expeditious and cost-effective manner. This is the most conservative management of this potentially serious complication. From : Cummings Mastoidectomy. An incision is made behind the ear where the ear connects with the head. Through this incision specialized drills and a microscope are used to remove all infected material. This includes the cholesteatoma, if present. Once all the infection has been removed, the surgeon will decide whether the ear is appropriate for an ear bone reconstruction at the time of mastoidectomy. Sometimes, a second-look is needed four to six months later. The second-look allows the ear to heal and scar tissue to mature prior to placing the small ear bones. If they are placed too soon, then they may not heal correctly and result in some hearing loss.

Even with microscopic removal of the cholesteatoma, there is a rate of recurrence of approximately 15%. Children, in particular, have aggressive acting cholesteatomas and may indeed need further surgery to remove the cholesteatoma and improve the mastoid condition. In aggressive mastoiditis or cholesteatoma cases, a canal-wall-down procedure may be needed. In this case, the natural configuration of the ear canal is removed and the mastoid is opened to the ear canal. From the outside, this is not really appreciated, but using a speculum and looking through the ear canal a physician can determine that a canal-wall-down procedure has been performed. The reason a mastoid canal-wall-down procedure is performed is to limit the space where cholesteatoma or mastoiditis could reside. Therefore, the recurrence rates are lowered. A disadvantage of the canal-wall-down mastoidectomy is that the natural ossicular chain is usually disrupted by this operation. Thus, it is a balance between removing the underlying progressive disease and sacrificing hearing function. The hearing function can either be recreated through hearing aid usage or by an ear bone ossicular reconstruction.

From : http://www.eardoc.us/otology.php?box=7

MODIFIED RADICAL MASTOIDECTOMY A modified radical mastoidectomy is most commonly performed for congenital or acquired cholesteatoma, chronic suppurative otitis media with mastoiditis, or both. The mastoid cavity, the epitympanum, and the external canal are exteriorized into a common cavity, but the tympanic membrane is either maintained or grafted. In a study of 232 Pittsburgh children with cholesteatoma, there were 244 surgical procedures, of which 24% were modified radical mastoidectomies.4 A Bondy modified radical mastoidectomy was performed in selected cases (eg, small, constricted mastoid) in which cholesteatoma was localized to the epitympanum and lateral to the ossicles. Today, however, a canal wallup tympanomastoidectomy, if possible, is preferred over a modified radical mastoidectomy for cholesteatoma (see Cholesteatoma later in this chapter). When chronic suppurative otitis media and mastoiditis fail to improve following intensive medical management, a tympanomastoidectomy is usually the next step in management (see Tympanomastoidectomy later in this chapter).5 If, during surgery, there appears to be a persistent obstruction between the middle ear and the mastoid cavity when the simple mastoidectomy is completed (ie, irrigation fluid fails to flow freely between the two areas), then the canal wall may have to be removed and the operation converted into a modified radical mastoidectomy. An alternative would be a posterior tympanotomy approach to the facial recess, but this technique is not as effective in controlling and preventing the infection as removing the canal wall. An alternative to removing the posterior canal wall in a child would be to remove the incus. Neither removal of the posterior canal wall nor the incus is desirable in a child, thus the surgeon should make every effort to be conservative by removing as much disease (eg, granulation tissue) as possible from the facial recess and attic, to promote adequate drainage from the aditus ad antrum and mastoid into the middle ear. Indications

 Cholesteatoma: When the disease extends to the mastoid air cells and cannot be effectively managed using the more preferred method of an intact canal wallup tympanomastoidectomy (see Cholesteatoma later in this chapter) Chronic suppurative otitis media and mastoiditis: When nonsurgical methods fail and a simple mastoidectomy will most likely be, or has been, unsuccessful in providing adequate aeration between the middle ear and the mastoid cavity.

CHOLESTEATOMA Classification and Etiology Aural cholesteatoma can be congenital or acquired. Congenital cholesteatoma is caused by a congenital rest of epithelial tissue within the middle ear (including intratympanic), or in other portions of the temporal bone, which may appear as a white cyst-like structure or as sheets of tissue. The tympanic membrane is usually intact, and the cholesteatoma is apparently not a sequela of otitis media or eustachian tube dysfunction; however, Tos6 recently proposed that a congenital cholesteatoma may be acquired and may be a sequela of otitis media. The most common site of congenital cholesteatoma, in the early phase, is within the middle ear in the anterosuperior quadrant of the mesotympanum. Disease frequently extends into the anterior attic, or into the posterosuperior portion of the mesotympanum, and can also invade the facial recess, sinus tympani, and the attic. Also, the site can be in the posterosuperior portion of the mesotympanum. More advanced congenital middleear cholesteatoma can extend into the aditus ad antrum, mastoid, petrous apex, labyrinth, and can even spread outside the temporal bone, such as into the intracranial cavity. The tympanic membrane may not be intact if the disease is extensive. Acquired cholesteatoma can be a sequela of middle-ear disease or may arise from implantation of epithelium, caused by trauma or surgery (ie, iatrogenic) of the middle ear (including the tympanic membrane), ear canal, or mastoid. Acquired cholesteatoma can be present anywhere in the middleear cleft, can extend to any portion of the temporal bone, and can spread outside the temporal bone. Often the cause of the cholesteatoma, either congenital or acquired, is uncertain, especially when the disease is far advanced and the tympanic membrane is not intact. Of 232 children operated on at the Childrens Hospital of Pittsburgh between 1973 and 1990, 43 (18%) had a congenital cholesteatoma (excluding intratympanic), 83 (36%) had an acquired cholesteatoma, and in 106 (46%) children, the cholesteatoma could not be distinguished as either congenital or acquired.4 Of 59 children who had a cholesteatoma treated in Switzerland between 1981 and 1996, 18 (29%) were congenital and 41 (71%) were acquired.7 Cholesteatoma Surgery in Children vs. Adults The ideal goals of surgery for cholesteatoma in children are similar to those in adults: 1. Eradicate disease 2. Preserve or reconstruct the anatomic structures 3. Preserve or restore hearing 4. Prevent residual and recurrent disease Many surgical procedures have been advocated to achieve these goals, but, unfortunately, none have been subject to randomized clinical trials. The lack of rigorously designed trials relates to many factors, but primarily to the variation in site, extent, and severity of the disease, and the rather limited

number of pediatric cases at any one individual center. As well, most otologic surgeons have their own preferences based on their skills, training, and experience. Therefore, controversy remains over the optimal procedures to treat and prevent residual cholesteatoma (disease remaining after surgical attempts to eradicate it) and recurrent cholesteatoma (development of new disease). Canal WallUp vs. Canal WallDown Mastoidectomy Controversy exists over whether to perform a canal wallup or canal walldown procedure when the extent of cholesteatoma requires mastoidectomy. In infants and children, every effort should be made to avoid a canal walldown mastoidectomy because it is especially desirable to maintain or reconstruct the anatomy in this age group. Among the many disadvantages of having a potentially life-long open mastoid cavity, is the fact that children usually require a general anesthetic for the periodic cleaning and debridement that ensues. The cavity is more difficult to clean postoperatively for children than in adults because children are frequently apprehensive during the procedure. Furthermore, since swimming is a common activity in youngsters, they are more susceptible to infection when an open mastoid cavity is exposed to water. Therefore, whenever possible, perform a canal wallup tympanomastoidectomy and additional tympanoplasty, if needed. Since the middle ear and mastoid are not directly visible following these procedures, a second look operation is performed approximately 6 months later to detect any residual cholesteatoma. Exploration is recommended at 6 months because cholesteatoma is more aggressive in children than adults. Waiting 12 months, as advocated for adults, can result in more extensive residual disease than is desirable. If a residual cholesteatoma is encountered at the second look, it is removed and the child is re-explored in another 6 months. These repeat procedures are performed until there is no further residual cholesteatoma. In our study of 232 children who had 244 surgical procedures, residual or recurrent cholesteatoma developed in 38% of cases and 23% of those cholesteatomas were detected at the time of the second look procedure.4 Residual or recurrent disease was significantly associated with ossicular erosion at the time of the original surgery, in direct proportion to the number of ossicles involved. In a Japanese review of children operated on for cholesteatoma, residual cholesteatoma was uncovered at the second look tympanotomy in 64% of cases.8 During the second look exploratory tympanotomy this author uses the 70 Hopkins rod-lens telescope to inspect the middle ear for residual and recurrent disease. Currently, a canal walldown mastoidectomy is performed for: 1. Suppurative complications (intratemporal or intracranial) of cholesteatoma, with cholesteatoma in the mastoid. The decision for or against removing the canal wall, however, should be individualized, based on the site, extent, and severity of the complication, as well as other factors below. 2. Cholesteatoma in inaccessible areas (by transmastoid approach) of the temporal bone, such as the retrolabyrinthine region or the petrous apex. 3. Children with another medical condition (eg, severe congenital heart disease) which would make a re-operation (eg, second look tympanotomy) a potential health hazard. 4. Children who are unable (eg, living in remote areas) or unlikely (eg, poor compliance) to return for a second look tympanotomy. This applies not only to developing countries, but also to certain populations in the United States. 5. Second look procedures revealing aggressive extensive residual

cholesteatoma that is unlikely to be controlled in the future without a canal walldown procedure. From : http://societyformiddleeardisease.org/SurgicalAtlasofPediatricOtolaryngology/5Mastoidectomy-and-Cholesteatoma.pdf