We investigated the tympanic membrane, temporal bone and ossicles by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy from 11 guinea pigs and from 2 human subjects aged 27 and 73 years old. And x-ray analysis of calcium deposits on the scanning electron microscopic photographs was also performed. We further studied the microstructure at the sites of attachment of the tympanic ring and the manubrium of the malleus to the tympanic membrane by TEM and staining with Alcian blue. Furthermore, a penetrating test was performed on the guinea pig tympanic membrane using a microtesting system to evaluate the dynamic properties of the membrane. At the margins of the tympanic membrane, fibers were observed running in various directions between the membrane and bone, and sporadic fibroblasts were seen among the fibers. Anchoring of cytoplasm to the bone tissue was observed at the region of the membrane in contact with bone. Fibers from the tympanic membrane also directly penetrated bone. These features were the same in both humans and guinea pigs. The margins of the tympanic membrane had the same type of attachment as bone and ligaments. However, at the area of attachment of the tympanic membrane to the malleus, concentric circles of collagen fibers made direct contact with bone and it was covered by the tympanic membrane. According to the penetrating test, a load required to rupture the tympanic membrane with the bone attached was less than that required for the extirpated tympanic membrane. The difference was related to the initial tensile force of the tympanic membrane. The tympanic membrane is sensitive to vibrations, but easily ruptured when external force is applied. The tympanic membrane appears to protect the inner ear by preventing the direct application of strong force to the inner ear.
In this paper, the clinical and basic studies were designed to understand the pathogenesis of attic cholesteatoma. Among 101 ears of 51 patients who had been treated at our OME outpatient clinic, the incidence of retraction pocket (RP) was 42.6% in OME group, which was statistically significantly higher than that of control (2.2%). All but one ear showed type A or Cl tympanogram, indicating normalized mesotympanum and CT scan revealed the clear attico-antrum. These findings indicated that RP persisting or developing after the resolution of OME was not caused by the disorder of surrounding structure but rather by the pars flaccida itself. The study of the epithelial cell kinetics in the pars flaccida of the tympanic membrane revealed that epithelial cells in the pars flaccida was smallest in shape and strongest in itscell proliferation activity in the entire tympanic membrane. This observation indicated that the pars flaccida bears very active generation of epithelial cells, which is likely to produce RP under some pathologic circumstances. As a matter of fact, immunohistochemical studies demonstrated that ICAM-1, EGF receptor, IL-6 receptors, and the increased density of Ki-67 antigen were present in the epidermis of inflamed cholesteatoma. Furthermore, high concentration of IL-1 and IL-6 were measured in cholesteatoma debris by ELISA. These findings indicated that cytokines were likely to play a role in the proliferation of epidermis of the pars flaccida to form cholesteatoma.
Histopathological and molecular biology studies were performed in relation to otitis media with effusion, atelectasis and adhesive otitis media as nonperforative lesions of the tense tympanic membrane. In otitis media with effusion, thinning of the lamina propria of the tympanic membrane was observed to have occurred as a result of absorption of the inner and outer fibrous layers. Eustachian tube insufficiency and damage to the middle ear mucosa can be postulated as causes of adhesive otitis media, and it was surmised that the difference between complete and partial adhesion of the tympanic membrane arises from differences in the time of occurrence or duration of eustachian tube insufficiency or differences in the intensity of reaction of the middle ear mucosa to inflammation. In addition, the posterosuperior region of the tympanic membrane is anatomically complicated, and retraction of the PSQ region leads to ready closure of the tympanic isthmus. Experimental findings also indicated that there was impairment of migration of the retracted and fused epithelium, which resulted in accumulation of debris, infection and activation of epithelial proliferation, with possible eventual progression to tension-type cholesteatoma.However, it is surmised that chaotic proliferation of the epithelium does not occur because of preservation of a normal balance between differentiation and apoptosis of the epithelial cells.
The healing process of human tympanic membrane perforations after trauma was observed under a microscope and was photographed in 30 ears. At the early stage of the healing process of perforations, the zone of hypertrophy of epithelium appeared on the central portion of the perfortion's margin and a thin membrane moved from the central portion of the perforation's margin towards the periphery. The healing pattern was classified into three groups. Type I showed that the perforation seemed to close from the central portion of its margin to the periphery in the same direction as the normal epithelial migration. Type I included 20 ears (67%). Type II showed that the perforation seemed to move and then was closed. Type II included eight ears (27%). Type III showed that the perforation seemed to close from peripheral portion of the perforation's margin to the center or to close from any portions of the perforation's margin. Type III included 2 ears (6%). The healing patterns in type I and type II showed that the perforation closed following the same directions of the normal epithelial migration. These findings demonstrated that epithelial migration plays a great role in the healing process of perforations.
Otitis media with effusion (OME) represents a spectrum of chronic disease states ranging from serous to mucoid otitis media. OME remains a common problem in the pediatric and geriatric population, but its etiology and pathogenesis are not fully understood. Several models using chinchillas, guinea pigs, and cats have been examined. In most of animal models, however, investigators are limited to the manipulation of experimental conditions and investigation of the individual relationships of various factors in the evolution of OME. In contrast, the mouse represents an ideal model for OME because of the availability of a wide variety of reagents. In this study, we made a murine model (BALB/c, male, 5 weeks) of long-term OME induced by a combination of injection with endotoxin into the bullae and eustachian tube blockage via an external surgical approach. Endotoxin induced effusion was produced using lipopolysaccharide from nonty peable Haemophilus influenzae. Mice were decapitated 3days, 2weeks, and 2months after surgery. In AB-PAS staining, compared to no treatment mice, the goblet cell population in the middle ear mucos a increased at 3 days and 2weeks after surgery in OME mice, but decreased significantly at 2months. In electron microscopy, the intracellular space was enlarged, and the tight junction complex was broken down in the animals at 2 months after surgery. This model should provide a necessary tool in the futher study of chronic OME.
Following classic radical mastoidectomy or modified radical mastoidectomy, the bone surface of the mastoid cavity is covered with skin-like tissue, which consists of stratifie flattened epithelium and underlying connective tissue. The skin-like tissue is often associated with chronic infection which continues for some decades. Surgical specimens of the skin-like tissue were taken from 9 ears and were investigated histologically. In addition, granulation tissue taken from 14 ears were examined. Skin-like tissue mainly presented chronic inflammation and signs of acute inflammation such as infiltration of neutrophils were not seen. Granulation tissue presented a mixture of acute and chronic inflammation. In addition, some granulation specimens presented particular findings not observed in skin-like tissue such as cholesterol cleft, multinucleated giant cells and deposition of hemosiderin. These observations suggest that removal of the skin-like tissue is necessary to terminate infection in the post operative mastoid cavity.
Nineteen cases of cholesteatoma with adhesive otitis media, operated on between 1993-1997. The mucosa of the inferior turbinate was transplanted to the medial wall of the middle ear, where mucosa was missing. The method of operation was canal down tympanoplasty with canal reconstraction. Six cases were treated by one stage operation and showed no recurrent adhesion in follow-up observation by microscope. Thirteen cases underwent staged operations, and there were no recurrence of adhesion except in only one case with cleft-palate. No recurrent cholesteatoma was occurred in all cases during the follow-up period. The middle ear mucosa, where the inferior turbnate mucosa was transplanted, was taken in 10 cases at the second stage operation. Histological investigations showed that 9 out of 10 cases showed the tranplanted mucosa, with either ciliary or cuboidal epithelia. One case showed connective tissue. Six out of ten cases revealed the tranplanted mucosa including the glandular tissue under the epithelium. It is considerd that this operative method is useful for preventing recurrence of adhesion by securing the middle ear cavity.
We evaluated the persistent tympanic membrane perforation following removal of ventilation tubes of 176 patients, 236 ears and 343 tubes: group I started insertion at 0-2 years old (35 children with 44 ears and 67 tubes), group II at 3-14 years old (90 children with 131 ears and 160 tubes), and young & adult group above 15 years old 51 people with 61 ears and 116 tubes. The persistent perforation was 6. 8% in Group I children, 6.9% in Group II children, and 24.6% in Group young & adult. One cholesteatoma grew from the edge of tube hole in the group II children. There was no correlation between the incidence of perforation and duration of intubation or frequency of insertions in this study. The problems during periods of tubing were CD irregular visits of the patient during periods of tubing, (2) inpatient of treatment, (3) otorrhea, (4) grarulation, and (5) thickening of membrane. The conditions at extrusion were (1) good, (2) spontaneous extrusion, (3) much scabbing, (4) infection and (5) enlargement of the tube holes etc. High perforation rates were shown in cases of irregular visits and/or extrusion due to enlargement of the tube holes in the young & adult group, and inpatient of treatment in Group I children and Group II children. It was concluded that periodical examination and treatment with a microscope, especially the inspection and cleaning the edge of tube holes was important to prevention of tympanic membrane perforation, and the early extrusion of tubes should be recommended if enlarged tube hole.
In two cases with cholesteatoma at the petrous part, surgery was carried out by middle cranial fossa approach. The present case showd a cholesteatoma penetrated into the brain through the periosteum of middle cranial fossa and the dura of the temporal lobe to cause an abscess. The treatment consisted of improvement of the general conditions by conservative measures including administration of antibiotics for cephalomeningitis, and removal of the brain abscess through the combined middle cranial fossa and mastoid antrum approach. In two additional cases, one with cholesteatoma spread extensively from the middle cranial fossa to the petrous part to cause facial paralysis, and the other with cholesteatoma extended to a wide area were presented. Both patients underwent surgery with the combined approach. In all cases, cholesteatoma was completely removed without postoperative complication, though the preservation of the preoperative hearing was failed in the third case.
Operative findings of four members of a family with an autosomal dominant inherited conductive deafness accompanied by hyperopia, broad thumbs, broad first toes, short distal phalanges, symphalangism and syndactyly were reported. Exploratory tympanotomy revealed the stapes ankylosis in all cases, ankylosis of incudostapedial joint in two cases and osseous fixation of the thickened crura to the promontory wall in two cases. Stapedotomy with the aid of a micro-drill system resulted in normal hearing in each case.
We report clinical efficacy of local application of 5-fluorouracil (5-FU) for the treatment of cholesteatoma. About 200mg of 5% 5-FU ointment was placed transmeatally on the surface of the lesions in 20 cases with various types of cholesteatoma (7 cases with attic type, 6 with external canal type, 3 with adhesive type and 4 with mastoid cavity problem) once to four times per month. The debris of cholesteatoma was decreased in all cases without any particular side effects. The effect was remarkable in cases with external canal type cholesteatoma and attic type cholesteatoma with positive mastoid aeration. This therapy is thought to be suitable for the primary treatment of these types of cholesteatoma.
A 11-year-old male presented with a hearing loss in the right ear and right facial palsy. Examination by CT and MRI showed a large acoustic neuroma which extended into the middle ear. The posterior quadrant of his right tympanic membrane was expanded due to the tumor. The tumor was surgically removed in a two staged operation, and the first operation was perfomed using the trans-labyrinthine approach and the second operation was done using the posterior cranial fossa approach. Even though the tumor had substantially destroyed the pyramis and extended into the inner and middle ear, the osseous labyrinth was still preserved. It is unusual that an acoustic neuroma was originated either in the inner ear or middle ear. We therefore postulated that the tumor might be originated in the internal auditory canal and thereafter expanded into the middle ear from the petrous cells and the inner ear windows.