Ménière's disease: endolymphatic sac decompression compared with sham (placebo) decompression.

The placebo effect in surgery for Ménière's disease was investigated in a double-blind, controlled surgery by comparing the effect of a regular endolymphatic shunt with the effect of a purely placebo operation (regular mastoidectomy). Thirty patients with typical Ménière's disease participated in the study. They were selected for surgery because of unsuccessful medical treatment and were chosen randomly for each treatment group. The patients filled in daily dizziness questionnaires for 3 months before and 12 months after surgery, registering nausea, vomiting, vertigo, tinnitus, hearing impairment, and pressure in the ears. The patients were operated on in two university ENT departments. Those operated on in one department were controlled each month at the other department, and vice versa. At the termination of the trial, the investigators as well as the patients gave their overall opinion of the efficacy of the operation. Minor differences could be demonstrated between the active and the placebo group, but the greatest difference in symptoms was found when comparing pre- and postoperative scores, in which both groups improved significantly.

Gastrin, cholecystokinin and their precursors in acoustic neuromas.

Using sequence-specific radioimmunoassays the occurrence of 4 neuropeptides (cholecystokinin (CCK), gastrin, somatostatin, substance P and some of their precursors) was examined in 19 human acoustic nerve tumors and corresponding normal tissue. The normal acoustic nerve tissue obtained by autopsy contained traces of CCK, somatostatin, and substance P (less than or equal to 0.5 pmol/g), but neither proCCK, gastrin nor progastrin. In contrast 8 tumors expressed proCCK (range 0.2-4.5 pmol/g), 3 tumors gastrin (0.1-7.3 pmol/g) and 14 tumors progastrin (0.6-2.2 pmol/g). Traces of somatostatin were present in two and substance P in one tumor. The results show that acoustic neuromas often express the homologous CCK and gastrin genes, but process their propeptides poorly to transmitter-active peptides. The tumor synthesis of gastrin/progastrin contrasts to the rare, sporadic expression of the gastrin gene in normal nerve tissue.

Mucous glands in the developing human rhinopharynx.

In 42 fetuses and prematures, the entire mucosa from the rhinopharynx was stained by various whole-mount methods. The development, growth, spread, distribution, situation, and size of the glands were determined. The development starts in the 11th week below the tubal orifice, whence the glands spread to the entire rhinopharynx. The number increases gradually by about 60-70 glands a week. By the 23rd week, there are 1,100-1,200 glands in the rhinopharynx. After that juncture, there is presumably no further new formation. The density and size of the glands were at a maximum in Rosenmüller's recess, below the tubal orifice, and in the salpingopharyngeal fold, least anterior to the tubal orifice and at the junction to the pharynx. The role of the sero-mucous glands in the rhinopharynx under normal and abnormal conditions is dicussed.

A new pathogenesis of mesotympanic (congenital) cholesteatoma.

OBJECTIVES: To introduce a new, acquired pathogenetic theory of mesotympanic cholesteatoma behind an intact eardrum in children and to present some doubts on congenital pathogenesis. STUDY DESIGN: Literature review. METHODS: The incidence and origination of mesotympanic cholesteatoma in children were thoroughly analyzed in the world literature and correlated to the histopathological studies on human middle ear epithelia and to epidemiological studies on secretory otitis, tubal occlusion, and acute suppurative otitis media. RESULTS: The new, acquired theory is based on the fact that that the place of origin of the anterosuperior mesotympanic cholesteatoma is the area of the malleus handle and malleus neck, and of the posterosuperior cholesteatoma, the long process of the incus. During the common pathological conditions there is a great risk of retractions and adhesions of the eardrum to these ossicles. After subsequent loosening of the retracted eardrum some cells of the keratinized squamous epithelium may be left behind and become included into the tympanic cavity, eventually causing an inclusion cholesteatoma. Four basic mechanisms of inclusions are proposed and the presence of great dynamics in middle ear disease in children, with high incidence of tubal dysfunction, retractions, secretory otitis, and acute suppurative otitis, is documented, making the acquired pathogenesis probable. The place of origin does not fit with the congenital pathogenesis of epithelial formation localized on the lateral wall of the eustachian tube close to the annulus. The origination around the malleus and incus fits better with the proposed acquired pathogenesis. CONCLUSIONS: There are no definitive proofs for the acquired pathogenesis of the mesotympanic cholesteatoma, nor is there experimental research to prove or disprove it. Mesotympanic cholesteatoma, congenital cholesteatoma, acquired pathogenesis of mesotympanic cholesteatoma, cholesteatoma in children, cholesteatoma behind intact eardrum.

Density of goblet cells in chronic secretory otitis media: findings in a biopsy material.

In 30 ears from 24 children with chronic secretory otitis the density of goblet cells and of glands was determined on biopsies from the anterior part of the promontory. The goblet-cell and gland density proved to be highly increased in all cases, with marked individual variations. The median density of goblet cells was 142 cells/field, corresponding to 8,000 cells/mm-2. This substantiates the fact that in chronic secretory otitis the mucous secretion is a product of goblet cells and mucous glands and confirms the secretory pathogenesis of the disease.

Origin of nasal polyps.

The nasoethmoid complexes from 6 patients with nasal polyps were systematically examined. First, the location and place of the origin of the polyps were recorded and photographed. The polyps and their places of origin were removed, serial sectioned, and examined. In all 6 patients, the polyps originated from the nasal mucosa. Most of the polyps extended laterally from the mucosa into the anterior part of the middle meatus. Several polyps originated from the mucosa near the ethmoid cell ostium or directly from the mucosa lining the edge of the ostium. The ostia themselves were not blocked by the polyps, and there was no indication of polyp formation in the ethmoid cells.

Penicillin reduces new bone formation in acute otitis media.

OBJECTIVE: Previous studies have shown that acute otitis media alters modeling dynamics in bone tissue structures surrounding the middle ear cavity. Initial resorption is followed by formative activity, which is seen as massive osteoneogenesis. However, neither resorptive nor formative activity occurs in the otic capsule, supporting the theory on existence of a perilymphatic barrier of specialized bone. STUDY DESIGN: To investigate the effect of penicillin administration on the pathological bone modeling in acute otitis media, we employed a rat model of acute pneumococcal otitis media. METHODS: Five rats were sacrificed on postinoculation days 4, 8, 16, 90, and 180, preceded by oral administration of penicillin V 100 mg/kg per day, initiated on day 2 and lasting 5 (2) days. Using a light microscope, bone histomorphology was registered and the thickness measured in four well-defined localities, followed by comparison with a previous study of untreated animals. RESULTS: Measured bone thickness was unaffected by treatment on day 4, but significantly reduced in two localities on day 8 and in all localities on following days of sacrifice. Bone cytomorphology and histomorphology were otherwise unaffected by penicillin administration. CONCLUSION: Penicillin reduces new bone formation in acute otitis media, leaving other features of histomorphology unchanged.

Nasal polyps: epithelium and goblet cell density.

The density of goblet cells was determined in 14 anterior and 15 posterior nasal polyps using the whole-mount method. The specimens were then serial cut and the type of epithelium was determined in nine localities in each polyp. The goblet cell density was correlated to the epithelial type. Pseudostratified, cylindrical epithelium was the prevailing type, occurring in 62% of anterior localities and 78% of posterior localities. Transitional types of epithelium were found in 33% of the anterior and 19% of the posterior localities. Stratified squamous epithelium occurred in 5% and 3%, respectively. The goblet cell density was highest in hyperplastic pseudostratified epithelium, whereas it was four times lower in transitional epithelium and even lower in squamous epithelium. Marked differences in the distribution of epithelium and goblet cell density were found between anterior and posterior polyps, illustrating that the epithelium constantly changes under the influence of air current, contact with other polyps, infection, growth, and age of the polyp as well as other unknown factors.

Postinflammatory acquired atresia of the external auditory canal: treatment and results of surgery over 27 years.

Postinflammatory, acquired atresia of the external auditory meatus is a relatively rare consequence of chronic otitis media or recurrent external otitis with an annual incidence of 0.6 cases per 100,000 inhabitants. Primary and late results after operative treatment of this condition in 53 ears over 27 years are presented. Perioperative findings are described, and an outline of applied surgical technique is given. Six patients had bilateral involvement. The male-to-female ratio was 1:2, median age at surgery was 46 years, and the median follow-up period was 5 years (range, 4 mo to 13 y). In 11% of the cases, recurrent atresia developed. Early operation is recommended, because cholesteatoma behind the atresia was found in 9%. Hearing improvement has been considerable after removal of the atresia with primary closure of airbone gap within 20 dB in 90% of the cases.

Treatment of secretory otitis and pneumatization.

In 33 children, median age 4 years, with bilateral secretory otitis, adenoidectomy was performed, a grommet was inserted in the right ear, and paracentesis was done on the left side. Seven years postoperatively x-rays were taken of the children's mastoid cell systems and these were measured by planimetry. A significantly larger cell system was found on the side with grommets, which is considered to support the environmental theory of pneumatization.

Autologous tissue seal in myringoplasty.

A prospective, controlled study on the efficacy of autologous tissue seal in myringoplasty was performed. In 29 patients with dry perforations, temporalis fascia was glued with tissue seal. In 30 patients the fascia was fixed with Gelfoam balls. No significant differences in take-rate was found between these two methods.

Incidence of vestibular schwannomas.

OBJECTIVE: To determine the incidence of vestibular schwannoma (VS) in Denmark in a period of 191/2 years. STUDY DESIGN: Retrospective review of prospective registered data on all patients with VS operated on by the translabyrinthine, lateral suboccipital, or middle cranial fossa approach, as well as patients who were allocated to the "wait-and-scan" group. METHODS: Charts were reviewed and tabulated for age, extrameatal tumor extension, and date of diagnosis. The available data were divided into three periods: June 1976 to June 1983, July 1983 to June 1990, and July 1990 to December 1995. RESULTS: The number of newly diagnosed tumors in the first period was 278, corresponding to an incidence of 7.8 tumors/million population per year; in the second period 337, corresponding to an incidence of 9.4 tumors/million population per year; and in the third period 355, corresponding to an incidence of 12.4 tumors/million population per year. A significant increase in incidence of the newly diagnosed intracanalicular tumors in the second and third periods was observed. CONCLUSION: The increase in incidence of VS can probably be explained by the awareness among otolaryngologists of the diagnosis of VS and better access to computed tomography and magnetic resonance imaging scans. The observed increase in the diagnosis of the small and intrameatal tumor creates a clinical dilemma, whether to operate on tumors in this early stage or to allocate patients to the wait-and-scan group. This problem will still be relevant in the upcoming years, since the incidence of intrameatal and small VS is expected to increase.

Histopathology and growth pattern of cystic acoustic neuromas.

In a series of 571 acoustic neuromas, 23 were identified as cystic tumors. An immunohistochemical study including nervous system-associated protein (S-100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), laminin, fibronectin, vimentin, factor VIII (von Willebrand factor)-related antigen, and the nuclear antibody Ki-67 was performed. The cyst walls contained numerous S-100-positive fibrils distributed throughout the whole extent of the walls. Laminin, fibronectin, and vimentin were predominantly located around the vessel walls, factor VIII was found inside the vessels. GFAP-positive lamellae occurred in 50% of the cases near the surface of the cyst walls. Ki-67 is an antigen associated with cell proliferation. The density of Ki-67-positive cells was found to be 36 times lower in 16 noncystic controls than in the 23 cystic neuromas, indicating that the increase in tumor size in cystic acoustic neuromas may be caused by expansion of the cysts and not by an actual increase in the growth rate of the tumor cells. The data achieved in this series may contribute to better planning of the surgical approach. Because of the risk of sudden expansion of cystic elements, a wait-and-see policy should not be applied to patients with cystic acoustic neuromas.

Sinonasal papillomas: a report of 82 cases in Copenhagen County, including a longitudinal epidemiological and clinical study.

The present epidemiological and clinical study comprises 82 patients with sinonasal papillomas diagnosed from 1975 to 1993. Histology showed 58 cases of inverted papillomas including 5 cases of associated carcinoma, 19 cases of exophytic papilloma, and 5 cases of columnar cell papilloma. The incidence of sinonasal papillomas in Copenhagen County was 0.74 per 100,000 inhabitants per year. The inverted and columnar cell papillomas were typically located in the middle meatus with a varying degree of involvement of the adjacent sinuses. The exophytic papillomas were predominantly located multicentrically on the nasal septum. Good results of treatment, especially with regard to inverted papillomas, were not correlated to the aggressiveness of surgery. A lateral rhinotomy with medial maxillectomy was performed as primary surgery in 28 patients. In 50% of these patients there were recurrences. The preliminary results of endonasal endoscopic surgery revealed a high success rate, i.e., no recurrences in 5 cases so far. The septal papillomas were typically resected by a simple endonasal procedure. There were recurrences in 66% of these cases. The midfacial degloving procedure may be advocated instead of or as a supplement to the lateral rhinotomy if the tumor cannot be visualized sufficiently by endoscopy. Smoking may dispose to sinonasal papillomas.

Pathogenesis of middle ear adhesions.

Middle ear adhesions are well-known to the ear surgeon, although data on etiology, pathogenesis, and significance are lacking in current literature. This study on experimental acute otitis media presents histopathological data on these aspects. Pneumococci were inoculated in the right middle ear bulla of 25 rats; the left ear served as control. At days 4, 8, 16, 90, and 180, respectively, 5 rats were decapitated, and the bullae were removed, opened, and stained with periodic acid-Schiff (PAS)/alcian blue. The entire middle ear mucosae were dissected from the bone, embedded as whole mounts in colophonium chambers, and examined by light microscopy. Representative parts of the mucosae were sectioned and examined in the same way. All inoculated ears from day 8 and later (20 in total), contained mucosal adhesions of various sizes, shapes, and locations. None were found in control ears. The site of predilection for the development of adhesions was the hypotympanum, followed by the anterior epitympanum, the attic, the drum, the interossicular spaces, and the tubal orifice. Based on present histopathological findings, we conclude that the middle ear adhesion is a pathological phenomenon caused by infection, and we propose a six-stage hypothesis of pathogenesis: 1. Localized epithelial rupture; 2. Prolapse of subepithelial tissue; 3. Epithelialization of the prolapse; resulting in a polypous/fold-like prominence; 4. Growth and elongation of the prominence; 5. Fusion of the end/tip of the prominence with another part of the mucosa; 6. Formation of an adhesion.

Inverted papilloma of the nasal cavity: pathological aspects in a follow-up study.

The initially removed tumors from 42 patients with inverted papillomas of the nasal cavity and paranasal sinuses were subjected to an extensive histopathological examination in order to define the characteristics associated with multiple recurrences and development of malignancy. Two of the patients subsequently developed squamous cell carcinoma and eight patients had more than one recurrence. No specific histological characteristic was determined to be a predictor of multiple recurrences or development of malignancy. However, three patterns of characteristics emerged from the data which were found to be related to the development of malignancy, multiple recurrences, and benign behaviour. Malignancy was found to be associated with bilateral inverted papilloma, a predominance of mature squamous epithelium, the presence of all three epithelial types (metaplastic squamous, mature squamous, and cylindrical), severe hyperkeratosis, a mitotic index greater than or equal to 2 per high-power field (HPF), absence of inflammatory polyps among the papillomas, an abundance of plasma cells, and an absence of neutrophils. Multiple recurrences (without malignancy) were associated with a mitotic index greater than or equal to 2 per HPF and an absence of inflammatory polyps. Benign behaviour was associated with predominantly mucinous tumors, a mitotic index less than 1 per HPF, a ratio of neoplastic epithelium/connective tissue stroma greater than or equal to 6, and the presence of inflammatory polyps among the papillomas.

Vestibular schwannoma growth: the continuing controversy.

OBJECTIVE: To investigate the growth of vestibular schwannoma (VS) in a series of 123 patients with 127 tumors allocated to the "wait and scan" group in the period 1973-1999. STUDY DESIGN: Retrospective review of prospectively registered data on all patients with VSIE from the entire country who were allocated to the wait and scan group. METHOD: Clinical charts, audiometric data, and neuroradiological images were reviewed and tabulated for age, hearing level expressed as speech reception threshold (SRT) and speech discrimination score (SDS), maximum extra-canalicular tumor extension, and possible changes in tumor diameter. The material was updated three times (in June 1993, June 1996, and June 1999). Via the Danish national register, data on whether the included patients were alive or dead were collected in 1999. RESULTS: The tumor growth, growth rate, and growth patterns were calculated in three periods 1973 to 1993 (mean observation period, 3.4 y), 1973 to 1996 (mean observation period, 3.8 y), and from 1973 to 1999 (mean observation period, 4.2 y). By termination of the first period, 94 tumors (74%) exhibited measurable growth, 23 tumors (18%) no measurable growth, and 10 tumors (8%) revealed negative growth. By the end of the extended observation period, tumor growth was observed in 104 tumors (82%), no tumor growth in 15 tumors (12%), and negative growth in 8 tumors (6%). Subsequent to the third observation period, growth was observed in 108 tumors (85%), no growth in 11 tumors (9%) and negative growth in 8 tumors (6%). However, the results may also be interpreted in another way: 52 patients (42%) were alive at the time of writing, tumor growth did not demand any intervention, 23 patients (19%) died as a result of non-tumor-related causes, and 35 patients (28%) were previously treated and alive by the termination of the third observation period. CONCLUSION: Depending on the observation period, three sets of growth results were obtained. The long observation period, updating and re-updating the results, gave us the opportunity for a de novo interpretation of the results and the long-term consequences of the wait and scan policy. Combined with other factors, the achieved results should be considered when timing of surgery is to be decided.

Bone modeling dynamics in acute otitis media.

OBJECTIVE: A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown varying degrees of both osteoresorption and osteoneogenesis. This study presents data on the dynamics of bone modeling in a rat model of acute pneumococcal otitis media, studied longitudinally from day 1 through 6 months after inoculation. RESULTS: Qualitative, as well as quantitative histopathology revealed initial osteoresorption, followed by increasing apposition of new bone in the middle ear cavity, initiated at the outer periosteum. Measured bone thickness in four anatomically distinct locations peaked 3 months after inoculation, followed by some degree of normalization. However, bone thickness was still massively increased 6 months after the acute incident. Except in perilymphatic spaces of the otic capsule, resorptive and formative activity were found in all bone tissue structures surrounding the middle ear cavity, including the bony external auditory canal and the ossicles. CONCLUSION: These findings may support the existence of a perilymphatic barrier of specialized bone and suggest that even a single episode of acute infection may alter properties of ossicular chain conduction. The authors conclude that acute otitis media is accompanied by massive and progressing net osteoneogenesis, already evident at 3 days and peaking 3 months after inoculation, followed by some degree of normalization. This is conceivably in support of the environmental theory of mastoid pneumatization, claiming inflammatory disease as the cause of a sclerotic mastoid.

The early stages of polyp formation.

The purpose of this study is to describe polyp formation in the mucosa of the middle ear as a possible model for the pathogenesis of nasal polyps. In 65 Wistar rats, the eustachian tube was occluded on the left side for up to 20 months; 60 right-sided, nonoccluded ears served as controls. Following occlusion, the middle ear mucosa was examined for signs of polyps. Signs of polyp formation or fully developed polyps were seen in 14 (22%) of the middle ears, and were only seen in middle ears with signs of actual or previous infection. It was established that the first stages of polyp formation include epithelial rupture, proliferation of fibrous tissue through the epithelial defect, and epithelialization of the prolapsed fibrous tissue by proliferation and migration of epithelial cells from the surrounding epithelium until there is full epithelial covering of the polyp. This report discusses whether the described middle ear model may form basis for the explanation of the pathogenesis of nasal polyps.

Treatment of sinus cholesteatoma. Long-term results and recurrence rate.

We classified cholesteatomas as attic cholesteatoma, developing from Shrapnell's membrane; tensa cholesteatoma, originating in pars tensa, which is subdivided into tensa retraction cholesteatoma involving the entire pars tensa, and sinus cholesteatomas, developing from a posterosuperior retraction (perforation). From 1964 to 1980, one-stage operations were carried out on 271 ears with sinus cholesteatomas. Follow-up included 90% of the patients, and the median observation time was 9.75 years. The recurrence rate was 10%. The recurrence rate was found to be independent of the mastoidectomy type employed. The best hearing results were obtained in ears with intact ossicular chain. We conclude that, wherever possible, sinus cholesteatoma should be removed through the auditory canal without mastoidectomy just as an intact ossicular chain should be preserved. "Canal wall up" and "canal wall down" appear to be equally valuable mastoidectomy types, and both methods must be employed to obtain optimum results.