Expression of transforming growth factor-beta 1 and alpha-smooth muscle actin of myofibroblast in the pathogenesis of nasal polyps.

The pathophysiology of nasal polyps remains unclear, but recent work suggests that many cytokines are produced in nasal polyps (NPs) and that they may play various important roles in the pathogenesis of NPs. Transforming growth factor-beta 1 (TGF-beta 1), secreted by many inflammatory cells, is a potent inducer of myofibroblasts. Myofibroblasts express alpha-smooth muscle actin (alpha-SMA) and a source of extracellular matrix (ECM). In this study, we investigated a potential link between inflammation and the growth process in human NPs. Sixteen patients who were affected by NPs and who had undergone functional endoscopic sinus surgery were included in this study. Nasal mucosa of inferior turbinate (NM) of 10 patients who had received rhinoplasty or turbinectomy for other disease was used as the control. alpha-SMA and TGF-beta 1 were detected using immunohistochemistry and the number of labeled cells were counted (alpha-SMA and TGF-beta 1 indices). The expression of alpha-SMA and TGF-beta 1 indices found in NPs and NM was compared using Student's t-test. In our study, alpha-SMA and TGF-beta 1 indices were found to be significantly higher in nasal polyps than in nasal mucosa. TGF-beta 1 produced by inflammatory cells can influence the development of myofibroblasts which in turn can induce extracellular matrix accumulation and, therefore, TGF-beta 1 plays a important role in the formation of nasal polyps.

A prospective study of p53 expression and its correlation with clinical response of radiotherapy in nasopharyngeal carcinoma.

OBJECTIVES/HYPOTHESIS: Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs in people in the southeastern Asian area, including Taiwan. The significant association of p53 expression in NPC suggested that p53 overexpression seemed to occur at an early stage in the development of NPC. Alterations of p53 status were probably the most commonly encountered in head and neck carcinomas, and there was extensive evidence that p53 status might determine tumor response to therapy. Ionizing radiation was studied extensively for the relationship between its damaging effect and p53 status in human cancer cells. STUDY DESIGN: This study was carried out to investigate whether there was any correlation between overexpression of p53 protein and locoregional tumor response in patients with NPC treated with 7000 cGy of radiotherapy. METHODS: Sixty-eight patients (50 males, 18 females) with NPC who were diagnosed and treated with radiotherapy were studied prospectively. Before they had received a radiation dose of 7000 cGy in 35 fractions, five fractions a week, p53 status from a nasopharyngeal biopsy was studied using immunohistochemical staining (IHC). RESULTS: The locoregional response rate of primary tumor was analyzed statistically. Forty-seven patients (69.1%) showed positive p53 staining in their tumors. There were 5 positive stains in 6 squamous cell carcinomas (SCC; 83.3%), 34 positive in 53 non-keratinizing carcinomas (NKC; 64.2%), and 8 positive in 9 undifferentiated carcinomas (UC; 88.9%). The mean ages for patients with three different histopathologies were 48.5, 46.1, and 61.1 years. There were 8 patients (7 positive stains, 1 negative stain) with residual tumor after radiotherapy and all were NKC (6 males, 2 females). Therefore, the clinical response rate of primary tumor was 85.1% in positive p53 immunostaining (40 of 47 cases), 95.2% in those with no immunostaining (20 of 21 cases); the former was poorer in locoregional tumor response than the latter, but there was no significant difference (P > .05, chi2 test). CONCLUSIONS: We conclude that there is no statistically significant correlation in locoregional response of primary tumor between p53 overexpression and radiotherapy in patients with NPC (P > .05, Fisher exact test).

Evaluation of proliferative activity in middle ear cholesteatoma using proliferating cell nuclear antigen.

Middle ear cholesteatoma has a remarkable invasive activity accompanied by destruction of ossicles and temporal bone. Its aggressive growth and high tendency to recur have impact on the postoperative care of the patients. Proliferating cell nuclear antigen (PCNA) is a 36 KDa DNA-delta-polymerase-associated protein whose level of synthesis has been found to correlate directly with rates of cellular proliferation. In this present study, we used ABC (avidin-biotin complex) technique and monoclonal antibody to PCNA to evaluate the expression of PCNA in 37 cases of cholesteatoma epithelium and 21 cases of normal postauricular skin. The rate of PCNA-positive cells in basal, parabasal, and upper layer of cholesteatoma epithelium tissue is 78% (29 cases), 68% (25 cases), and 41% (15 cases). In each layer of the postauricular skin tissue is 71% (15 cases), 67% (14 cases) and 34% (7 cases). No statistical difference of expression of PCNA-positive cells exists between each layer of cholesteatoma epithelium and normal postauricular skin; however, a tendency of higher PCNA-positive cells in cholesteatoma epithelium was observed. Immunohistochemical method of PCNA has the advantages of spatial architecture preservation, the relative simplicity of the methodology and the rapid acquisition of results. Although the etiology and histopathology of the growth pattern and osteolytic activity of cholesteatoma are unclear, information on cell kinetics may assist in cholesteatoma classification and may help predict the risk of recurrence and bone destruction. The results of this report indicate that cholesteatoma has a similar proliferative activity to the normal postauricular skin, and cholesteatoma itself is not a real tumor, despite its clinical behavior, which is similar to neoplastic cells. It is necessary to further study whether the cell kinetic information we obtained from the PCNA immunohistochemical analysis provides a valuable tool in accessing the prognosis of the cholesteatoma.

Tissue polypeptide antigen, carcinoembryonic antigen, carbohydrate antigen, and CA125 levels as tumor markers in squamous cell carcinoma of the head and neck.

Ninety-eight untreated patients with squamous cell carcinoma of the head and neck of different localizations (larynx 36, oral cavity 48, nasal cavity 14) were selected for a study to measure TPA, CEA, CA 19-9, CA125 pre- and post-therapy. Fifty healthy individuals and 42 patients with benign lesions were as normal and disease controls. The positive rates were 22.3%, 27.8%, 5.6% and 0% respectively in TPA, CEA, CA 19-9 and CA125 markers in laryngeal cancer patients. The positive rates of TPA level was higher with significant difference in advanced stage group than in early stage group; conversely, the positive rate of CEA levels were somewhat high in early stages of laryngeal cancer. Meanwhile, the positive rates were 25.0%, 18.8%, 14.6% and 4.2% individually in the same order in oral cancer patients. There was no relationship between the marker levels and progression of the oral cancer. The tumor markers were almost of no use in detecting nasal cancer. It also seemed there was no relationship between the various serum levels and the tumor or nodal burden in laryngeal and oral cancer. Only TPA level decreased significantly after therapy in patients with laryngeal and oral cancer who had originally elevated marker levels. Conclusively, only TPA and CEA markers are of some clinical use in the disease.

The probability of diagnosis of nasopharyngeal carcinoma in patients with only adult-onset otitis media with effusion.

This study tried to assess the probability of nasopharyngeal carcinoma (NPC) being present in adults with only otitis media with effusion (OME) and evaluate the necessity of nasopharyngeal biopsy in Taiwanese adults with only OME. The clinical features of patients with known OME were analyzed and the incidence of nasopharyngeal carcinoma in adults with only OME was assessed. The clinical features of 36 adults with OME but without other symptoms and signs suggestive of NPC who presented to the Kaohsiung Medical College Hospital Department of Otorhinolaryngology between December 1995 and February 1997 were analyzed. Two of these patients had biopsy-proven non-keratinizing carcinomas. OME was caused by upper respiratory infection in 8 patients (22.2%), chronic paranasal sinusitis in 5 (13.9%), allergic rhinitis in 5 (13.9%), NPC in 2 (5.6%), other etiologies in 5 (13.9%) and by unknown etiologies in 11 (30.5%). The incidence of NPC in adults with OME but no other symptoms and signs suggestive of NPC was 5.6% (2 out of 36 patients). It was higher than other reports because NPC has a high prevalence in Taiwan. Therefore, biopsy of the post-nasal space in adults with only OME when NPC is strongly suspected is necessary for the early diagnosis of NPC in Taiwan. We conclude that Taiwanese adults with only OME for which the cause is unclear should be subjected to an examination and biopsy of the nasopharynx to exclude NPC.

Lymphoepithelial cyst of the parotid gland--a case report.

The lymphoepithelial cyst has been commonly termed branchial cleft cyst or branchial cyst. Although many theories, including the branchial apparatus theory, thymic duct theory, and inclusion theory, have been put forward, the etiology is still controversial. Parotid lymphoepithelial cysts are rare and could be divided into two groups, AIDS-related and non-AIDS related, by the relationship with HIV infection. A non-AIDS related lymphoepithelial cyst of left parotid gland in an 81-year-old man presenting as a parotid tumor is described. A left partial parotidectomy was carried out to remove the lesion. There was no recurrence after 2 years. Lymphoepithelial cysts of the parotid gland are often misdiagnosed as other benign tumors in spite of detailed preoperative investigations. Thus a pathological proof is needed for precise diagnosis. In addition, we also need to take the possibility of HIV infection into consideration, although Taiwan is not an AIDS epidemic area.

Age and the prognosis of tympanoplasty type I.

The purpose of this study is to evaluate the influence of the age factor on the prognosis for tympanoplasty type I. One hundred subjects (41 males, 59 females, 16-65 years old, mean age 37.9 years old) who accepted tympanoplasty type I during a four-year period were reviewed. The success rate of the surgery was analyzed using the three criteria suggested by the Japan Clinical Otology Committee. In addition, linear regression was used to analyze the correlations between age and pre-operative hearing, post-operative hearing and hearing gain. Using the proportion of patients with a postoperative hearing threshold within 40 dB as the criterion, the 16-25 year-old group had the best results (80%) and the 56-65 year-old group had the worst results (66.7%). Using hearing gain exceeding 15 dB as the criterion, the best result was for the 36-45 year-old group (60.9%), and the worst result was for the 56-65 year-old group (26.7%). Using post-operative air-bone gap within 20 dB as the criterion, the best result was for the 16-25 year-old group (70%), and the worst result was for the 56-65 year-old group (40%). The best total success rate was for the 16-25 year-old group (80%) and the worst was for the 56-65 year-old group (66.7%). The total average success rate was 74%. Linear regression analysis showed that the postoperative hearing thresholds increased significantly with advancing age. But there was no statistically significant difference in hearing gain between the various age groups and the preoperative hearing thresholds also increased with advancing age. In conclusion, although tympanoplasty type I offered the patients a similar hearing gain among the different age groups, from the point of view of social function, it offered younger people a better chance of social hearing than the elderly and a higher surgical success rate. The poor postoperative hearing of the elderly was a result of their poor preoperative hearing condition.

Sensorineural hearing loss in MELAS syndrome--case report.

A mitochondrial tRNA mutation at nucleotide 3,243 is known to be found in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). We report a 30 year-old female patient of MELAS, diagnosed 5 years ago, who presented herself to our ENT outpatient department because of her bilateral tinnitus and progressive hearing impairment since 4 years ago. Two sequential pure tone audiograms showed bilateral symmetrical progressive sensorineural hearing loss, especially in the high frequency area in 1993 and 1996. The pure tone average was R-45 dB, L-47 dB in 1993 and R-62 dB, L-67 dB in 1996. Hearing loss is an important feature in MELAS syndrome and reported to be seen in about 30% of patients. It is often the first clinical symptom, too. In any case, mitochondrial cytopathies need to be considered by the otologist in forming a diagnosis of sensorineural hearing loss (SNHL), particularly in cases, which present adult-onset progressive hearing loss and neurologic symptoms before 50 years of age.

Management of labyrinthine fistula in middle ear cholesteatoma.

Labyrinthine fistula is a complication of chronic otitis media with cholesteatoma. Canal wall down tympanoplasty with partial mastoid cavity obliteration and complete removal of cholesteatoma matrix was adopted in five cases of labyrinthine fistula. The operation resulted in elimination of vertigo. Sensory hearing has been saved in two cases. Air conduction hearing improved in one case. In three cases whose air conduction deteriorated post-operatively, bone conduction worsened in two cases and remained unchanged in one case (Tympanoplasty type 0 was performed in the other one case.) During the follow-up period, otorrhea improved in all cases and there was no evidence of recurrence of cholesteatoma. If the hearing of the other ear is acceptable, we suggest one-stage canal wall down tympanoplasty with complete removal of cholesteatoma matrix and partial mastoid cavity obliteration. It provides low recurrence rate of cholesteatoma and there is no need of re-operation.

Detection of EBV in tumor tissue and peripheral blood by polymerase chain reaction in patients with nasopharyngeal carcinoma.

Sixty-nine untreated patients with a pathologically verified nasopharyngeal carcinoma were selected for the study of detection of EBV in nasopharyngeal tumor and peripheral blood by polymerase chain reaction (PCR). Primers were directed to conserved regions of EBV genome encoding capsid protein gp 220 (Bam HI L region). A distinct 239 bp band of the PCR products indicated the presence of EBV. Results showed that EBV DNA was obtained in 91.3% of 69 NPC patients and 16.7% of 18 healthy individuals on nasopharyngeal tissue, and the difference was statistically significant between the above two groups. Nevertheless, no EBV DNA was verified from the mononuclear cells of the peripheral blood of the two groups. There was no relationship between the positive EBV DNA and the titer of serological markers. Meanwhile, the positive EBV DNA did not show any relationship with the histology type, tumor and nodal bulk, or even metastasis. Although a high positive rate of EBV DNA was detected in nasopharyngeal tumor of patients, additional environmental and genetic factors must still be considered.

Pneumocephalus in a case of nasopharyngeal carcinoma.

An extensive mass involving the skull base was found in a 49-year-old male patient with nasopharyngeal carcinoma. Deteriorating neurologic status developed 2 weeks after radiation to the nasopharynx with the initial dosage of 5480 cGy and boosted dosage of 3520 cGy. Computerized tomography revealed multiple foci of air occupying the subarachnoid space, and an air-fluid level was found in the lateral ventricle. Antibiotics and conservative treatments were administered to the patient and consciousness returned gradually. Unfortunately, he died of hypovolemic shock owing to massive bleeding from the nasopharynx 7 days later.

Nasal septal cyst--a case report.

The usual complications of submucous resection of the nasal septum (SMR) are septal hematoma, infection, hemorrhage, septal perforation, and nasal deformity. We present a case of nasal septal cyst which may be a rare complication of SMR. Entrapment of free nasal mucosal remnants or inward folding of incised septal mucosa is thought to be the cause. The patient underwent deroofment of the left cystic wall by lateral rhinotomy. There was no recurrence after one year.

Significance of tumour markers in nasopharyngeal carcinoma.

Ninety-two nasopharyngeal carcinoma (NPC) patients were selected for a study to measure tissue polypeptide antigen (TPA), CA 125, CA 19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP). In all, 32 patients with chronic ENT disease and 40 healthy persons were asked to participate as diseased and normal control groups. The results showed (1) TPA was the most effective of all markers; (2) CA 125 was less useful, but had a definite correlation with TPA; (3) CA 19-9, CEA, and AFP were nearly useless; (4) the TPA level increased with advancing tumour, nodal stage, and stage groups; (5) when metastases occurred, the TPA level was extremely high; (6) the TPA level decreased significantly after irradiation at stages II, III, and IV, but increased at stage V; and (7) there was no difference in TPA level between the nonkeratinizing and undifferentiated carcinomas. This study demonstrated that the TPA marker was useful in determining the degree of NPC severity and especially for indicating the presence of metastatic disease.

Bacteriology of maxillary sinuses in rabbits.

To study whether normal sinus flora exist in normal sinus, we used 40 sinuses from 20 New Zealand white rabbits as the animal model. The histological examination was performed on sinus mucosa from each sinus and bacteria from these sinuses were cultured. Surprisingly, 70% of them (28 sinuses) were found to have sinusitis. These sinuses not only contained bacteria in culture but also showed various degree of histological inflammatory reaction in mucosa examination. Of the other 12 normal or near normal sinuses, only two showed positive bacterial culture, and ten of them showed negative bacterial culture either from discharge or mucosa studies. Accordingly, these data suggest that these two studies (bacterial culture and histological mucosa examination) are consistent. Thus, from this study it was concluded that there is no bacteria or few bacteria in normal sinus.

Suture technique to correct caudal septal deviations.

The traditional submucosal resection of the septal deviation (SMR) is a good method to correct septal deviations, but it is not useful for treating either caudal end deviations or deformities from posterior septum to caudal ends. There have been several methods proposed to correct caudal end deviations, and Ellis's suture technique is considered to be the most effective and convenient one after many years of implementation. Our department has selected 18 cases of caudal end deviations for application of Ellis's suture technique in recent years. Sixteen of the 18 cases have been followed for at least one year, two of them for less than a year. The results are very satisfactory. This article is meant to present the outcome.

Increased production of tumor necrosis factor-alpha and release of soluble CD4 and CD8 molecules, but decreased responsiveness to phytohemagglutinin in patients with nasopharyngeal carcinoma.

Twelve patients with nasopharyngeal carcinoma (NPC) were studied for spontaneous and phytohemagglutin (PHA)-stimulated production of cytokines, soluble markers and [3H] thymidine incorporation by mononuclear cells. The same number of patients with skin cancer and healthy subjects were used as control groups. Our results showed that the NPC group produced much more tumor necrosis factor-alpha (TNF alpha), soluble CD4 (sCD4) and CD8 (sCD8) in PHA-stimulated mononuclear cell supernatants than those in the other two groups. The levels of soluble interleukin-2 receptor (sIL-2R) and gamma-interferon (IFN gamma) in PHA-stimulated supernatants were at the same high level in the NPC and healthy subjects groups while the concentrations were much lower in the skin cancer group. We also noticed that the early stage group in NPC patients had higher levels of interleukin-1 alpha (IL-1 alpha), TNF alpha, IFN gamma and sIL-2R in both spontaneous and PHA-stimulated mononuclear cell supernatants. The stimulation index of PHA-responsiveness was 155, 5.2 and 37, respectively, in the healthy subjects, skin cancer and NPC groups. The PHA-responsiveness was depressed in both the NPC and skin cancer groups. It seems that cancer patients have an impaired T cell mitogenic response after mitogen stimulation. NPC patients had better immune response than skin cancer patients in immune factor release or PHA-responsiveness.

Pseudocyst of the auricle: steroid therapy.

We have seen 13 cases of pseudocyst of the auricle in the past two years (1990-1991). Twelve of the 13 cases that were treated with needle aspiration and intralesional steroid injection are reviewed retrospectively. The results were quite satisfactory. In 10 cases, the cystic swelling disappeared without recurrence after such treatments. The remaining 2 cases were lost to follow-up after the first steroid injection. This method of treatment did not cause side effects or discomfort in our study. We also reviewed and analyzed 36 other cases of this cyst we have seen from 1986 to 1989.

The mucoceles or pyoceles of the paranasal sinuses.

Fifty-five mucopyoceles in 53 patients were diagnosed during the 10-year period from 1982 to 1992 in our department. These included 8 from the frontal sinus, 25 from the maxillary sinus, 10 from the ethmoidal sinus, 1 from the maxillary and ethmoidal sinuses, 7 from the frontoethmoidal sinuses and 4 from the sphenoethmoidal sinuses. The patients ranged in age from 8 to 78 years (mean 47.1 years). The ratio of males to females was 31 to 22. The rhinologic symptoms occurred most often in maxillary mucopyoceles and were rare in the other groups whereas ophthalmic symptoms were noticed in most of the cases. All of the cases received surgery and postoperatively most of the initial symptoms subsided except that two patients still had occasional diplopia and one did not recover at all from complete blindness. Two cases had a recurrence and one suffered from subarachnoid hemorrhage shortly after discharge. Surgery is the only treatment modality for mucopyoceles and the building of a new patent communication between the lesion and nasal cavity is important for the success of this surgery.

[Relapsing polychondritis: report of a case and review of the literature].

Relapsing polychondritis (RP) is a rare disease of unknown etiology, characterized by episodic and progressive chondritis, ocular and audiovestibular involvement, and occasional cardiovascular abnormalities. The inflammation typically involves the cartilage of the ears, nose, trachea, larynx, ribs, joints, and Eustachian tubes. The major clinical features include auricular chondritis, arthritis, nasal chondritis, ocular inflammation, chondritis of the respiratory tract, audiovestibular damage, and cardiovascular disorders. RP occurs predominantly in Caucasians and is uncommon in Oriental patients. Two cases of RP have previously been reported in Taiwan. We report one Taiwanese patient who was diagnosed with RP according to the criteria proposed by Damiani and Levine. The patient has bilateral auricular chondritis, episcleritis, and uveitis. Successful treatment was accomplished with systemic corticosteroid and topical corticosteroid eye drops. At an outpatient visit one year and ten months after discharge, there was no evidence of recurrence.

The effects on basal anterior pituitary hormone concentrations by cranial irradiation in patients with nasopharyngeal carcinoma.

Hypopituitarism occurring in patients who received external cranial radiation therapy (RT) have been increasingly recognized. Fourteen healthy patients were collected as control Group I, and 25 patients with nasopharyngeal carcinoma (NPC) were enrolled as Group II. Another 18 NPC patients were enrolled as Group III. Blood was sampled from Group I, Group IIB (before RT), Group IIA (one week after RT) and Group IIIA (1 to 1.5 years after RT). The basal samples were taken for growth hormone (GH), adrenocorticotropic hormone (ACTH), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4). The results showed the T3 level was statistically low in Group IIB compared with Group I. The serum GH and FSH (male only) levels were higher and with statistical significance in Group IIA compared Group IIB. Both GH and ACTH levels decreased and PRL increased with statistical significance in Group IIIA compared with Group IIA. The ACTH decreased with statistical significance in Group IIIA compared with Group IIB. Clinical damage to the pituitary is usually manifested months to years after RT. Therefore, a careful exclusion of these glands from radiation treatment fields is recommended whenever possible.