Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients.

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients. PATIENTS AND METHODS: The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. RESULTS: Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T(3)/T(4), HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T(3)/T(4) tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome. CONCLUSION: The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.

Interaction between cigarette, alcohol and betel nut use on esophageal cancer risk in Taiwan.

OBJECTIVE: In 2003 esophageal cancer was the sixth leading cause of death among men in Taiwan, but it is the fastest increasing (70%) alimentary tract cancer. The aim of this study was to investigate the impact of different habits of betel nut chewing on esophageal squamous cell carcinoma (SCC) and its interaction with cigarette use and alcohol consumption. MATERIALS AND METHODS: All 165 cases were pathologically proven esophageal SCC patients (all male, mean age = 56.0, range = 35-92 years) diagnosed by biopsy during gastroendoscopic examinations. The control group comprised 255 subjects (all male, mean age = 54.8, range = 40-92 years) selected from patients who had visited the Otolaryngology Outpatient or Inpatient Department of KMUH owing to a benign lesion over this field. All were interviewed to collect demographic and substance use information by a trained interviewer using a standardized questionnaire. RESULTS: Smoking (aOR = 5.4, 95% CI = 2.4-12.9, PAR = 72%), alcoholic beverage drinking (aOR = 17.6, 95% CI = 9.3-35.2, PAR = 76%) and low education level are independent risk factors for esophageal cancer. Although betel nut chewers only had a borderline significant higher risk than nonchewers (aOR = 1.7; 95% CI = 0.8-3.1), those who chewed with a piece of betel inflorescence (aOR = 4.2, 95% CI = 1.4-16.0) and swallow betel-quid juice (aOR = 3.3, 95% CI = 1.3-9.3) had a significant higher risk. Significant dose-response effects were found in daily quantity of drinking and smoking. There is a synergistic effect of these three substances on the development of esophageal cancer. CONCLUSION: Betel nut chewing plays a relevant role in the development of esophageal SCC but adds to the carcinogenetic effect of smoking and alcohol drinking. Direct mucosal contact of betel juice may contribute to its carcinogenesis.

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).

Otogenic brain abscess--a case report.

Brain abscess is one of the life-threatening complications of otitis media. Mortality and morbidity have decreased with the advent of antibiotic therapy. More frequently encountered in cases of acute otitis media in the preantibiotic era, in recent years otogenic brain abscess was noticed almost only in patients of chronic otitis media with cholesteatoma. A case of brain abscess in a 49-year-old female was initially diagnosed as a headache. A high resolution computed tomography (HRCT) scan of the temporal bones later revealed that there were two abscesses over the right side temporal lobe. A modified radical mastoidectomy was performed. Cultures of the middle ear cholesteatoma later grew Pseudomonas aeruginosa and Strenotrophomonas maltophilia. Antibiotic therapy was carried on for three months postoperatively. The patient improved but retained a conductive hearing loss.

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.

Traumatic ossicular chain discontinuity--report of two cases.

In addition to hemotympanum and traumatic eardrum perforation, traumatic ossicular chain discontinuity should also be considered in the differential diagnosis of conductive hearing impairment resulting from head injury. The most common form of these ossicular chain lesions following head injury is incudostapedial joint (I-S joint) separation. We successfully managed two patients with I-S joint separation resulting from head injury through exploratory tympanotomy with ossiculoplasty within the recent 2 years. Both were young females who had sustained head injury resulting from traffic accident with the sequelae of persistent hearing impairment. They both gained significant hearing improvement postoperatively.

Detection of human papilloma virus and Epstein-Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction.

Nasopharyngeal carcinoma (NPC) is an unique epithelial malignancy which occurs at a high frequency in certain regions of Southeast Asia. Human papilloma virus (HPV) and Epstein-Barr virus (EBV) have both been identified in tissue specimens from NPC. Nevertheless, the association between viral infection and NPC remains unclear. The purpose of this study was to demonstrate that simultaneous infection with EBV and HPV can occur in NPC. Eighty-eight fresh tissue samples which contained sufficient and adequate DNA from patients with histologically confirmed NPC were examined for the existence of HPV and EBV DNA by polymerase chain reaction (PCR). The results showed that HPV and EBV DNA were detected in 51% and in 83% of the specimens, respectively. Coexistence of EBV and HPV in NPC was found in 42% of the samples. The "high risk" types including HPV-16 and HPV-18 accounted for 67% of 45 HPV positive samples. Furthermore, 80% of HPV-16 or HPV-18 positive samples also contained EBV DNA. Our findings suggest that coexistence of EBV and "high risk" HPV-16 or HPV-18 infection may be an important factor in the pathogenesis of NPC.

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.

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.

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.

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.

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.

[Congenital nasopharyngeal teratoma: report of a case and review of the literature].

Teratomas are the most common congenital tumors, but teratomas of the nasopharynx are rare and seen almost exclusively in infants, usually in neonates. An unusual case of a neonate with respiratory distress is presented and a nasopharyngeal mass protruding into the oral cavity. After successful removal of the mass, pathological examination revealed a mature teratoma. The management and differential diagnosis are discussed, accompanied by a review of the literature.

The effects of radiation therapy on salivary function in patients with head and neck cancer.

Eighty nasopharyngeal carcinoma (NPC) patients and another eighty head and neck cancer (HNC, non-NPC) patients were enrolled as two experimental groups to study their salivary function by using Tc99m sialography. Twenty healthy subjects were also employed as a control group. The patients received an intravenous injection of 4 mCi of 99mTc-pertechnetate (Tc-99mO4-). The data were collected at a rate of 1 frame per 15 seconds for the total time of 30 minutes, and the patients received stimulations for salivary secretion by ingesting 0.5cc of lemon juice 15 min after the start of data acquisition. The salivary function was measured on Pre-RT (radiation therapy), During-RT and Post-RT periods. The results showed no statistical significance for maximum uptake (%) and excretion rate (%) between Control and Pre-RT group on parotid or submandibular glands function. This was the same in the age groups (age below 40 and age above 40) and sex groups. The NPC group had a decreasing maximum uptake (%) 3 months after RT on both parotid glands and submandibular glands, whereas the HNC group showed no obvious difference. The excretion rate (%) of both parotid and submandibular glands reached its lowest mark after 3-6 months in both the NPC and HNC groups and then started to recover progressively. For NPC patients, the radiation damage to the parotid glands was greater than to the submandibular glands, whereas the effect was reversed on HNC patients. It is important that the radiation therapist should preserve salivary function whenever possible.

The effect of adjuvant chemotherapy for nasopharyngeal carcinoma: a preliminary report.

In the past, radiation therapy was the main treatment modality in nasopharyngeal cancer, but recently, combined induction chemotherapy has become a trend. In this study patients with NPC were divided into two groups. In Group I, 46 cases were treated with chemotherapy (Cisplatin + 5-Fu) and radiation. In Group II, 49 cases were given radiation only. The side effects of chemotherapy were tolerable except for 2 dropouts due to intractable vomiting and semi-coma respectively. Only 17 cases got leukopenia and one case was graded I in BUN evaluation. All of the cases were within normal limits in the platelet and creatinine evaluation. Nine cases acquired hyponatremia. The response rate was 72.7% in the primary site which included 22.7% of the complete response and 50.0% of the partial response with a 80.0% response rate in neck site, which included 56.7% of complete response and 23.3% of partial response. But after the consecutive radiation, the differences of response rate did not show any significance between the two groups. The difference in the response rate between non-keratinizing and undifferentiated carcinoma were significant.