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Objectives/HypothesisThe p53 tumor suppressor gene plays an important role for cell cycle regulation and is the most frequent mutated gene in head and neck cancer. Controversy remains regarding the biological and clinical value of immunohistochemical identification of the proteins accumulated in association with inactivation of the p53 gene and increased tumor growth. Therefore, the objective of the present study was to perform a cell kinetic analysis of cases with untreated squamous cell carcinoma and to compare the result with immunostaining for p53‐related proteins in the tumor cells.

Verrucous squamous cell carcinoma is a rare type of well-differentiated squamous cell carcinoma with a characteristic morphologic appearance and specific clinical behavior. It has been claimed that this tumor may undergo dedifferentiation after radiotherapy; this will result in a more aggressive behavior. From 1968 to 1980, we have diagnosed and treated 569 squamous cell carcinomas of the larynx. Fourteen of them were reported to exhibit verrucous features macroscopically. These tumors were histopathologically reexamined. All 569 cases were stratified with regard to tumor stage (≤T2 N0 M0) and treatment (irradiation). Six patients of 340 were then diagnosed as having verrucous squamous cell carcinomas, according to the Ackerman criteria. The patients were followed for at least 5 years and regional metastases of poorly differentiated carcinoma developed in at least two patients in the verrucous carcinoma group within 2 1/2 years after full-dose irradiation. Among the patients with nonverrucous carcinoma, this frequency was estimated to be 3%. This study provides evidence that metastatic spread that occurs after irradiation is approximately 10 times more frequent (p< 0.05) for T1–2 laryngeal verrucous carcinomas, as compared to the common type of squamous cell carcinoma.

• We have studied the prevalence of mental disorder in a variety of patients with head and neck cancer in different stages of disease and treatment. Altogether, 59 patients were studied according to a comprehensive psychopathologic rating score and nutritional status. Six patients refused to answer the comprehensive psychopathologic rating score questionnaire. Of the remaining 53 patients, 13 patients were classified as mentally disordered. Five patients were classified as mentally depressed according to a specific comprehensive psychopathologic rating scale depression score. We found that depression was significantly linked to malnutrition. In total, 30% of our patients with cancer with weight loss demonstrated features that were consonant with depression. This suggests that mental depression is associated with physical impoverishment rather than with the malignant condition per se.(Arch Otolaryngol Head Neck Surg 1988;114:1449-1453)

Forty-two patients with malignancies localized to the base of the tongue were treated at Sahlgrenska Hospital between 1971 and 1980. These patients were re-analyzed with respect to symptomatology and clinical outcome. Pain in the mouth, throat, and ears as well as swallowing difficulties were the most frequent overt symptoms of disease. In general, patients experienced symptoms for at least 3 months before a positive tumor diagnosis was made. In all, 75% of the patients were found to have large tumors which extended beyond the base of the tongue. Most of the patients were treated with irradiation. The overall 3-year survival rate was 28%, while individual patient survival was related to the size of the primary tumor and to the occurrence of lymph node metastases. Careful attention to symptomatology may reduce delays in establishing an accurate diagnosis and consequently improve the prognosis for patients with these cancers.

In a randomized trial, 55 patients with acute external otitis were treated with either topical framycitin/gramicidin (Sofradex) or oxytetracycline/hydrocortisone (Terracortril) with polymyxin B (TPB) ear-drops for 1 week. Staphylococcus aureus and Pseudomonas pyocyanea were the bacteria most frequently found in the ear canal; 78% of the patients were cured. However, no significant differences in therapy were found when either of the preparations was used. S. aureus seemed to be most resistant to treatment, while P. pyocyanea was less of a therapeutic problem. Additionally, previous episodes of external otitis or other skin diseases did not seem to influence any treatment given.

To evaluate the hypothesis of CNS involvement in Bell's palsy, the auditory brain stem responses (ABR) of 31 patients were studied. In nine of these patients ABR abnormalities were found. None of these patients showed evidence of dysfunction of the cochlear nerve. Six of the patients who had abnormal ABR were retested after they recovered from the facial paresis. Five of these patients showed persistent ABR abnormality, and one showed a normalization of the ABR. These results may be consistent with an injury at the brain stem level in some patients with Bell's palsy. The possible causative agent of a reactivation of a herpes simplex virus infection is discussed.

OBJECTIVE: To evaluate the possible causal role of pathologic hemostatic mechanisms in sudden hearing loss. DESIGN: The study was prospective. SETTING: The patients were hospitalized, and all tests were performed at the hospital. PATIENTS: Thirty-two consecutive patients with sudden hearing loss participated, as well as a control group of 28 healthy individuals. The control group was matched with regard to body mass index. MAIN OUTCOME MEASURES: Venous blood analyses were made regarding general blood parameters, as well as specific hemostatic parameters. RESULTS: Twenty-five of the patients had some kind of aberration of specific hemostasis parameters; seven patients had an increase in the activity of the plasminogen activator inhibitor 1 (ie, a glycoprotein associated with diminished fibrinolysis) compared with that in the control group (P&lt;.05). Increased plasminogen activator inhibitor levels were most frequently observed among the patients who were overweight. Seven of the oldest patients had an increase of D-dimers, ie, a degradation product of fibrin, and most of these patients had a history of cardiovascular disease. CONCLUSION: Although isolated aberrations in the hemostatic pathway were observed, we concluded that pathologic hemostasis does not seem to have a decisive importance for the pathogenesis of sudden deafness.(Arch Otolaryngol Head Neck Surg. 1994;120:536-540)

• Using light microscopy, we studied the morphologic events of cholesteatoma progression 8 months after ligation of the ear canal in 14 Mongolian gerbils. Although we observed a wide range of progression, four stages of morphologic development could be clearly distinguished among the 28 specimens: stage I, an orthokeratotic plug in the ear canal without tympanic membrane involvement; stage II, partial retraction of the tympanic membrane; stage III, the interface between cholesteatoma encapsulated within the tympanic membrane and mucosal membranes covering the promontorial wall of the middle-ear cavity was characterized by a buildup of granulation tissue with prominent macrophage infiltration; and stage IV, bone destruction. Chronic inflammation was observed in some but not all stage II to IV cases. Our results indicate that hyperkeratosis is a primary event in cholesteatoma development, that the development of the granulation tissue with activated macrophages may be responsible for the bone destruction, and that acute or chronic inflammation is not a prerequisite for the development of cholesteatoma or the bone resorptive process.(Arch Otolaryngol Head Neck Surg. 1993;119:272-275)

• There is evidence that selenium and zinc are involved in malignant neoplasia. The exact role of these trace elements, however, is not completely understood. For this reason, we studied circulating levels of selenium and zinc in relation to food intake and nutritional status in 14 patients with head and neck cancer. Six patients without cancer served as controls. The patients with cancer were in different stages of disease. They were untreated or in an initial phase of oncologic treatment. Five of these patients were severely cachectic according to weight loss and nutritional status, which included body mass index, anthropometric values, and serum albumin level. These patients also demonstrated decreased circulating levels of selenium and zinc. Plasma glutathione peroxidase (selenium-dependent enzyme) activity, however, was not significantly different when the cachectic patients with cancer were compared with controls. We found that the plasma selenium level was positively correlated to both short-term and long-term selenium intake when all 20 patients were accounted for. However, no significant correlation could be shown between plasma selenium and serum albumin levels. Although only one patient demonstrated a plasma value below the reference value, serum zinc was positively correlated to the serum albumin level. We conclude that plasma selenium concentrations are essentially related to food intake but not necessarily to weight loss. Low circulating levels of zinc are, rather, associated with the catabolic state of the patient with cancer.(Arch Otolaryngol Head Neck Surg. 1989;115:1079-1082)

The quality of life (QL) of cancer patients has attracted an increasing interest in recent years. Patients with head and neck cancer often have troublesome symptoms due to the disease and to treatment side effects, which will have an impact on the patient's QL. The aim of this study was to evaluate the possibility of studying QL in relation to well-known clinical parameters. Patient's QL was evaluated according to the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) combined with a diagnosis-specific questionnaire. Quality of life was measured in a cross section of head and neck cancer patients (n = 48) and related to nutritional status, energy intake, severity of disease, and 2-year survival. Fifty-one percent of the patients (mean age, 67 years) fulfilled the criteria proposed for malnutrition, and 55% had a negative energy balance. We did not find any correlation between the severity of the cancer disease and the patient's self-rated QL. However, we found significantly better QL ratings among the 2-year survivors (mean, 63; range 52–76 versus mean, 42; range, 31–54; p &lt; .05). There were few correlations between the QL items and malnutrition. Quality of life measurements offer objective information on well-being, sometimes quite opposite that of other clinical parameters, such as tumor stage. Furthermore, QL measurements may be of prognostic value concerning the survival of head and neck cancer patients. © 1998 John Wiley & Sons, Inc. Head Neck20: 540–548, 1998.

• Twenty-eight consecutive patients with acute unilateral facial palsy were examined with special reference to clinical signs of central nervous system involvement. The clinical investigation in the acute stage of the disease showed that only seven patients had solitary facial nerve dysfunction, while the remaining patients had evidence of more widespread disease involvement. The most frequent finding was a trigeminal dysfunction of the paretic side, as shown by paresthesia and sensibility disturbance corresponding to the sensoritrigeminal area, as well as a dysfunction of the trigeminal component of the corneal reflex of the paretic side. Three patients showed migrating symptoms that were suggestive of a brain-stem disorder. In addition, four patients had an optic neuropathy, while an abnormal brain-stem audiometry response was demonstrated in five patients. The outcome of acute facial palsy one to two years after onset, however, could not be predicted from the clinical central nervous system signs. The degree of the palsy in the acute stage of the disease still seemed to be one of the most important prognostic factors. It is concluded that acute facial palsy is not a single entity, but rather a feature of different neurologic conditions.(Arch Otolaryngol Head Neck Surg 1987;113:516-520)

Verrucous squamous cell carcinoma is a rare type of well-differentiated squamous cell carcinoma with a characteristic morphologic appearance and specific clinical behavior. It has been claimed that this tumor may undergo dedifferentiation after radiotherapy; this will result in a more aggressive behavior. From 1968 to 1980, we have diagnosed and treated 569 squamous cell carcinomas of the larynx. Fourteen of them were reported to exhibit verrucous features macroscopically. These tumors were histopathologically reexamined. All 569 cases were stratified with regard to tumor stage (=T2 N0 M0) and treatment (irradiation). Six patients of 340 were then diagnosed as having verrucous squamous cell carcinomas, according to the Ackerman criteria. The patients were followed for at least 5 years and regional metastases of poorly differentiated carcinoma developed in at least two patients in the verrucous carcinoma group within 2 1/2 years after full-dose irradiation. Among the patients with nonverrucous carcinoma, this frequency was estimated to be 3%. This study provides evidence that metastatic spread that occurs after irradiation is approximately 10 times more frequent (p< 0.05) for T1–2 laryngeal verrucous carcinomas, as compared to the common type of squamous cell carcinoma.

Objectives: To attempt early diagnosis of patients with Bell's palsy by detection of herpesviral DNA in body fluids, and to investigate whether tumor necrosis factor‐α (TNF‐α), a cytokine associated with demyelination, is involved in the inflammatory response in this disease. Study Design: Eleven patients with acute facial palsy admitted within 1 week after onset of the disease were followed in a consecutive prospective study. Methods: Antibodies reactive to herpesviruses were determined by enzyme‐linked immunosorbent assay in serum samples from acute and convalescent (> 2‐week interval) cases. Intrathecal antibody response was investigated by immunoblotting. Polymerase chain reaction amplification of herpesviral DNA was attempted from samples of serum, cerebrospinal fluid, tear fluid, and saliva. TNF‐α and its soluble receptors (types I and II) were assessed in serum and cerebrospinal fluid samples. Results: Ten of the 11 patients demonstrated serologic evidence of herpesviral primary infection or reactivation, supporting the evidence that herpesviruses are the most prevalent etiologic agents in Bell's palsy. Despite this, DNA amplifications by polymerase chain reaction were negative for herpesviruses in the body fluids tested. TNF‐α concentrations were significantly elevated in serum, as compared with controls. Only one patient had a remaining facial nerve dysfunction at follow‐up after 3 months. Conclusion: The absence of herpes DNA in body fluids in the acute stage of serologically confirmed Bell's palsy suggests that viral replication is transient in cases with an early restoration of the facial nerve function. The elevated serum levels of TNF‐α indicate that this cytokine might be a pathogenetic factor related to the demyelination in this disease.

To evaluate the hypothesis of CNS involvement in Bell's palsy, the auditory brain stem responses (ABR) of 31 patients were studied. In nine of these patients ABR abnormalities were found. None of these patients showed evidence of dysfunction of the cochlear nerve. Six of the patients who had abnormal ABR were retested after they recovered from the facial paresis. Five of these patients showed persistent ABR abnormality, and one showed a normalization of the ABR. These results may be consistent with an injury at the brain stem level in some patients with Bell's palsy. The possible causative agent of a reactivation of a herpes simplex virus infection is discussed.

Spontaneous and experimentally induced cholesteatoma in the Mongolian gerbil has been found to exhibit histopathological similarities to human aural cholesteatoma and has been suggested as an experimental model for studies of the clinical situation. In an attempt to further characterize this model, we compared experimentally induced cholesteatomas in the external auditory canal from gerbils with those of the human ear by means of a correlated histopathologic and enzyme histochemical study. The human and gerbilline cholesteatomas revealed similar histopathologic features. Even enzyme histochemically, the human and experimentally induced cholesteatomas demonstrated similar features. Thus glucose-6-phosphate dehydrogenase activity, an indicator of oxidative metabolism, was demonstrated especially in the stratum granulosum cells of the heavily orthokeratinizing squamous epithelium adjacent to the cholesteatomas. The human ear canal skin also revealed enzyme histochemical characteristics similar to the squamous epithelium lining the human cholesteatoma. The hydrolytic enzyme activity (leucyl-aminopeptidase) was strong in the connective tissue surrounding human cholesteatoma when compared with that of ear canal skin. In the gerbilline cholesteatoma, this activity was demonstrated especially in the connective tissue adjacent to eroded bone, which possibly may facilitate cholesteatoma progression. We conclude that experimentally induced cholesteatoma has both histophatological and enzyme histochemical similarities to human aural cholesteatoma and therefore it is suggested that the gerbilline model may be used for studies on the development of human cholesteatoma. Our results support the view that cholesteatoma may originate from migrated hyperkeratinizing cells from the epidermis of the tympanic membrane or the meatus.

The present morphological study was designed to evaluate the significance of Langerhans cells in the pathogenesis of cholesteatoma. Biopsies of middle ear cholesteatomas were examined for Langerhans' cells expressing HLA-DR and anti-Leu 6 antigens by immuno-histochemistry using monoclonal antibodies. No apparent difference in number of cells was observed when epithelium of cholesteatoma was compared with epithelium of healthy ear canals. Expression of HLA-DR antigens was detected on keratinocytes in Aspergillus flavus infected epidermis, used as a control tissue. This finding indicated an increased immunosurveillance of this tissue. However, no such expression of HLA-DR antigens was detected on epidermal cells of cholesteatomas. The results of the present study did not support the hypothesis of Langerhans' cells as having a primary role in the development of cholesteatoma.

• The possible association of some viral infections with the onset of Bell's palsy was examined in a study of 142 patients. The number of probable recent viral infections, as judged by increase in antibody titers or presence of IgM antibodies, did not differ statistically from that found in a sex- and age-matched control group. However, a higher prevalence of herpes simplex virus (HSV) antibodies was found in the patient group with both a complement-fixation (CF) test and a radioimmunoassay (RIA). Moreover, titers of HSV CF antibodies and antibodies against HSV envelope antigens (RIA) were higher in the patient group. The possibility of reactivated HSV infection and transient demyelination of the facial nerve being causatively associated with Bell's palsy is discussed.(Arch Otolaryngol 107:79-81, 1981)

• The present study evaluates the energy and skeletal muscle metabolism in malnourished patients, with and without cancer, in response to nutrition. The energy balance was positive in all patients receiving nutritional support. This led to an increase in body weight and body potassium levels. Glucose turnover increased in all patients. In patients with cancer, elevated glucose turnover reflected increased utilization of glucose preferentially for synthetic pathways rather than for oxidation. Protein synthesis and RNA content in skeletal muscles increased during nutrition. Nutritional support improved energy balance and protein synthesis capacity in skeletal muscles in patients with cancer to the same extent as in malnourished patients without cancer. Malignant cachexia seems to be a consequence of a relative lack of energy and not of impaired energy utilization in host tissues, at least early in the disease.(Arch Otolaryngol 1982;108:697-699)

• A case of mucosal melanoma involved the bronchus, maxillary sinus, and small intestine. Treatment with a combination of autologous tumor cells, BCG vaccine, and cytarabine was given, and the immunological system was investigated regularly. After each treatment episode, there was a transient improvement of the cell-mediated immunity to melanoma antigens. The cutaneous delayed hypersensitivity reaction to PPD was converted to a permanently positive one. In the final stage of the disease, the number of T cells was decreased. Difficulty occurred in interpreting the immunological findings according to the clinical condition.(Arch Otolaryngol 105:48-50, 1979)

• The influence of a paper prosthesis on healing in acute traumatic tympanic membrane perforations was studied in 60 patients randomly selected for a treatment group or a control group. The majority (42 [70%]) were seen within two days. All patients were treated with oral antibiotics for ten days. The overall healing rate two months after the trauma was 94% (37 of 39 patients). No significant difference between the study group and the control patients was observed. Intermittent secretion was seen in six patients but did not influence the outcome. The perforations occurred in patients with normally sized mastoid air cell systems as seen on roentgenograms. We conclude that acute traumatic tympanic membrane perforations do not need to be treated routinely with paper patching.(Arch Otolaryngol Head Neck Surg 1987;113:1285-1287)

In Reply.—We regret that our article, which was a summary of recent and unpublished work from our laboratory, did not give the complete information under the "Patients" section that our control group was matched according to physical activity, age, and malnutrition. Therefore, we hereby want to add the information that our patients with and without cancer had lost similar amounts of weight and that the groups had a comparable degree of malnutrition assessed by conventional means, eg, body weight, actual to ideal weight, triceps skinfold, midarm circumference, serum albumin concentration, and total body potassium. However, it may well be that the patients with cancer were slightly more protein malnourished and their conditions were evaluated from lower serum albumin concentrations. The patients with cancer who received enteral nutrition were also essentially comparable with the patients with cancer receiving parenteral nutrition. However, the groups were too small to allow meaningful comparison between the