Spiros Manolidis

Malignant mucosal melanoma of the head and neck

Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5‐year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5‐year survival.

Unrecognized benign paroxysmal positional vertigo in elderly patients

Balance disorders in elderly patients are associated with an increased risk of falls but are often difficult to diagnose because of comorbid chronic medical problems. We performed a cross-sectional study to determine the prevalence of unrecognized benign paroxysmal positional vertigo (BPPV) and associated lifestyle sequelae in a public, inner-city geriatric population. Dizziness was found in 61% of patients, whereas balance disorders were found in 77% of patients. Nine percent were found to have unrecognized BPPV. Multivariate analysis demonstrated that the presence of a spinning sensation and the absence of a lightheadedness sensation predicted the presence of unrecognized BPPV. Patients with unrecognized BPPV were more likely to have reduced activities of daily living scores, to have sustained a fall in the previous 3 months, and to have depression. These data indicate that unrecognized BPPV is common within the elderly population and has associated morbidity. Further prospective studies are warranted.

PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma

Purpose: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic α (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC. Experimental Design: More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens. Results: We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A → G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples. Conclusions: These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.

Use of plain radiography and computed tomography to identify fish bone foreign bodies

INTRODUCTION: Fish bones are the most common aerodigestive foreign bodies in adults. Radiographic studies, often ordered for diagnosis, have questionable utility. METHODS: With a laryngoscope, bones from 10 fish species were placed in a variety of positions in a human head and neck cadaver specimen. Plain films and CT scans were obtained and evaluated by blinded readers. RESULTS: Plain radiography exhibited a sensitivity and specificity of 39% and 72%. Cooking did not grossly change radio-opacity. The species of fish affected visibility in soft tissue, without correlation to the characteristic optical density of each species. Bones placed orthogonal to the film in the vallecula were most readily identified. CT scanning correctly identified 9 of 10 bones. CONCLUSIONS: Plain radiography poorly visualizes fish bone foreign bodies in soft tissue; visibility varied with fish species, location, and orientation. CT is the test of choice to radiographically diagnose fish bone impactions. (Otolaryngol Head Neck Surg 2000;123:435-8.)

Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3

Clinical otosclerosis (OMIM 166800/605727) has a prevalence of 0.2-1% among white adults, making it the single most common cause of hearing impairment in this group. It is caused by abnormal bone homeostasis of the otic capsule with the consequent development of sclerotic foci that invade the stapedio-vestibular joint (oval window) interfering with free motion of the stapes. Impaired ossicular chain mobility results in a conductive hearing loss. We identified the first locus for otosclerosis (OTSC1) on chromosome 15 in 1998 and reported a second locus (OTSC2) on chromosome 7 last year. Here we present results of a genome wide linkage study on a large Cypriot family segregating otosclerosis. Results of this study exclude linkage to OTSC1 and OTSC2 and identify a third locus, OTSC3, on chromosome 6p. The defined OTSC3 interval covers the HLA region, consistent with reported associations between HLA-A/HLA-B antigens and otosclerosis.

DNA sequence analysis of GJB2, encoding connexin 26: Observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls†

Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi‐ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC). Sixteen non‐coding sequence variations were also identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13 novel variants. A diagnosis of GJB2‐associated hearing loss was confirmed for 63 cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases carrying novel or unclassified variants (1.8 %) and 18 cases carrying the controversial V37I variant were identified (3%). In addition, 294 control subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence variations in the coding region of GJB2 were identified among controls including 2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1 controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence variations were identified among controls in the non‐coding regions in and around GJB2 exon 2. Of particular interest among controls were the variability in carrier rates and ethnic stratification of alleles, and the complex genotypes among Asians, 47% of whom carried two to four sequence variations in the coding region of GJB2. These data provide new information about carrier rates for GJB2‐based hearing loss in various ethnic groups and contribute to evaluation of the pathogenicity of the controversial V37I variant.

Thyroid Surgery: A Comparison of Outcomes between Experts and Surgeons in Training:

OBJECTIVES: Our objective was to compare the results of thyroid surgery performed by residents in a large metropolitan public hospital (MPH) with those performed by faculty in a large private hospital (PH) setting. METHODS: All records of thyroid surgery performed by otolaryngologists for the period between 1986 and 1998 were reviewed. Inclusion criteria were adequacy of data and follow-up. Ninety-two thyroid procedures performed by residents in an MPH were compared with 181 thyroid operations in a PH setting performed by the faculty of these residents for differences in accuracy of diagnostic studies, operative parameters, and complication rates. RESULTS: The demographic distribution in both groups was similar. Presenting symptoms were twice as frequent in the MPH group (45% vs 22%). More total thyroidectomies were performed in the PH group (49% vs 32%). Blood loss, operative time, and hospitalization days were similar in both groups. Preoperative fine needle aspiration and intraoperative frozen section results showed sensitivities and specificities that were comparable. No permanent vocal cord paralysis was observed in either group. Permanent hypocalcemia was more frequent in the PH group (8.8%:PH vs 5.1%:MPH). CONCLUSIONS: The results of thyroid surgery performed by residents in training in an Otolaryngology-Head & Neck Surgery program in an MPH, measured by rates of complications, length of hospitalization, and duration of surgery, are similar to those of faculty at a PH setting in groups of patients with very similar characteristics.

Diagnosis and management of lateral sinus thrombosis.

Objectives: To define the contemporary management of septic otogenic lateral sinus thrombosis. Study Design: Retrospective case series identified through database search of otologic surgical cases managed by a single surgeon in four teaching hospitals over a 6-year period. Methods: Twelve patients presenting with lateral sinus thrombosis of otogenic cause were the subjects of this study. Patients with incomplete medical records or unknown outcomes were excluded. Results: Lateral sinus thrombosis was the result of chronic otitis media in 50% of cases, with five of these patients having cholesteatoma. In addition, there were seven associated intracranial complications in six patients in this series. All patients underwent medical and surgical treatment. Aggressive and early surgical treatment was tailored to the degree of preoperative and intraoperative findings. The sigmoid sinus was resected in six of the patients with a variable degree of inferior margin proportional to the extent of thrombosis. Thrombectomy alone under vascular control with reestablishment of flow was used to remove the septic thrombus in the other six patients. There were no complications in these patients. Conclusion: Early and aggressive surgical intervention of this otogenic complication can potentially minimize mortality, hospital stay, and length of medical treatment.

Consensus panel on role of potentially ototoxic antibiotics for topical middle ear use: Introduction, methodology, and recommendations.

Abstract A special consensus panel of the American Academy of Otolaryngology-Head and Neck Surgery was appointed by Academy President Dr Jonas Johnson (2003) to determine the appropriate role of potentially ototoxic topical antibiotics in the treatment of ear disease. The consensus panel wished to determine, using current best evidence, if there were differences in efficacy between the potentially ototoxic and the nonototoxic topical antibiotics. This evidence-based review is designed to answer the specific question, ”Are there differences in clinical treatment efficacy between the aminoglycoside based ototopical antibiotic drops and the fluoroquinolone based antibiotic drops?“ A MEDLINE literature review was performed in September 2002. MeSH search terms included ”ototopical antibiotics“ and ”efficacy,“ with limits for human subjects and titles with abstracts. Fifty publications were identified. Four publications were eliminated from the review process because they were not in English (1 each in Japanese, French, Polish, and Hebrew) and 6 others were eliminated because they did not address the question of efficacy. A total of 40 relevant publications were reviewed and graded according to the standards established by the Centre for Evidence-based Medicine. Each article was reviewed and graded independently by 2 reviewers.

The development of antibiotic resistant organisms with the use of ototopical medications

OBJECTIVE: There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic-resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence-based review to answer the following clinical question, “Do antibiotic ototopical medications induce antibiotic resistant organisms?” STUDY DESIGN: We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as “ototopical antibiotics,” “ototopical drops,” “antibiotic resistance,” “topical antibiotics and otitis externa,” “otitis externa and treatment,” “otitis externa and antibiotic drops,” “otitis externa and ototopical drops,” “otitis media,” “otitis media and treatment,” “otitis media and antibiotic drops,” “chronic suppurative otitis media,” “chronic suppurative otitis media and treatment,” “chronic suppurative otitis media and antibiotic drops,” “ otitis externa and resistant organisms,” “otitis media and resistant organisms,” “chronic suppurative otitis media and resistant organisms,” “ophthalmic antibiotic drops,” “draining ear,” “P.E. tube otorrhea,” “pressure equalizing tube otorrhea,” “pressure equalizing tube otorrhea and treatment,” and “pressure equalizing tube otorrhea and ototopical therapy” to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. RESULTS: After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post-tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa. CONCLUSIONS: Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.