How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Influence of number of drugs on olfaction in the elderly.

BACKGROUND: The etiology of age-related olfactory loss is still unclear, but it has been claimed that polypharmacotherapy may contribute to olfactory dysfunction, particularly in the elderly, who are more likely to need multiple drugs. The present pilot study investigated the relationship between smell and the number and type of drugs taken in a group of elderly. METHODOLOGY: 50 elderly volunteers (over 64 years old) who were healthy from the sinonasal standpoint (SNOT-22 under 1) and had no cognitive impairments [Mini Mental State Examination (MMSE over 18) were administered the Screening 12 test and tested on their n-butanol olfactory threshold. Their olfactory performance was then connected with the number and type of drugs participants used. RESULTS: The mean age of the included volunteers was 74 plus/minus 7 years. No association emerged between odor identification and number of drugs taken. The number of drugs taken correlated directly with a worse olfactory threshold and with a worse MMSE score, meaning a worse cognitive status. Odor identification significantly worsened with age. Comparing those volunteers taking only one drug known to not influence olfaction with another sub-group of volunteers taking five or more drugs, it was evident that subjects taking only one drug scored significantly better in olfactory threshold test and MMSE, and marginally better in olfactory identification test. For what concerns the difference between male and female volunteers, no difference in olfactory test result was shown, both for threshold and identification. Univariate analysis showed a direct correlation between the consumption of calcium channel blockers, beta-blockers, acetylsalicylic acid and olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell, and so did potassium-sparing diuretics. Multivariate analysis showed that MMSE scores correlated with a better sense of smell, that is a lower olfactory threshold, and that beta-blockers and acetylsalicylic acid negatively affected olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell. CONCLUSIONS: The number of drugs taken demonstrated to be significantly correlated with a worse olfactory threshold and worse MMSE. Larger studies on elderly volunteers are needed to confirm these preliminary findings.

[Facing a serious disease during adolescence despite a defective parental support: The experience of cancer]. / Faire face à une maladie grave à l'adolescence malgré un étayage parental défaillant : l'exemple du cancer.

Facing a serious somatic disease during adolescence without any parental support is a very difficult life event. In this paper, we discuss the situation of teenagers facing deep emotional deprivation that existed prior to the illness and is reinforced by the lack of parental support during treatment. After analyzing the psychopathological mechanisms involved in such situations - in parents, teenagers, and healthcare teams - we hypothesize that the absence of involvement of parents can sometimes represent, for those who are not able to meet their child's emotional needs, a paradoxical way to take care of him.

Temporal bone carcinoma. Current diagnostic, therapeutic, and prognostic concepts.

Temporal bone carcinoma is an uncommon aggressive malignancy. Its low incidence and the absence of a globally accepted staging system still make it difficult to compare different centers' approaches and results. In this review of the main available studies dealing with temporal bone carcinoma since 1995, we consider its rational preoperative staging and assessment, compare the effectiveness of different treatments by tumor stage, and outline the main actuarial prognostic factors.

The EGFR-mTOR pathway and laryngeal cancer angiogenesis.

Epidermal growth factor receptor (EGFR) is a trans-membrane tyrosine kinase taking part in cell transformation and tumor progression. One of the downstream pathways controlled by EGFR involves the mammalian target of rapamycin (mTOR), a proto-oncogene activated in several cell functions. Recent evidence seems to confirm that both EGFR and mTOR regulate angiogenesis. The aim of this study was to investigate the expression of EGFR and mTOR in laryngeal squamous cell carcinoma (LSCC) cells in a retrospective clinical setting and their correlation with tumor neo-angiogenesis, judged on the grounds of CD105-assessed microvascular density (MVD), and prognosis. We considered 76 consecutive patients with LSCC treated with surgery alone. Immunohistochemical expressions of EGFR, mTOR, and CD105 were measured using image analysis and findings underwent statistical analysis using univariate and multivariate models. We found that nodal status correlated significantly with patient prognosis in terms of disease-free survival (DFS) (p = 0.01). There was a strong direct correlation between mTOR and EGFR expression (p = 0.0003), and between mTOR and CD105-assessed MVD (p = 0.0025). Patients with a CD105-assessed MVD >5.28 % had a significantly higher recurrence rate (RR) (p = 0.026), and a significantly shorter DFS (p = 0.025). On multivariate analysis, only N stage [hazard ratio (HR) 3.54, p = 0.009] and CD105-assessed MVD (HR 2.87, p = 0.027) maintained their independent prognostic significance in terms of DFS. Judging from our promising findings, the EGFR-mTOR pathway should be investigated further to understand its role in LSCC neo-angiogenesis.

Human olfactory sensitivity for bourgeonal and male infertility: a preliminary investigation.

Olfactory receptor (OR) expression is also present in the sperm cells and could mediate sperm chemotaxis. OR1D2 was the first OR expressed in the testis demonstrated to be involved in chemotaxis and to be expressed also in the nose with a similar behavior. Bourgeonal is the OR1D2 most potent known agonist. Infertility affects ~15 % of couples in western countries and sometimes it is unexplained. This pilot study compared the bourgeonal olfactory thresholds, the ability of sperm to sense the bourgeonal and the frequency of 13 single nucleotide polymorphisms (SNPs) of OR1D2 gene in nine males suffering of unexplained infertility with a control group of 15 healthy males. The mean olfactory threshold for bourgeonal was statistically different between the study group (10.5 ± 3.7; median 12.3) and the control group (14.0 ± 2.8; median 15.5) (p = 0.006). Statistical analysis showed a significantly higher percentage of spermatozoa that migrated toward the capillaries filled with bourgeonal in the control group compared to the study group (p < 0.0001). Sperm migration was equally inhibited in both groups of subjects when, together with bourgeonal, capillaries were filled with undecanal, a strong bourgeonal inhibitor (p = 0.42). The 13 SNPs of OR1D2 revealed a statistically significant difference for allele and genotype frequency of rs769423 in study group versus control group (p = 0.02). The present preliminary study seems to confirm the important role of OR1D2 both in nose and spermatozoa and may explain the idiopathic infertility of the study group. Further studies on larger series are mandatory to confirm our preliminary evidence.

Sensorineural hearing loss in ankylosing spondylitis treated with TNF blockers.

OBJECTIVES: Sensorineural hearing loss (SNHL) in the uncommon disease ankylosing spondylitis (AS) has been previously reported. We analysed the relationships between AS, anti-TNF drug treatment, and SNHL. METHODOLOGY: We determined pure tone thresholds in 28 consecutive patients with AS who were treated with the TNFalpha inhibitors etanercept or infliximab, or with a TNFalpha inhibitor plus methotrexate (MTX). RESULTS: SNHL was diagnosed in 16 patients (57.1%): 7/7 (100%) of those treated with anti-TNFalpha plus MTX, and 9/21 (43%) of those treated with anti-TNFalpha alone. We found a significant association between SNHL and treatment modality (p = 0.011) or treatment time in months (p = 0.020). CONCLUSIONS: The SNHL rate was significantly higher in patients treated with anti-TNFalpha plus MTX than those treated with anti-TNFalpha alone. The culpability of anti-TNF therapy was supported by the association between SNHL and treatment time, which was longer for anti-TNFalpha plus MTX than for anti-TNFalpha alone. SNHL may be due not only to AS, but also to drug-induced vasculitis of the labyrinthine artery or its cochlear branch.

The role of survivin expression in the differential diagnosis of laryngeal (glottic) verrucous squamous cell carcinoma.

AIMS: Laryngeal verrucous squamous cell carcinoma (VSCC) is a highly differentiated carcinoma (SCC) whose histological diagnosis has many pitfalls in particular considering small biopsies: multiple glottic biopsies may be necessary to conclude for a malignant or benign lesion (papillary hyperplasia). Survivin is a member of the inhibitor of apoptosis protein family. Survivin over-expression has been demonstrated in laryngeal SCCs. The aims of the present study have been to evaluate for the first time survivin expression in glottic VSCC and investigate the potential role of survivin expression in the differential diagnosis of laryngeal VSCC. METHODS: Survivin expression was determined in 11 consecutive cases of glottic VSCC, in 24 cases of glottic papillary hyperplasia, and in 23 cases of SCC. RESULTS: Nuclear survivin reaction predominated in laryngeal VSCCs, papillary hyperplasias, and SCCs. Mean survivin expressions in the VSCC basal layer, hyper-proliferative areas of laryngeal papillary hyperplasia, and SCC were 62.7%, 68.3%, and 70.0%, respectively. Mean survivin expression was 15.6% in VSCC parakeratosis and 1.5% in papillary hyperplasia parakeratosis (p<0.001). CONCLUSIONS: Survivin expression was significantly higher in parakeratosis areas of laryngeal VSCC than in parakeratosis areas of laryngeal papillary hyperplasia. Immunohistochemical determination of survivin expression in parakeratosis areas may be a promising tool to substantiate differential diagnosis between glottic VSCC and papillary hyperplasia.

CD105-assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma.

AIMS: Angiogenesis is essential for malignancies growth. CD105 is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. The aim of this study has been to determine the expression of CD105 in laryngeal squamous cell carcinoma (SCC) and to investigate the role of CD105-assessed mean vascular density (MVD) in predicting patients' prognosis. METHODS: The sections of 43 consecutive cases of laryngeal SCC were stained with mouse monoclonal antibody CD105. All the measures were performed by a computer-based image analysis system. The percentage of the fields occupied by CD105-assessed micro-vessels was determined. RESULTS: The mean CD105-assessed MVD were 11% and 6% in laryngeal SCC with and without malignancy recurrence, respectively. Multivariate logistic regression stated that CD105-assessed MVD was significantly related to disease recurrence (p=0.030). CONCLUSIONS: Our preliminary results suggest that CD105-assessed MVD may be a valuable parameter for predicting patients having an increased risk of developing laryngeal carcinoma loco-regional recurrence.

[Infected parotid cyst as a cause of facial palsy]. / Infizierte Parotiszyste als Ursache einer Fazialisparese.

BACKGROUND: Inflammatory processes are a rare cause of peripheral facial palsy. In most cases even massive infection does not lead to a loss of facial nerve function. In the literature, only 8 cases of facial paralysis associated with parotid cyst have been described. PATIENT AND RESULTS: We present a case of facial palsy caused by an inflamed cyst of the parotid gland. The patient was operated on with the diagnosis malignant parotid tumor. The pathological report showed a squamous epithelial cyst, massive lymphocytic infiltration. CONCLUSIONS: As a rule the combination parotid gland lesion and facial palsy is a sign of malignancy, clinicians should be aware that, on rare occasions, facial nerve dysfunction may result from benign parotid gland disease.

Nuclear expression of maspin is associated with a lower recurrence rate and a longer disease-free interval after surgery for squamous cell carcinoma of the larynx.

AIMS: Maspin, a protein belonging to the serpin superfamily, is the product of a tumour suppressor gene. Tissue distribution studies have shown maspin expression in normal mammary epithelial cells, in the placenta, prostate, thymus, testis, oral cavity, small intestine, skin, and cornea. Maspin is expressed but down-regulated in human breast, prostatic, and colonic cancers but apparently up-regulated in pancreatic, ovarian, and gastric cancers. Only two studies concerning maspin expression in head and neck carcinomas are available. The present study is the first attempt to determine maspin expression in laryngeal carcinoma. METHODS AND RESULTS: Maspin expression was evaluated in 21 cases of laryngeal carcinoma consecutively treated with an exclusively surgical approach with a follow-up period longer than 24 months. The expression of p53, p27 and MIB-1 was also studied. Two patterns of distribution of maspin in laryngeal neoplastic cells were found. Cytoplasmic expression of maspin was identified in 47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the cases. A statistically significant difference in nuclear maspin expression between the group of patients without carcinoma recurrence and the group with evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis showed a statistically significant direct correlation between nuclear maspin expression and disease-free intervals after surgical treatment calculated in months (P = 0.028). A significant inverse correlation was disclosed between nuclear maspin staining and MIB-1 (P = 0.028). A trend of increasing p27 expression was noted in cases with positive nuclear maspin expression. Nuclear maspin expression was not statistically correlated with p53 expression. A trend towards direct correlation between cytoplasmic maspin expression and squamous cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression did not correlate with p53, MIB-1 or p27 expression. CONCLUSIONS: These preliminary results suggest that nuclear location of maspin is a good prognostic factor in laryngeal carcinoma.

Treatment of complications of parotid gland surgery.

Although several reports in the literature have documented the surgical technique, and the oncological outcome achieved with parotidectomy, only a few articles have described the complications of parotid gland surgery and their management. Several complications have been reported in parotid surgery. We re-classified the complications of parotidectomy in intra-operative and post-operative (early and late). The commonest complications after parotidectomy are temporary or permanent facial palsy and Frey's syndrome.

Facial nerve paralysis secondary to acute otitis media in infants and children.

Nowadays, facial paralysis is an uncommon complication of acute inflammation of the middle ear, with an estimated incidence of 0.005%; it was not so rare in the pre-antibiotic era, occurring in 0.5-0.7% of middle ear inflammatory processes. We would like to highlight this complication of acute otitis media, a common paediatric complaint. We present three new cases of facial palsy in children with acute otitis media and discuss the etiological mechanisms and different approaches to the treatment; a flow chart for facial paralysis in acute otitis media is also presented. Our three patients recovered completely after mastoidectomy (first two cases) and myringotomy with antibiotic therapy (third case). Facial paralysis is an uncommon complication of otitis media which requires appropriate care. Following our experience and revision of literature on the subject, antibiotic therapy and myringotomy are the first-line procedures. Surgery should be employed in case of acute or coalescent mastoiditis, suppurative complications and lack of clinical regression.

Deep neck infection: a present-day complication. A retrospective review of 83 cases (1998-2001).

Deep neck infections are less and less frequent today than in the past. Nevertheless, their complications are often life-threatening. The present study reviews the experience of the Department of Otolaryngology and Head and Neck Surgery of Padua with deep neck infections during the period from 1998 to 2001. Eighty-three patients (55 males and 28 females) were retrospectively considered. The site of origin of deep neck infection was identified in 76 patients (91%). The most common cause was dental infection, occurring in 35 cases (42%). In 12 cases (14%) deep neck infection was a complication of oropharyngeal infection. The relatively high incidence of Peptostreptococcus sp, Streptococcus viridans, Streptococcus intermedius and constellatus isolation was consistent with the high rate of odontogenic cases. Surgery was advocated as the treatment for any infection of the deep neck spaces. The recent series has demonstrated that medical treatment did not seem to increase complication rates or mortality. Our tailored approach (medical or medical and surgical) based on clinical and radiological evidence was successful in 97% of the patients.

Langerhans' cell histiocytosis: temporal bone involvement.

In Langerhans' cell histiocytosis, radiological findings on temporal bone involvement show destructive bone lesions involving the mastoid, with the squamous part and middle ear less affected. Computed tomography (CT) is the preferred imaging modality for describing the extent of temporal bone involvement. CT also has an important role in monitoring disease activity and response to treatment. Bone scintigraphy seems to be less sensitive than radiography in detection of these lesions.

Hearing results of ossiculoplasty in Austin-Kartush group A patients.

OBJECTIVE: To compare hearing results in patients who underwent ossiculoplasty for Austin-Kartush group A impairments (incus erosion, malleus handle present, stapes superstructure present) with the results in patients with an intact ossicular chain who required only myringoplasty. The literature on hearing results of ossiculoplasty with different types of prostheses and different techniques is reviewed. PATIENTS AND STUDY DESIGN: This study retrospectively reviews a series of 181 consecutive ossiculoplasties and 204 consecutive myringoplasties. SETTING: The study was carried out partly at a private practice and partly in an academic tertiary referral center. MAIN OUTCOME MEASURES: This study complies with levels 1 and 2 of the guidelines recommended by the American Academy of Otolaryngology--Head and Neck Surgery (1995). RESULTS: When success was defined as a postoperative air-bone gap within 10 dB, the success rate was higher for myringoplasty (81%) than for ossiculoplasty (55%). When success was defined as a postoperative air-bone gap within 20 dB, the success rate was 97% in myringoplasties and 85% in ossiculoplasties. There was no significant deterioration over time of the mean postoperative air-bone gap for any frequency. CONCLUSION: Cumulative data from several authors show that -50% of patients undergoing partial ossiculoplasty have a postoperative air-bone gap of 0 to 10 dB, and 80% have a postoperative air-bone gap of 0 to 20 dB. Equally good results may be achieved with autograft (no difference was found between interposition of the incus or the head of the malleus), homograft, or alloplastic partial prostheses. With alloplastic total prostheses, 36% of patients have a postoperative air-bone gap of 0 to 10 dB, and 74% have a postoperative air-bone gap of 0 to 20 dB.

Laryngeal leiomyosarcoma.

We report one case of leiomyosarcoma (LMS) of the larynx occurring in a patient with a history of immunosuppressive therapy, and offer a critical review of the literature. Epstein-Barr virus (EBV) genome was not identified in the neoplastic cells. The patient was treated with endoscopic resection and post-operative radiotherapy. Lung metastasis and thyroid infiltration became evident 14 months following treatment despite the absence of laryngeal recurrence. Progressive decline occurred and the patient died 15 months after diagnosis.

Functional MR with use of FLASH sequences in the evaluation of the phono-articulatory tract.

The aims of this study are to determine visualization of normal phonation structures with the use of MR fast sequences and anatomical reference indices which can be used in evaluating upper resonator pathologies. A total of 12 normal subjects were studied, a 1 T system, a volumetric receiving head and neck coil and FLASH sequences for one sagittal and two coronal scans. Each subject was instructed to take a deep breath and then to produce the vowel sounds for the entire duration of the scan. The movement of the following anatomical structures were considered: lips, tongue, soft palate, pharynx and epiglottis. For each subject sagittal scans were used to measure the minimal palate tongue distance (p-t), the minimal anterio-posterior diameter of the mesopharynx (mp), and the epiglottis excursion angle (ep) with respect to the plane determined by the false vocal cords. Our results were compared with a diagrammed representation of tongue movements (vocal trapezium). This study underlines the validity of MR imaging techniques in the study of the phono-articulatory tract, because MR provided good detail of the phono-articulatory structures enabling an overall functional evaluation. MR would appear useful in evaluating defects in the velum and palate, in staging of oropharyngeal neoplasms and in surgical reconstructions of the tongue.