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.

Botulinum toxin therapy: functional silencing of salivary disorders.

Botulinum toxin (BTX) is a neurotoxic protein produced by Clostridium botulinum, an anaerobic bacterium. BTX therapy is a safe and effective treatment when used for functional silencing of the salivary glands in disorders such as sialoceles and salivary fistulae that may have a post-traumatic or post-operative origin. BTX injections can be considered in sialoceles and salivary fistulae after the failure of or together with conservative treatments (e.g. antibiotics, pressure dressings, or serial aspirations). BTX treatment has a promising role in chronic sialadenitis. BTX therapy is highly successful in the treatment of gustatory sweating (Frey's syndrome), and could be considered the gold standard treatment for this neurological disorder.

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.

Sudden hearing loss followed by deep vein thrombosis and pulmonary embolism in a patient with factor V Leiden mutation.

OBJECTIVE: Factor V Leiden (FVL) is by far the most prevalent inherited thrombophilic abnormality in Western countries, and this genetic condition has been associated with sudden sensorineural hearing loss (SSHL). Audiologists should be aware that SSHL may be the precursor of life-threatening thromboembolic events, especially in Caucasians who are more likely to be FVL carriers. DESIGN: Case report. STUDY SAMPLE: A 41-year-old male patient. RESULTS: Although this is not the first report of SSHL in a FVL carrier, it is the first to describe SSHL occurring in a heterozygous FVL carrier who--within a month--was also diagnosed with deep vein thrombosis of the left common femoral, saphenous, and popliteal veins, and pulmonary embolism of the left pulmonary artery branch serving the posterior basal segment of the inferior lobe. CONCLUSIONS: SSHL is an emergency condition that warrants prompt medical examination and treatment. Hematological investigations should be considered in SSHL patients at least for those with a family history of thrombotic events, and for women on estrogen-progestin therapy or during pregnancy, with a view to providing adequate antithrombotic prophylaxis and reducing the risk of other thromboembolic events.

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.

Nasal dysfunction induced by chlorinate water in competitive swimmers.

AIMS: Swimmers commonly complain of nasal symptoms probably due to mucosal irritation caused by chlorinated water. The aim of the present prospective study was to investigate changes in nasal function and cytology in a cohort of 15 volunteer competitive swimmers, as compared with a control group of 15 competitive athletes practicing other sports. METHODS: Olfactory threshold for n-butanol was measured in a population of competitive swimmers. Changes in nasal function and cytology were compared between the two groups of volunteer competitive athletes. RESULTS: There were no significant differences between the two groups in terms of mean 20-Item Sino-Nasal Outcome Test scores, peak nasal inspiratory flow, pulmonary peak expiratory flow, or total nasal resistance on anterior active rhinomanometry. Nasal mucociliary transport time (MCTt) was significantly shorter for the non-swimmers than for the swimmers. The mean olfactory threshold for n-butanol in the swimmers was significantly lower than in the other group of athletes. CONCLUSIONS: Data seem to confirm the utility of MCTt in studying nasal mucosa damage caused by chlorinated water. The present results also support the hypothesis of a role for the olfactory threshold in evaluating damage to the olfactory mucosa exposed to chlorinated water.

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.

Nasal functional modifications after physical exercise: olfactory threshold and peak nasal inspiratory flow.

STATEMENT OF PROBLEM: The respiratory nasal effects of physical exercise have been extensively investigated; on the other hand there are no data regarding olfactory threshold modification after aerobic physical exercise. METHODS: The present prospective study investigated the modifications in nasal respiratory flows and olfactory thresholds after controlled aerobic physical exercise in a cohort of 15 adult, healthy volunteers. The Peak Nasal Inspiratory Flow (PNIF), and the Sniffin' Sticks olfactory threshold test were used for our determinations. MAIN RESULTS: The mean PNIF after physical exercise was significantly higher than the mean PNIF value found before physical exercise. Statistical analysis ruled out any significant difference between mean olfactory thresholds pre vs post physical exercise. PRINCIPAL CONCLUSIONS: These outcomes confirmed PNIF sensitivity and reliability also in determining the changes in nasal patency occurring after physical exercise. The active vasoconstriction of nasal mucosa associated with the reduction of blood flow to the olfactory epithelium due to physical exercise may be compensated for by the increase of olfactory molecules that reach the olfactory mucosa because of nasal mucosal shrinkage: this mechanism could explain the stability of mean olfactory threshold after physical exercise.

Anosmia associated with hearing loss and benign positional vertigo after head trauma.

It is well known that head trauma may cause hearing loss, which can be either conductive or sensorineural. Benign paroxysmal positional vertigo and olfactory dysfunction due to head trauma are also well known. The association between sensorineural hearing loss and anosmia, following head trauma, is extremely rare. Two rare cases of post-traumatic occurrence of hearing loss, olfactory dysfunction and benign positional vertigo are reported and the pathophysiology of the association between sensorineural hearing loss, anosmia and benign paroxysmal positional vertigo, after head injury, are briefly discussed. ENT specialists should, in the authors' opinion, be aware of the possible association between anosmia, sensorineural hearing loss and benign paroxysmal positional vertigo after head injury, even in the absence of skull fracture.

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.

Conservative treatment of temporomandibular joint osteoarthrosis: intra-articular injection of sodium hyaluronate.

Promising short-term results in the treatment of temporomandibular joint osteoarthrosis with intra-articular injections of sodium hyaluronate (SH) have been reported in preliminary studies. The present prospective study compared long-term outcomes of temporomandibular joint SH injections with those of a conventional non-surgical treatment (bite-plane). Data from three groups of 20 patients with degenerative temporomandibular joint disease were considered. Group A underwent one cycle of five injections of 1 mL SH. Group B underwent a bite-plane treatment for at least 6 months. We considered a control group of 20 patients who refused any treatments. The description of the outcomes was based on objective and subjective parameters after a 6-month follow-up. Sodium hyaluronate and bite-plane treatments significantly improved patients conditions in all considered parameters. No significant differences in outcomes were confirmed by the statistical analysis. The tolerability of SH treatment resulted to be significantly higher. The analysis of results of serial controls in the SH treated group disclosed a significant worsening in pain at rest by comparing 1 and 6 months follow-up. Sodium hyaluronate infiltration resulted a valid non-surgical treatment for temporomandibular joint degenerative disease. Five well-tolerated intra-articular SH injections achieved equivalent results to those of a 6 months bite-plane treatment. We did not diagnose any complications of SH intra-articular injections. Longer time follow-up is necessary to determine the stability of SH properties.

[Personal experience of adolescents with a brain-injured parent: preliminary study]. / Vécu des adolescents dont l'un des parents est cérébrolésé: étude préliminaire.

OBJECTIVE: To explore the impact of brain injury of a parent on adolescent behavioural and emotional symptoms and personal experience. PATIENTS AND SETTING: Eleven adolescents from 13 to 18 years old with a brain-injured parent with cognitive impairment. MAIN OUTCOME MEASURES: Multiple case report. Assessment of anxiety and depression on the R-CMAS scale and the BDI. Qualitative analysis of a semi-structured interview and of the family drawing. RESULTS: Pathological scores on the R-CMAS scale involved 36% of the cases and the BDI, 45%. Impulsivity involved 36% of cases, difficulties in learning at school 73%, and somatic symptoms 45%. Feeling of loneliness involved 64% of cases and difficulty for the adolescent to speak about feelings in the family 82%. The symbolic position of the brain-injured parent was maintained in all cases. In 45% of cases, the parent was unable to recognize the adolescent, and in 55%, some characteristics of the adolescent were linked to the illness of the parent. A feeling of insecurity pervaded all cases. The family drawing revealed abnormalities in the bodily representation of the family members, especially a lack of hands or a representation of amputated hands in 91% of the cases and unsteadiness of the family members, also represented as ghosts in 82% of cases. CONCLUSION: Living with a brain-injured parent increases depression disorders, a feeling of loneliness and insecurity in adolescents. The inability for the adolescent to recognize parent's personality and the identification with caracteristics of the parent due to the illness is worrying. Abnormalities in the bodily representation of the family members and their unsteadiness are characteristic signs.

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.