Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy.

This study was undertaken to evaluate the association between demographics, lifestyle habits, and clinical data and overall survival (OS), recurrence and second primary cancer (SPC) in patients with first primary head and neck cancer (HNC). We retrospectively reviewed data from 482 patients treated at the "Agostino Gemelli" Teaching Hospital, Rome, between 2002-2012 for primary HNC. Individual parameters were evaluated for association with specific outcomes such as OS, cancer recurrence and second primary cancer (SPC) appearance using hazard ratios (HR) and 95% confidence intervals (CIs). Five-year OS was 60.6% for all HNC cases, 49.0% for oral cavity, 54.8% for oropharynx, 50.0% for hypopharynx and 63.4% for larynx. Predictors of OS were older age (HR = 1.04; 95% CI: 1.02-1.05) and advanced tumour stage (HR = 2.00; 95% CI: 1.41-2.84). The risk of recurrence was associated with drinking 8-14 drinks per week (HR = 1.73; 95% CI: 1.00-2.97). The risk of developing SPC increased with advanced tumour stage (HR = 2.75; 95% CI: 1.39-5.44) and with smoking for more than 40 years (HR = 3.68; 95% CI: 1.10-12.30). OS differed among HNC sites. Increasing age was an unfavourable predictor of HNC OS. Tumour stage was a prognostic factor both for OS and for risk of developing SPC. Alcohol and tobacco consumption were prognostic factors for recurrence and SPC, respectively.

Sudden cochlear hearing loss as presenting symptom of arachnoid cyst of the posterior fossa.

Arachnoid cysts account for almost 1% of neoformations located in the cerebellopontine angle. The aetiopathogenesis is unknown. Arachnoid cysts of the cranial posterior fossa may produce symptoms typical of a tumour such as headache, dizziness, tinnitus and progressive sensorineural hearing loss. Management of these lesions is still controversial; if the arachnoid cyst is symptomatic, surgical treatment is usually recommended. The case is described of an adult female with sudden unilateral cochlear hearing loss as presenting symptom of an arachnoid cyst in the cranial posterior fossa.

Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications.

The cyclin D1 (CCND1) gene is amplified, rearranged, and overexpressed frequently in human cancer, including squamous cell carcinoma. The gene dosage of CCND1 was examined in 51 primary laryngeal squamous cell carcinomas, and amplification of the gene was found in 9 (17.6%) cases. CCND1 amplification did not correlate with age, tumor localization and extension, cervical lymph node involvement, histopathological grading, and epidermal growth factor receptor levels. In a univariate analysis, CCND1 amplification, tumor extension, lymph node involvement, poor histological differentiation, and high epidermal growth factor receptor levels were correlated significantly with shorter overall survival. In a median follow-up period of 29 months, the overall survival rate was 71.4% for patients affected with tumors displaying a normal CCND1 dosage and only 25.0% for patients affected with tumors carrying amplified CCND1 (P = 0.0288). In a multivariate analysis, only CCND1 and tumor extension retained statistically significant prognostic values (P = 0.037 and 0.041, respectively). This is the first report in which CCND1 amplification is identified as a significant independent prognostic factor in laryngeal carcinoma. Evaluation of CCND1 amplification could be applicable to the clinical management of laryngeal cancer, allowing identification of patients with poor prognoses.

Human papillomavirus infection and epidermal growth factor receptor expression in primary laryngeal squamous cell carcinoma.

PURPOSE: This study was designed to add new data about laryngeal carcinogenesis, a multistep process in which chemical and/or viral agents induce and promote successive alterations in growth factor-linked signal transmission pathways, genetic instability, and mutations in key genes involved in cell growth control. Epidemiological evidence suggests that human papillomavirus (HPV) infection may be associated with the development of laryngeal cancer. EXPERIMENTAL DESIGN: In this report, we have analyzed the prevalence of HPV infection and epidermal growth factor receptor (EGFR) expression in a series of 42 laryngeal squamous cell carcinomas by PCR with HPV consensus primers and by a radioligand receptor assay, respectively. RESULTS: HPV DNA was detected in 15 of 42 (35.7%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33 genotypes. At analysis by Mann-Whitney nonparametric statistical test, EGFR level was found to be significantly higher in HPV-infected than in HPV-negative cases (T = 440; P = 0.002). EGFR overexpression (EGFR-positive status >6 fmol/mg protein, the arbitrary cutoff value chosen) was found in 20 of 42 (47.6%) tumors, and it was associated with HPV infection in a statistically significant extent (chi(2) = 4.686; P = 0.03). CONCLUSIONS: Viral oncoproteins have been shown to induce a perturbation of the cell response to signals for growth and differentiation; these findings confirm that enhanced EGFR expression and activation in laryngeal squamous cell carcinoma may occur also as a consequence of HPV infection and support the hypothesis of an involvement of HPV infection in laryngeal carcinogenesis.

Telomerase activity in human laryngeal squamous cell carcinomas.

The activation of telomerase has been shown to be an important step during tumorigenesis in a variety of malignancies and is associated with characteristics of cellular immortality, such as indefinite proliferative potential. We studied telomerase activity in a series of human laryngeal carcinomas. Thirty-six tumors from 35 patients were studied using a sensitive PCR-based technique, the telomeric repeat amplification protocol assay. Telomerase activity was present in 32 tumors (89%), and the level of activity correlated with the stage of disease. In two of four telomerase-negative tumors, we found evidence of an inhibitor of telomerase activity. In many cases, samples of mucosa surrounding the tumor were also studied, and telomerase could be detected in 16 of 21 patients. For this reason, we proceeded to perform a topographical analysis that demonstrated a pattern of telomerase activity suggestive of a spread of telomerase-positive cells. In conclusion, these data indicate that telomerase activation is important for laryngeal carcinogenesis and that telomerase assay might be a valuable addition to determine the spread of the disease.

Association between cyclin D1 (CCND1) gene amplification and human papillomavirus infection in human laryngeal squamous cell carcinoma.

Head and neck squamous cell carcinomas (SCCs) seem to follow a multistep process of carcinogenesis in which chemical and/or viral agents are associated with specific genetic alterations. The prevalence of human papillomavirus (HPV) infection and the amplification of the cyclin D1 (CCND1) gene were evaluated in a series of 75 laryngeal SCCs by PCR with HPV consensus primers and Southern blot analysis with a CCND1-specific probe, respectively. HPV DNA was detected in 22 of 75 (29.3%) tumors, and it belonged almost exclusively to the highly oncogenic HPV-16, HPV-18, and HPV-33. CCND1 gene amplification was found in 15 of 75 (20%) tumors, and it was associated with HPV infection in a statistically significant manner (chi2 = 20.3; P < 0.001). Because the viral oncoproteins E6 and E7 from high-risk HPV types are known to promote genomic rearrangements, these findings suggest that amplification of the CCND1 gene in laryngeal SCCs may occur as a consequence of the genomic instability associated with HPV infection. In turn, amplified CCND1, either alone or in conjunction with a direct action of the viral oncoproteins E6 and E7, could lead to a perturbation of the cell cycle. This model could explain the involvement of high-risk HPV types in laryngeal carcinogenesis.

Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction.

Although human papillomaviruses (HPVs) have been found in many, but not all, tumours of the oral cavity, nose, pharynx and larynx, the true role of HPV in malignant tumours of the head and neck is still unclear. The presence of HPV DNA was investigated in 45 fresh squamous cell carcinoma (SCC) specimens and in 29 normal mucosa specimens collected from 45 primary laryngeal SCC patients. HPV DNA was detected using the polymerase chain reaction (PCR) with consensus primers that detect HPV types 6, 11, 16 and 18.9 of the 45 patients (20%) were HPV positive; the presence of HPV was also detected in the corresponding normal laryngeal mucosa of four of the 29 specimens (14%). No statistically significant differences were found between the presence of HPV DNA in normal specimens and in neoplastic mucosa specimens. No correlation was found between HPV DNA positive tumours and size, T classification, lymph node involvement and histological grading. This study adds further evidence suggesting a possible role of HPV DNA infection in laryngeal carcinogenesis.

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.

Anti-endothelial autoantibodies in patients with sudden hearing loss.

OBJECTIVES/HYPOTHESIS: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vascularis. The authors investigated the presence of antiendothelial cell antibodies (AECA) to see if immune-mediated vasculitis may play a role in human sudden HL. STUDY DESIGN: A prospective study in patients with sudden HL. METHODS: Fifteen consecutive patients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Extensive audiovestibular, imaging, microbiological, immunological, and routine examinations were performed. AECA were detected on rat kidney tissue sections on the sera collected at -20 degrees C. RESULTS: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive (P = .023). CONCLUSIONS: In patients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis.

The contribution of immunoscintigraphy to the diagnosis of head and neck tumours.

Immunoscintigraphy with 111In-F(ab')2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n = 14), recurrences (n = 3) and suspected posttherapy lymph node metastases (n = 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100% and a sensitivity of 90%. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer.

Facial nerve paralysis in acute otomastoiditis as presenting symptom of FAB M2, T8;21 leukemic relapse. Case report and review of the literature.

Granulocytic sarcoma (chloroma) is a rare solid, extramedullary tumour composed of immature granulocytes, occurring during granulocytic leukemia. Leukemic involvement of the temporal bone is not uncommon and may present in a variety of ways. Symptomatic facial nerve paralysis is one of these. The authors report a case of facial nerve paralysis as the presenting symptom of leukemic relapse in a 16-year-old white male, affected by acute myelogenous leukemia FAB M2, karyotype 46xy, T8;21.

Low serum folate levels: a risk factor for sudden sensorineural hearing loss?

OBJECTIVE: Ischemic vascular damage of the inner ear is one of the known causes of sensorineural sudden hearing loss (SSHL). Folate is an emerging risk factor associated with an increased risk of vascular damage. The aim of this study was to investigate whether low serum folate levels are associated with SSHL. MATERIAL AND METHODS: Serum folate levels were determined in 43 patients with SSHL and in 24 controls. RESULTS: Folate levels were found to be significantly lower in SSHL patients than in controls (mean difference -1.96 ng/ml; 95% CI -3.31, -0.59 ng/ml; p = 0.006). No significant relationship between folate levels and either sex, age, cigarette smoking, alcohol consumption or hypertension was observed, while a significant relationship was found between low folate levels and high homocysteine (HCY) levels in all 43 patients (p < 0.01). The potential influence of low folate levels on hearing impairment in SSHL patients can be explained by the effects on HCY metabolism and the diminution of folate antioxidant capacity. CONCLUSION: Further studies are needed to elucidate whether low folate levels can be considered a risk factor for SSHL.

Can chronic nasal obstruction cause dysfunction of the paratubal muscles and otitis media? An experimental study in developing Wistar rats.

OBJECTIVE: To quantitatively analyze modifications of the paratubal muscles in developing Wistar rats following nasal obstruction. MATERIAL AND METHODS: Twenty-four Wistar rats were used. Twelve were examined at 6, 8 and 12 weeks after birth and were considered normal controls. The nostrils of the remaining 12 rats were bilaterally obstructed by means of a synthetic resin 28 days after birth. The animals were sacrificed at either 2, 4 or 8 weeks after nostril occlusion. Serial sections were made in the dorsoventral plane and stained with hematoxylin-eosin. Four 5 x 5 microm2 areas, selected within the paratubal muscles, were histologically analyzed and the number of muscular fibers was counted manually. RESULTS: The number of tensor veli palatini muscle fibers progressively decreased in the obstructed rats compared with age-matched normal controls and in those that had been obstructed for 4 and 8 weeks these reductions were statistically significant. CONCLUSION: The correct development of the paratubal muscles seems to be linked to physiological nasal breathing and is negatively affected by oral breathing.

Misleading clinical features in Wegener's granulomatosis. A case report.

Wegener's granulomatosis is a systemic vasculitis that may present with a variety of findings and be difficult to diagnose. We report a case of a patient who presented with serous otitis media and subsequently developed a suspected primary lung tumour. Thoracotomy and pulmonary mass excision were required to establish the diagnosis. Otological manifestations of Wegener's granulomatosis, differential diagnosis, pathological findings and c-ANCA test role are discussed.

Early diagnosis and stage-adapted treatment of Wegener's granulomatosis.

A case of Wegener's granulomatosis (WG) presenting with hearing loss and right facial nerve palsy is reported. The definitive diagnosis was based upon clinical data and serum cANCA and AECA detection. Early assessment of WG prevented surgical facial nerve decompression to treat a chronic otitis media complication. Immunosuppressive therapy with steroids, cyclophosphamide and methotrexate was required for relief of clinical symptoms and cANCA negativity as an expression of disease remission. The effectiveness of co-trimoxazole for preventing relapses of WG is discussed.

Sudden hearing loss in a patient hepatitis C virus (HCV) positive on therapy with alpha-interferon: a possible autoimmune-microvascular pathogenesis.

Alpha interferon (alpha-IFN) is used for the treatment of various systemic disorders. Side-effects of alpha-IFN therapy can involve numerous organ systems, but sudden hearing loss has only once been recorded. We report a case of sudden hearing loss occurring in a patient with chronic hepatitis C treated with alpha-IFN and recovered five days after the discontinuation of this agent. This is the first record of anti-endothelial cell antibodies detection in a patient with sudden hearing loss. The finding of anti-endothelial cell antibodies suggests an association between sudden hearing loss and microvascular damage during interferon therapy.

[Pleomorphic adenoma of the lower turbinates: clinical case and review of literature]. / Adenoma pleomorfo del turbinato inferiore: caso clinico e revisione della letteratura.

A case of pleomorphic adenoma of the lower turbinate salivary glands is presented. A careful review of the literature has revealed that this is a highly unusual site for such neoplasms. The scarcity of symptoms is underlined as the lesion can long go unrecognized. Moreover, it is pointed out that, since only a small number of cases have thus far been presented for this benign lesion the prognostic factors indicating a clinical evolution to malignancy are as yet unknown. For this reason the authors feel it advisable to perform conservative surgery and carry out a careful follow-up.

[Hemangiopericytoma of parapharyngeal space]. / Emangiopericitoma dello spazio parafaringeo.

The parapharyngeal space is a rare site of parapharyngeal neoplasms: their diagnosis and therapeutic treatment offer peculiar challenges. Parapharyngeal tumours may be primary, metastatic or diffused with regaed continuity. They are mostly benign (mixed, neurogenic, vascular tumours, etc.) rather than malignant neoplasms (adenocystic carcinoma, adenocarcinoma, lymphoma, etc.). In order to diagnosis parapharyngeal tumours differentially it is important to consider very rare type of neoplasms such as hemangiopericytomas. In this paper the Authors describe a case of hemangiopericytoma of the parapharyngeal space indicating the main diagnosis procedures, especially CT scan, Magnetic resonance and angiography. They discuss pathological aspects with particular regard to the differential diagnosis between benign and malignant tumour of this kind as well as prognoses. The Authors also describe surgical treatment in relation to particular parapharyngeal localization.

Correlation between NRT measurement and behavioural levels in patients with the Nucleus 24 cochlear implant.

Aim of this study was to determine the relationship between the electrically evoked whole nerve action potential (EAP) and T- and C-level for subjects using the Nucleus 24 cochlear implant system. EAP thresholds were measured using the Neural Response Telemetry system of the Nucleus 24 device. Twelve Nucleus 24 cochlear implant users took part in this study. EAP thresholds were compared with the behavioural measures of T- and C-levels used to programme the speech processor. The EAP and the T- and C-levels were obtained, on the same day, 1 month after cochlear implant activation. EAP thresholds were seen to fall between the T- and C-level. On average, EAP thresholds fell at 72% of the map dynamic range. The majority of absent answers were found in three of the 12 patients, and out of a total of 195 activated electrodes an EAP was recorded in 169. These data show that Neural Response Telemetry is a valuable clinical tool in the Nucleus cochlear implant system, providing information concerning integrity of the implant and status of the peripheral auditory nerves.