Search

Background: The purpose of this study is to evaluate whether demographics, lifestyle habits, clinical data and alcohol dehydrogenase polymorphisms rs1229984 and rs1573496 associated with first primary head and neck (HNC) are associated with overall survival, recurrence, and second primary cancer (SPC). Methods: We conducted a follow-up study in five centres including 801 cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for overall survival, recurrence and SPC. Results: Five-years overall survival was 62% for HNC cases, 55% for oral cavity, 53% for oropharynx, 41% for hypopharynx, and 71% for larynx. Predictors of survival were older ages (HR. =. 1.18 for 5 years increase; CI: 1.07-1.30), higher tumour stage (HR. =. 4.16; CI: 2.49-6.96), and high alcohol consumption (HR. =. 3.93; CI: 1.79-8.63). A combined therapy (HR. =. 3.29; CI: 1.18-9.13) was associated with a worst prognosis for oral cavity cancer. The only predictor was higher tumour stage (HR. =. 2.25; CI: 1.26-4.03) for recurrence, and duration of smoking (HR. =. 1.91; CI: 1.00-3.68) for SPC. ADH1B rs1229984 polymorphism HRs for HNC and oesophageal cancer death and for alcohol related cancer death were 0.67 (95% CI: 0.42-1.08), and 0.64 (95% CI: 0.40-1.03), respectively. Conclusions: The survival expectation differs among HNC sites. Increasing age and stage, and high alcohol consumption were unfavourable predictors of HNC survival overall. Duration of tobacco consumption before the first primary tumour was a risk factor for SPC.

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 (chi(2) = 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.

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.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10-7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10-8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10-8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10-8; rs1229984-ADH1B, p = 7×10-9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility. © 2011 McKay et al.

Wegener's granulomatosis (WG) is a unique clinicopathological disease characterized by necrotizing granulomatous vasculitis of the respiratory tract, pauci-immune necrotizing glomerulonephritis and small-vessel vasculitis. Owing to its wide range of clinical manifestations, WG has a broad spectrum of severity that includes the potential for alveolar hemorrhage or rapidly progressive glomerulonephritis, which are immediately life threatening. WG is associated with the presence of circulating antineutrophil cytoplasm antibodies (c-ANCAs). The most widely accepted pathogenetic model suggests that c-ANCA-activated cytokine-primed neutrophils induce microvascular damage and a rapid escalation of inflammation with recruitment of mononuclear cells. The diagnosis of WG is made on the basis of typical clinical and radiologic findings, by biopsy of involved organ, the presence of c-ANCA and exclusion of all other small-vessel vasculitis. Currently, a regimen consisting of daily cyclophosphamide and corticosteroids is considered standard therapy. A number of trials have evaluated the efficacy of less-toxic immunosuppressants and antibacterials for treating patients with WG, resulting in the identification of effective alternative regimens to induce or maintain remission in certain subpopulations of patients. Recent investigation has focused on other immunomodulatory agents (e.g., TNF-alpha inhibitors and anti-CD20 antibodies), intravenous immunoglobulins and antithymocyte globulins for treating patients with resistant WG.

As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN).

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.

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 mum(2) 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.

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.

Objectives-The purpose of this report is to describe an example of angiosarcoma (AS) of the submandibular salivary gland. The clinical and immunohistopathologic features of these lesions are also reviewed.Material and Methods-A 17-year-old male high school student was admitted to our clinic with a 1-year history of a slow growing, tender mass in the left submandibular region. Physical examination on initial presentation revealed a diffuse soft tissue mass 6 cm in diameter involving the left submandibular region. MRI analysis revealed a mass located superolateral to the submandibular salivary gland, measuring 4.0 x 2.0 cm(2). The mass was excised completely together with the left submandibular salivary gland. Histopathologic analysis led to a diagnosis of AS. Immunohistochemical studies were also used to determine endothelial cell differentiation. Owing to the lateralized nature of the lesion, a left functional neck dissection was performed and postoperative radiotherapy was planned.Results-AS is a malignant tumor of endothelial cell origin that may occur in any region of the body. The commonest sites include the extremities and the retroperitoneal space, with only 4% of AS tumors arising in the head and neck area. The submandibular salivary gland is an extremely rare location for this tumor. Based on a literature review, this case report represents only the second reported case of AS of the submandibular salivary gland.Conclusions-In most cases, radical surgery and postoperative radiotherapy are advocated to treat patients with AS tumors, with lymph node clearance recommended in cases of lateralized lesions. In some patients, distant metastasis may occur after many years, which necessitates long-term follow-up. The prognosis is poor in most cases of AS.

Background. Human papillomavirus (HPV) infection is suspected to be a risk factor for head and neck, and in particular for laryngeal, carcinogenesis. Cyclin D1 gene (CCND1) overexpression and amplification have been shown to play a role as prognostic factors in many human cancers, among which are head and neck cancers. Methods. A literature review of the role in head and neck cancers of HPV infection and CCND1 overexpression and amplification was undertaken. We have evaluated the extent of the current knowledge in this field under the light of recent acquisitions, in particular, about a correlation between HPV infection, a suspected risk factor, and CCND1 amplification, a frequent mutation (about 20% of laryngeal cancers) and a prognostic factor in laryngeal SCC. Results and Discussion. The significant correlation between HPV infection and CCND1 amplification supports the hypothesis of the involvement of HPV infection in laryngeal carcinogenesis and suggests that HPV positive laryngeal cancers may constitute a different subset of tumors with a peculiar molecular pattern and thus with a different clinical behavior. HPV infection may be considered a synergistic risk factor with smoking and/or alcohol consumption to be investigated in heavy smokers and drinkers, thus contributing to the identification of patient at high-risk for the development of laryngeal cancer who should undergo strict follow-up and primary and secondary prevention. © 2002 Wiley Periodicals, Inc.

inglese

In order to verify whether anti-endothelial cell autoantibodies (AECAs) can be used as serological markers of inner ear vasculitis in sudden sensorineural hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated. All patients underwent a routine general physical examination and extensive audiovestibular, microbiological and immunological investigations. Fourteen normal subjects without a history of HL, autoimmune or metabolic disease served as controls. Detection of AECAs was performed using an indirect immunofluorescence technique. AECA-positive patients were treated with methylprednisone, while AECA-negative patients were treated with a combined regimen of steroids, plasma expander and aspirin. The average hearing recovery for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after treatment and every 3 months thereafter; median follow-up was 12 months (range 9-18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were AECA-positive and thus differed significantly from the normal population in whom only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was associated with being AECA-positive in 8/11 cases. During follow-up, 25/32 patients improved their hearing and 17 of these patients were AECA-negative. The seven cases without hearing improvement were all AECA-positive. In patients with SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may represent a serological marker of vasculitis even if they are not inner ear-specific and even if they represent an epi-phenomenon rather than the only cause of SSHL.

Sudden hearing loss can be found in systemic autoimmune diseases or it can be a symptom of an autoimmune disease of the inner ear. The present work has studied a group of patients with idiopathic sudden hearing loss to determine what role anti-endothelial cell antibodies (AECA) play as markers of immuno-mediated vasculitis of the inner ear. The study involved 32 patients with sudden deafness and 14 controls. The patients underwent otofunctional, neuroradiological, sero-microbiological and immunological testing. Using the indirect immunofluorescence technique, serum AECA were determined within 24 hours of hospitalization and three days after the onset of deafness. AECA positive patients (AECA+) were administered corticosteroid therapy (methylprednisone 1 mg/kg/die) for 1 month. A clinical follow-up was performed, including audiometry, 1 month after discharge and thereafter at three-month intervals (follow-up range: 8-18 months). AECA proved positive in 15/32 patients (47%) and in 2/14 of the controls (14%). The difference between the patients and the controls was statistically significant (p = 0.03). The 7 patient who showed no recovery after 1 month were all AECA+. None of the AECA+ patients showed other symptoms or a worsening of the hearing loss. In conclusion, the determination of non-specific autoantibodies vs. the inner ear, such as AECA, can be considered a useful clinical tool in differentiating between patients with idiopathic sudden hearing loss and those for which a diagnosis of immuno-mediated vasculitis of the inner ear is likely and for which prognosis is particularly unfavorable.