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Purpose: To assess preoperative features that could predict the audiological outcome after cochlear implantation in the elderly, in terms of pure tone audiometry, speech audiometry, and speech perception performance., Methods: All available records of patients with cochlear implants aged 65 or more at the time of their implantation at our Institution were reviewed (50 patients, mean age 70.76 ± 4.03 years), recording preoperative clinical features. Pure tone audiometry, speech audiometry, and speech perception performance 1 year after cochlear implant activation and fitting were used as outcome measures., Results: No statistically significant association emerged between clinical features and pure tone audiometry. On univariate analysis, progressive sensorineural hearing loss of unknown origin was associated with a better outcome in terms of speech audiometry and speech perception performance (p = 0.035 and p = 0.033, respectively). On multivariate analysis, progressive sensorineural hearing loss retained its independent prognostic significance in terms of speech perception performance (p = 0.042). The discriminatory power of a two-variable panel (age and etiology of hearing loss) featured an AUC (ROC) of 0.738 (an acceptable discriminatory power according to the Hosmer-Lemeshow scale)., Conclusions: A progressive sensorineural hearing loss of unknown origin was associated with a better outcome in terms of speech perception in the elderly in our case study. Further features that can predict audiological outcome achievable with cochlear implants in the elderly are desirable to perform adequate counselling and rehabilitation programs.

Surgery for early-intermediate oropharyngeal squamous cell carcinoma (OPSCC) may involve using transoral endoscopic approaches or open surgical procedures. "Lateral pharyngotomy" (LP) is an open surgical approach that improves exposure of the oropharyngeal region, while avoiding mandibulotomy. The aim of the present study was to retrospectively analyze our experience with the surgical treatment of early-intermediate OPSCC using the LP approach, and to investigate the potentially prognostic clinical and/or pathological factors that might identify patients at higher risk of recurrence after primary surgery. Sixty-four patients with previously untreated early-intermediate (pT1-T2-T3) OPSCC consecutively underwent partial pharyngectomy using a LP approach, performed by the same surgical team at a tertiary head and neck oncology center (Otolaryngology Unit, Vittorio Veneto Hospital, Italy). The 2-year disease-specific survival rates were 86% for stage I-II and 77% for stage III-IV disease. All patients who experienced locoregional or distant metastases died of their disease, while no patients died of any complications of the treatment. Postoperative complications occurred in 25 patients (39%), the most common being pharyngocutaneous fistula. All but one of the patients experienced a complete recovery of oral food intake. In conclusion, the LP approach to oropharyngeal cancer could be a valid open surgical alternative to oropharyngectomy with mandibulotomy for: (a) patients with early-intermediate OPSCC in whom oropharyngeal exposure proves difficult, and/or who are not eligible for transoral endoscopic surgery; (b) HPV-negative OPSCCs; and, ((c) patients unfit for or refusing chemoradiotherapy.)

Our primary aim was to use nasal cytology to compare a group of woodworkers with a group of unexposed subjects to see whether wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary aim was to seek any differences in nasal symptoms or nasal cytology between workers exposed to softwood vs hardwood dust, thereby comparing the inflammatory harmful potential of the two woods. Among 117 woodworkers at factories in the Veneto region (Italy), 40 exposed to either softwood or hardwood dust were assessed by means of a questionnaire, nasal cytology, and personal wood dust sampling, and compared with 40 unexposed controls. Woodworkers reported significantly more nasal symptoms than controls (p = 0.0007). The woodworker group's nasal smears contained significantly more neutrophils (p < 0.00001) and lymphocytes (p = 0.02) than the control group's. The softwood workers had significantly lower levels of personal exposure to wood dust than the hardwood workers (p = 0.04); there were no significant differences in age, history of cigarette smoking, or period of exposure between these two sub-cohorts of woodworkers. A statistical trend indicated that softwood workers had more eosinophils (p = 0.05) and lymphocytes (p = 0.05) in their rhinocytograms. Nasal cytology revealed chronic inflammatory rhinitis in a significant proportion of woodworkers' enroled in this study. It also suggested a different harmful potential for softwood and hardwood dust. Nasal cytology could prove useful in screening woodworkers for chronic inflammatory rhinitis. Further investigations are needed to examine the role of different types of wood dust in nasal inflammation.

Objectives: To assess whether ultrasound elastography (USE) with strain ratio increases diagnostic accuracy of Doppler ultrasound in further characterisation of cytologically Thy3 thyroid nodules., Methods: In two different university diagnostic centres, 315 patients with indeterminate cytology (Thy3) in thyroid nodules aspirates were prospectively evaluated with Doppler ultrasound and strain ratio USE before surgery. Ultrasonographic features were analysed separately and together as ultrasound score, to assess sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves to identify optimal cut-off value of the strain ratio were also provided. Diagnosis on a surgical specimen was considered the standard of reference., Results: Higher strain ratio values were found in malignant nodules, with an optimum strain ratio cut-off of 2.09 at ROC analysis. USE with strain ratio showed 90.6% sensitivity, 93% specificity, 82.8% PPV, 96.4% NPV, while US score yielded a sensitivity of 52.9%, specificity of 84.3%, PPV 55.6% and NPV 82.9%. The diagnostic gain with strain ratio was statistically significant as proved by ROC areas, which was 0.9182 for strain ratio and 0.6864 for US score., Conclusions: USE with strain ratio should be considered a useful additional tool to colour-Doppler US, since it improves characterisation of thyroid nodules with indeterminate cytology., Key Points: • Strain ratio measurements improve differentiation of thyroid nodules with indeterminate cytology • Elastography with strain ratio is more reliable than ultrasound features and ultrasound score • Strain ratio may help to better select patients with Thy 3 nodules candidate for surgery.

Even after appropriate surgical therapy, a significant number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrences. The end-point of this prospective study was to apply univariate and multivariate statistical models to identify clinical, pathological, and laboratory variables that could predict CRSwNP recurrence after endoscopic sinus surgery. The study enrolled 143 patients between 2010 and 2013, who were all treated by the same surgeon for CRSwNP. Twenty-one patients developed recurrent polyposis. The recurrence rate was significantly higher for the eosinophilic than for the non-eosinophilic type (p = 0.020). Among the patients who developed a recurrence, the disease-free interval was significantly shorter for those with eosinophilic-type polyposis (p = 0.003). Univariate statistical analysis disclosed significant associations between CRSwNP recurrence and age (p = 0.035), allergy (p = 0.014), and eosinophilic granulomatosis with polyangiitis (p = 0.01). The multivariate model showed that only histological evidence of the eosinophilic type of CRSwNP retained an independent prognostic significance in relation to recurrent polyposis (p = 0.033). Judging from our results, it is reasonable to consider both stricter follow-up protocols and postoperative adjuvant medical treatments for patients with a histological diagnosis of eosinophilic-type CRSwNP.

Total laryngectomy (TL) is often still recommended as a salvage approach for recurrent laryngeal squamous cell carcinoma (LSCC). Considering LSCC recurrences after the failure of primary transoral laser microsurgery (TLM), open partial horizontal laryngectomy (OPHL) could be a valid alternative to TL in selected patients. The aim of the present study was to analyze retrospectively the oncological outcome of a consecutive series of 17 patients treated at the Otolaryngology Unit of Vittorio Veneto Hospital (Italy) with OPHL after primary TLM had failed. Nine patients (53 %) had no further recurrences after salvage OPHL. Eight patients had a second recurrence of LSCC after OPHL, and five of them were cured by further salvage treatment, while the other three died of their disease. We found an overall and disease-specific survival both of 82 % and a loco-regional control rate and an ultimate organ preservation rate of 82 and 70 %, respectively. Patients who underwent two-stage bilateral cordectomy for primary glottic carcinoma showed a trend towards a higher rate of second recurrences, a lower ultimate organ preservation rate and a shorter disease-free survival after salvage OPHL. Further studies on larger cohorts of patients are needed to identify potential clinical and/or pathological prognostic parameters capable of pinpointing patients at higher risk of second recurrences after salvage OPHL in cases where TLM has failed. A salvage TL might be reasonably proposed as a first salvage choice in such cases.

Laryngeal squamous cell carcinoma (LSCC) recurrences are very difficult to manage in elderly patients (age ≥65 years), because treatment carries significant morbidity and mortality. The aim of this study was to develop a panel of parameters (clinicopathological variables or biomarkers) to improve our ability to detect elderly patients at higher risk of LSCC recurrence. Maspin, nm23-H1, and CD105 were investigated using immunohistochemistry on surgical specimens from 46 elderly patients treated for LSCC. After univariate analysis identified parameters associated with LSCC recurrence, a multivariate prognostic model was constructed. At univariate analysis, a higher recurrence rate was significantly associated with nm23-H1 nuclear expression in carcinoma cells ≤2.0% (p = 0.01), CD105 expression in intratumoral vascular endothelial cells ≥5.28% (p = 0.04), and pN+ status (p = 0.04). Multivariate modeling confirmed that nuclear nm23-H1 ≤2.0% (p = 0.009) and CD105 ≥5.28% (p = 0.013) had a negative prognostic significance in terms of disease recurrence, while pN+ status showed a trend toward significance (p = 0.05). We thus obtained a panel comprising two biomarkers and neck lymph node status that revealed an excellent discriminatory power [AUC (ROC) of 0.81] in terms of the risk of LSCC recurrence. The panel achieved a specificity of 96% and a positive predictive value of 93%. We identified a panel with an excellent discriminatory power in identifying elderly patients at higher risk of recurrence after treatment for LSCC. These patients would benefit from a more aggressive primary treatment.

Despite appropriate surgical therapy, 5-10 % of patients with chronic rhinosinusitis (CRS) and nasal polyps (NP) experience disease recurrences. It has been suggested that angiogenesis may relate to the pathogenesis and prognosis of CRS with NP. Endoglin (CD105) is a component of the receptor complex of transforming growth factor-beta, a pleiotropic cytokine that modulates angiogenesis. A series of patients treated surgically for CRS with NP was analyzed to assess the relationship between CD105 expression, main clinicopathological features, and recurrence rate. The immunohistochemical expression of CD105 was assessed in 70 patients consecutively operated for CRS with NP. In the univariate setting, the presence of CD105 (1/0) showed a trend towards a significant association with increasing NP dimensions (p = 0.054). Intensity of CD105 reaction was also significantly associated with NP size (0.04) and with an eosinophilic histology (p = 0.048). In our multivariate setting, only asthma (p = 0.016), hypereosinophilia (p = 0.022), and preoperative polyposis score (p = 0.046) retained their independent prognostic significance in relation to NP recurrence. Further efforts are needed to elucidate the biological, angiogenic and proliferative mechanisms behind recurrent NP. Our preliminary results support the clinical utility of extra postoperative care, in terms of closer follow-ups and medication with oral anti-histamines, topical and/or oral steroids, and antileukotrienes in patients with asthma, advanced nasal polyposis at presentation, and serum hypereosinophilia.

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant local recurrence rate even in patients with postoperative pathology reports of free surgical margins. This raises the question of how "free" negative margins should be to be oncologically safe, especially in bone tissue. A potential role for relaxin-2 hormone in tumor-driven osteolysis has recently been reported. The aim of this study was to assess the prognostic role of relaxin-2 expression in TBSCC tissue specimens and pathologically negative bone margins. Relaxin-2 immunohistochemical expression was assessed in 25 consecutively operated TBSCC patients. Several pathological variables correlated with recurrence rate (pT stage, dura mater involvement), disease-free survival (DFS) (pT stage, pN status, grade, and dura mater involvement), and disease-specific survival (DSS) (pT stage, pN status, grade, and dura mater involvement). The recurrence rate, DFS, and DSS did not correlate with relaxin-2 expression in TBSCC specimens or pathologically negative bone margins. Although local recurrence in TBSCC could relate to neoplastic bone invasion not apparent on conventional pathological investigations, the present preliminary findings seem to rule out any role of relaxin-2 in mediating this local aggressiveness. Molecular mechanisms of TBSCC recurrence after curative treatment should be further investigated.

With a worldwide incidence estimated at 8-15 per 100,000 population a year, idiopathic sudden sensorineural hearing loss (ISSHL) is a common clinical finding for otologists. There is a shortage of information on the clinical factors capable of predicting hearing recovery and response to therapy. The aim of the present study was to retrospectively investigate the prognostic value of clinical variables in relation to hearing recovery, in a cohort of 117 consecutive patients with ISSHL. Clinical parameters (signs, symptoms, comorbidities and treatments) and audiometric data were analyzed with univariate and multivariate statistical approaches for prognostic purposes to identify any correlation with hearing recovery, also expressed according to the Wilson criteria. Univariate analysis showed that age and hypertension were significantly related to hearing outcome (p = 0.004 and p = 0.015, respectively). Elderly patients and those with hypertension were at higher risk of experiencing no hearing recovery (OR = 3.25 and OR = 2.89, respectively). Age was an independent prognostic factor on multivariate analysis (p = 0.007). Tinnitus as a presenting symptom showed a trend towards an association with hearing recovery (p = 0.07). The treatment regimen, the time elapsing between the onset of symptoms and the start of therapy (p = 0.34), and the duration of the treatment (p = 0.83) were unrelated to recovery on univariate analysis. Among the parameters considered, only age was significantly and independently related to hearing outcome. There is a need for well-designed, randomized clinical trials to enable an evidence-based protocol to be developed for the treatment of ISSHL.

The aim of the present study was to investigate if any of the three awake procedures [fiberoptic nasopharyngoscopy with modified Müller Maneuver (FNMM), nasal snoring endoscopy (NSE), or oral snoring endoscopy (OSE)] could efficiently predict the grade or pattern of upper airway (UA) collapse found with drug-induced sleep endoscopy (DISE), which is considered by many authors as the current gold standard in optimizing obstructive sleep apnea syndrome (OSAS) patient selection for UA surgery. Twenty consecutive patients (simple snorers and OSAS patients) were studied with FNMM, NSE, OSE, and DISE. The inter-test agreement was evaluated with Cohen's kappa coefficient (κ). In the current series, we found that NSE and OSE were better than FNMM in predicting the pattern of collapse found with DISE. A significant pattern agreement between NSE and DISE was present in all sub-sites, and the agreement was measured with a scale proposed by Landis and Koch as: moderate in velo- and oropharynx (κ = 0.52, p = 0.001, and κ = 0.47, p = 0.003, respectively), and substantial in hypopharynx (κ = 0.63, p < 0.00001). Comparing OSE with DISE, the pattern agreement was almost perfect at oropharyngeal level (κ = 0.82, p < 0.00001), and moderate at hypopharyngeal level (κ = 0.55, p = 0.0002); while a trend towards significance was found at velopharyngeal level (κ = 0.20, p = 0.07). FNMM showed a fair pattern agreement with DISE only at oropharyngeal level (κ = 0.31, p = 0.009); while in the other sub-sites, no significant agreement was found. NSE and OSE are new promising diagnostic tools in OSAS patients. Further investigations are needed to see if they could predict the effectiveness of UA surgery.

Deep neck infections (DNI) spread along fascial planes and involve neck spaces. Very few studies have investigated potentially prognostic factors using multivariate statistical models. Our aim was to analyze 282 consecutive cases of DNI using multivariate (logistic) statistical models to identify independent significant factors influencing prognosis in terms of complications and long-term hospitalization (>6 days). In our series, only involvement of more than one neck space was independently significant in prognosticating complications of DNI (odds ratio [OR] 2.46). The presence of comorbidities (OR 2.13), non-odontogenic sites of origin (OR 1.88), leukocyte counts above 11.0 cells × 10(9)/L at presentation (OR 3.57), and the need for both medical and surgical treatments (OR 4.66) was significantly and independently prognostic of long hospital stays. Multivariate analysis can distinguish between risk factors and their relative contribution to outcome. The few published studies using multivariate models to analyze DNI prognosis considered quite large cohorts, but no clinical variables persistently revealed an independent significant prognostic role. This evidence seems to underscore the complex interdependence of several clinical variables in contributing to DNI prognosis, and the heterogeneity of the diagnostic/therapeutic approaches adopted.

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.

Objective: Evaluation of the diagnostic efficacy and interobserver agreement of Q-elastography in the differentiation of benign from malignant thyroid nodules., Methods: A total of 344 thyroid nodules in 288 patients were examined with grey-scale and colour Doppler ultrasound (CDUS) and Q-elastography by two independent operators. Nodules with hypoechogenicity, poorly defined margins, microcalcifications, and intralesional vascularity were classified as suspicious. Diagnostic performances of CDUS features and Q-elastography for predicting thyroid malignancy were estimated using ROC analysis. Cytology or histopathology was the reference standard. Interobserver agreement in the evaluation of CDUS and Q-elastography was assessed using Cohen's k-statistic., Results: Q-elastography showed excellent diagnostic performance for the prediction of thyroid malignancy, with sensitivity of 93 % and specificity of 92 % for operator 1 (best cutoff at 2.02), and sensitivity of 84 % and specificity of 79 % for operator 2 (best cutoff at 1.86). Performance of Q-elastography was superior to that of CDUS. Reproducibility of the findings was excellent for both Q-elastography and CDUS features as assessed with Cohen's k, which was highest for strain ratio measurements (0.95) and lowest for the echogenicity score (0.83)., Conclusions: Q-elastography showed excellent performance. It is a valid and reproducible diagnostic method as well as a promising tool for identifying suspicious solid thyroid nodules needing cytological assessment and surgery., Key Points: • Elastography is an additional tool for optimal characterisation of malignant thyroid nodules. • The use of semiquantitative elastographic evaluation increases the diagnostic performance, • The interobserver agreement of quantitative elastography can be considered to be good.

Technological advances in ultrasonography (US) in recent years has allowed for improvements to the imaging quality of gray-scale ultrasound and the development of more advanced forms of this imaging technique such as 3D and Doppler US. These improvements mean that US now has an accepted place in rheumatology not only in diagnosis, but also in the determination of disease progression and pathology and in facilitating guidance of interventional therapies. The increasing use of US-guided intervention by rheumatologists in the last 20 years is evidenced by the almost exponential increase in the number of publications in the relevant subjects.

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells' metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23-H1 expression was lower in patients with recurrent disease than in patients without it (statistical trend, p = 0.07). The disease recurrence rate was significantly higher (p = 0.021) and the DFS shorter (statistical trend, p = 0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was 9.16. Nm23-H1 warrants further investigation of its potential role as a predictive biomarker with a view to providing tailored treatments after surgery, such as combinations of chemotherapy and RT instead of RT alone, in patients whose LSCCs have low or no Nm23-H1 expression.

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.

The aim of the present investigation was to analyze the oncological results of a series of early stage glottic carcinomas treated with CO(2) laser-assisted endoscopic surgery. We focused on prognosis factors with significant impact on local control and disease-free survival (DFS). This retrospective study was conducted on a series of 177 consecutive patients with pT1-T2 glottic carcinomas treated with CO(2) laser-assisted endoscopic surgery in the period 2000-2007. All considered patients had at least a 24-month follow-up period (mean follow-up 49.1 ± 23.0 months). The overall survival and the disease-specific survival rates were respectively 90.8 and 98.8%. The rates of local control with primary laser surgery, ultimate local control with laser alone, and laryngeal preservation were 86.3, 94.3, and 97.7%, respectively. Arytenoids (p = 0.006) and limited subglottic involvements (p = 0.0002) have a significant impact on DFS. Endoscopic laser surgery is the gold standard in the treatment of early glottic carcinoma because of high local control rates with laser alone, day surgery modality, very low morbility, good post-operative voice quality in most of the cases, and low costs.

Programmed cell death 4 (PDCD4) has recently been demonstrated to be a new tumor suppressor gene involved in colon carcinogenesis. PDCD4 immunohistochemical expression was assessed in 300 polypoid lesions of the colon mucosa (50 hyperplastic polyps [HP], 50 serrated adenomas [SA], 50 tubular adenomas with low-grade-intraepithelial neoplasia [LG-IEN], 50 tubular adenomas with high-grade-IEN [HG-IEN]), and in 50 colon adenocarcinomas (CRC). As normal controls, we considered 50 biopsy samples obtained from patients with irritable bowel syndrome (N). We further investigated PDCD4 messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (PCR) in a different series of N, LG-IEN, HG-IEN, and CRC biopsy samples. miR-21 expression (an important PDCD4-expression regulator) was also determined by quantitative real-time PCR and in situ hybridization. Normal colocytes and HP featured strong PDCD4 nuclear immunostaining whereas a significantly lower PDCD4 nuclear expression was observed in dysplasia (low- and high-grade adenomas and SA) and invasive CRC. PDCD4 immunostaining and mRNA levels decreased significantly as the phenotypic changes occurring during colon carcinogenesis progressively increased (p < 0.001). As expected, miR-21 expression was significantly upregulated in preneoplastic/neoplastic samples, consistent with PDCD4 downregulation. These results consistently support the use of nuclear PDCD4 immunohistochemical downregulation as a novel biomarker for the diagnosis of dysplastic/neoplastic lesions in colon biopsy samples.

Despite advances in laryngeal squamous cell carcinoma (LSCC) treatment, patient survival has not improved in the last two decades. Novel, more effective strategies should be based on receptor-mediated LSCC-targeted therapy. The epidermal growth factor receptor (EGFR) is the most widely studied molecular target. MASPIN multifaceted anti-tumor effects have been rarely evaluated in LSCC. The aims of this study were to investigate EGFR and MASPIN expression and the role of sub-cellular MASPIN localization in LSSC. MASPIN and EGFR expression and the sub-cellular localization of MASPIN were assessed using a computerized image analysis system in 108 consecutive cases of operable LSCC. The rates of occurrence of lymph node metastases and recurrent disease were lower in patients with a nuclear pattern of MASPIN expression (p = 0.004, p = 0.0028). As expected, the loco-regional recurrence rate was lower in N0 patients (p = 0.009), but the disease recurrence rate was even lower in N0 patients with a nuclear localization of MASPIN (p = 0.020). Disease-free survival was longer in cases of LSCC with a nuclear MASPIN pattern (p = 0.003). The intensity of EGFR reactivity and the EGFR area fraction were unrelated to the clinico-pathological and prognostic parameters in LSCC. A nuclear MASPIN pattern is a promising prognostic indicator in LSCC, but further evidence is needed before elective neck dissection can be considered for cN0 LSCCs with a non-nuclear MASPIN pattern. Although a better understanding of the mechanisms behind sub-cellular MASPIN localization is mandatory, re-activating nuclear MASPIN in association with specific chemotherapeutic agents may be an important goal in the treatment of LSCC.

MASPIN, a member of serpin superfamily, has multifaceted biological functions and an unique tumour suppressing activity. Experimental evidences showed that MASPIN suppresses tumour growth, angiogenesis, invasion and metastasis. Only a very limited number of studies considered MASPIN expression in the upper aero-digestive tract carcinomas. It was recently found that nuclear localization of MASPIN was significantly associated with lower recurrence rate and longer disease-free interval in laryngeal carcinoma. The present study investigated the biological and prognostic role of MASPIN in relation to its subcellular localization in oral carcinoma. Sub-cellular pattern of distribution of MASPIN, nuclear and cytoplasmic MASPIN expressions were immunohistochemically determined in 56 consecutive cases of oral carcinoma. Statistical analysis found a significant association between pN-stage and recurrence of disease (P=0.032) and a significantly longer disease-free interval in pN0 patients than in pN+ ones (P=0.038). None of the subcellular expressions of MASPIN was significantly correlated with recurrence of disease and disease-free interval in our series of oral carcinomas. Sixty-one percent of pN0 cases was strongly MASPIN-positive in the cytoplasm of primary carcinoma cells, 33% of the pN+ cases was MASPIN-positive in the cytoplasm. Statistical analysis found a significant association between MASPIN cytoplasmic expression and pN-stage (P=0.032). Negative MASPIN immunoreactivity in carcinoma cells cytoplasm may be useful to identify patients at risk of disease disseminating to neck lymph nodes. Further investigations are necessary to understand the biological role of cytoplasmic MASPIN localization in oral carcinoma.

Several studies supported the hypothesis that an autoimmune response may be a pathogenetic factor in Meniere's disease occurrence. It has been demonstrated that the endo-lymphatic sac has an important role in the immuno-mediated reaction and it has also become evident that an immunological mechanism may be involved in the development of endo-lymphatic hydrops. The present study was carried out in order to analyse the validity of serological non-specific immune tests in determining the possible role of immune pathology in 200 Meniere's suffering patients. The immune activity was investigated determining the erythrocyte sedimentation rate (ESR), the C-reactive protein levels, the rheumatoid factor, the serum immunoglobulin levels by group, the complement levels, the lymphocyte sub-populations, the cryoglobulines, the circulating immune complexes (CIC), organ and non-organ auto-antibodies. Levels of Ig, ESR, C-reactive protein, rheumatoid factor, complement fractions and cryoglobulines were either negative or non-significant in the considered cohort of Meniere's disease suffering patients. On the other hand, in more than half of the sample group high values of CIC were found. Data concerning T-lymphocyte sub-population indicates a clear increase in T-helper compared to T-cytotoxic cells, with an increase in the CD4/CD8 ratio. The datum of particular interest concerns analysis of T-cells activation complexes. Our present findings show that early activated T-lymphocytes change and in particular changes occur in the expression of the interleukin-2 receptor. Moreover, it seems to be possible to correlate the alteration of the immunological tests and the phase of the disease. Present data showed that the immunological factor should be considered a relevant element in most of the cases of Menière's disease.