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Background Very few studies have compared blood eosinophil and basophil levels before and after surgery in patients with eosinophilic CRSwNP (eCRSwNP). No investigations seem to have repeatedly measured them pre- and postoperatively in eCRSwNP patients with recurring versus non-recurring disease to examine how their levels evolved. Objective Hence this study to analyze blood eosinophil and basophil levels in patients with eCRSwNP immediately before surgery and afterwards, at 4 months, 1 year, and then yearly up to 5 years. Methods Fifty-one eCRSwNP patients were enrolled, who all had preoperative laboratory data and the results of at least 4 of the 6 scheduled postoperative follow-up tests. Results Seventeen patients had recurrent disease. Blood eosinophil counts (p = 0.005) and percentages (p = 0.002) were both higher in these patients than in those whose eCRSwNPs did not recur after surgery. Blood basophil counts (p = 0.04) and percentages (p Conclusions In eCRSwNP, the statistical analysis of repeated quantitative laboratory data can shed light on the evolution of a patient’s systemic inflammatory picture in response to previous treatments, and above all to long-term therapies. Long-term monitoring of blood eosinophil and basophil levels could be of significant value when monoclonal antibodies that inhibit IL signaling will widely enter in clinical practice for eCRSwNP treatment to follow the effectiveness of therapy over time.

AIMS In chronic rhinosinusitis with nasal polyps (CRSwNP), tools based on objective evidence, such as histopathology, are needed to assist clinical decision-making. The main aim of this exploratory investigation was to determine whether structured histopathology could be used to classify CRSwNP in homogeneous histological clusters. METHODS AND RESULTS A cohort of 135 CRSwNP patients was assessed, on the basis of clinicopathological features: allergic fungal rhinosinusitis (17 patients); non-steroidal anti-inflammatory drug-exacerbated respiratory disease (19 patients); intrinsic asthma (18 patients); extrinsic asthma (21 patients); allergy (21 patients); histologically eosinophilic (22 patients); and histologically non-eosinophilic (17 patients). For structured histopathology, we considered: the degree of inflammation; eosinophil count; eosinophil aggregates; neutrophil infiltration; goblet cell hyperplasia; basement membrane thickening; fibrosis; hyperplastic/papillary changes; squamous metaplasia; mucosal ulceration; and subepithelial oedema. Cluster analysis identified four distinct sets of cases. On discriminant analysis, the global error rate was 1.48%, and the stratified error rates were 4.34%, 0%, 0%, and 0% for clusters 1, 2, 3 and 4, respectively. Cluster 1 was characterised by infrequent fibrosis (

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. 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. 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). 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.

Background The involvement of the thyroarytenoid (TA) muscle by glottic cancer may be related to an impaired vocal cord mobility, which is classified as cT2 disease. The primary endpoint was to evaluate the prognostic significance of TA muscle involvement in early glottic cancer treated with transoral laser microsurgery (TLM). Methods A review was conducted on a cohort of 209 patients consecutively treated with TLM for early glottic carcinoma. Univariate analysis was used to examine the prognostic meaning of clinical and pathological parameters. Results The statistical analysis showed that TA muscle infiltration correlated significantly with a worse prognosis in terms of recurrence rate and disease-free survival, and this was confirmed even in the subcohort with pT1a glottic cancer. Conclusions Our preliminary findings suggest that it could be considered as a criterion for upstaging a glottic cancer from pT1 to pT2.

BACKGROUND There is a dearth of information regarding the histological and hematological differences between primary and recurrent chronic rhinosinusitis with nasal polyps (CRSwNP). The present study analyzed the histological changes in recurrent CRSwNP in terms of eosinophilic infiltrate, subepithelial edema, goblet cell hyperplasia, and basement membrane thickness. Blood levels of eosinophils and basophils were also measured prior to surgery on both primary and recurrent disease. METHODS Thirty-two consecutive adult patients with nasal polyposis treated with primary surgery who subsequently underwent revision surgery were retrospectively enrolled. RESULTS At primary surgery, a significant positive correlation (all p < 0.05) emerged between all histopathological parameters, and between tissue eosinophil and blood eosinophil counts. A positive correlation between subepithelial edema scores and blood basophil levels (p < 0.025) also came to light. At revision surgery, only basement membrane thickness correlated positively with: (1) tissue eosinophil count; and (2) goblet cell hyperplasia (both p = 0.001). In recurrent disease, there was again a positive correlation between eosinophil counts in tissue and blood (p < 0.05). The mean tissue eosinophil count in recurrent CRSwNP was significantly lower than in the primary disease (p < 0.001). CONCLUSION Our preliminary results support the hypothesis that tissue remodeling due to surgical and medical treatments for CRSwNP is a dynamic process involving important differences in tissue eosinophil counts between primary and recurrent CRSwNP. How tissue remodeling evolves after CRSwNP treatment warrants further investigation, not only in larger series of patients, but also after stratifying patients by the time elapsing since their treatment.

Purpose Whiplash injury is a frequent traumatic lesion occurring mainly in road accidents, which may also cause dizziness severe enough to impact everyday life. Vestibular examination is routinely performed on these patients, although the role of the neuro-otologist is still not clearly defined. The main endpoint of this study was to describe the videonystagmography (VNG) evidence in a large cohort of patients who underwent road traffic whiplash injury. Methods 717 consecutive patients who reported whiplash-associated disorders due to a road traffic accident underwent clinical examination and VNG. Results Patients with saccadic test latency anomalies more frequently complained of vertigo, nausea and cochlear symptoms after trauma (p = 0.031, 0.028 and 0.006), while patients with bilateral vestibular weakness at caloric stimulation more often displayed neck pain after trauma (p = 0.005). Patients complaining of positional or cochlear symptoms or with accuracy anomalies at the saccadic test were significantly older than those with no positional, no cochlear symptoms and without accuracy anomalies (p = 0.022, p = 0.034 and p = 0.001). Patients with bilateral vestibular hypofunction were significantly younger (p Conclusions VNG evidence, particularly vestibular function and saccadic tests, may be related to damage in the cervical region due to whiplash trauma. These findings suggest that neuro-otologic examination may play a role in properly identifying those who suffer damage caused by whiplash trauma, and in characterizing the severity and prognosis of whiplash-associated disorders.

Objectives To evaluate and compare the oncological and functional outcomes of total laryngectomies (TL) performed as first line treatment or for salvage after failure of conservative approaches for treating advanced laryngeal carcinoma (LSCC). Study design A retrospective cohort study. Methods A cohort of 217 patients who underwent TL was divided according to whether the procedure was for primary treatment of their LSCC (101 patients) or for recurrences after conservative surgery or chemo-radiotherapy (116 patients). Results The overall survival rate and disease-specific survival rate were significantly higher in the primary TL group than in the salvage TL group (P = .04 and P = .01, respectively). The recurrence rate was significantly higher and the disease-free survival (in months) was shorter for patients who had salvage TL than for those who had primary TL (P = .00 and P = .01, respectively). The salvage TL group also included significantly more cases of postoperative pharyngo-cutaneous fistula needing salivary stent positioning, and experienced significantly longer hospital stays than the primary TL group (P = .04 and P = .03, respectively). Conclusion Oncological and functional outcomes of primary TL were significantly better than after salvage TL. If salvage TL was performed after conservative surgery had failed, the oncological and functional results were better than after the failure of organ-preserving protocols. This could justify a first attempt at conservative surgery for intermediate-advanced LSCC in selected cases, reserving chemo-radiotherapy only for patients unsuitable for surgery. Level of evidence 4 Laryngoscope, 131:E569-E575, 2021.

Purpose Whiplash is a type of trauma typically caused by a rear end collision in a road accident. About one in two patients who experience whiplash report dizziness and balance problems, which can severely affect their activities in daily life. In industrialized countries, the number of elderly people with a driving license has increased in recent years. The aims of the present study were to describe the video-nystagmographic features in a consecutive series of elderly patients experiencing whiplash injury in a road accident, comparing them with similar injuries in a group of young adults. Methods Twenty-seven patients aged 65 years or more and a control group of 32 young adults between 18 and 21 years old were retrospectively selected. All patients underwent oto-vestibular assessment and video-nystagmography. Results After whiplash trauma, vertigo was more common in elderly patients with decreased peak velocity during the saccadic ocular motricity test (p = 0.017) and with evidence of bilateral vestibular hypofunction after caloric stimulation (p = 0.033). Comparing the two age groups, neck pain after the trauma was reported significantly more by young adults (p = 0.003), who also showed more frequently bilateral vestibular hypofunction (p = 0.025). Conclusion Clinical and instrumental findings seem to support the hypothesis of a functional lesion to the brainstem regions after a whiplash injury. There is an undeniable need, however, for tools capable of objectively assessing the functional or anatomical damage resulting from whiplash-associated disorders, for both clinical and medico-legal reasons.

BACKGROUND The aim of this investigation was to see if a panel of biomarkers (maspin, CD105, and nm23-H1) could be used to stratify patients with laryngeal squamous cell carcinoma (LSCC) in homogeneous disease recurrence risk clusters. METHODS Cluster analysis was used to classify 89 patients based on their immunohistochemical expression of nm23-H1, CD105, and maspin. RESULTS Our analysis identified seven homogeneous clusters: the LSCC recurrence rate was lowest in cluster 6 (non-nuclear maspin pattern, nuclear nm23-H1 expression ≥10%, endothelial CD105 expression

Background In a recent preliminary study, eosinophil and basophil counts were calculated in chronic rhinosinusitis with nasal polyps (CRSwNP) using conventional histologic and immunohistochemical methods. The tissue eosinophil-to-basophil ratio differed in the CRSwNP endotypes considered. Objective To compare the blood eosinophil-to-basophil ratio (bEBR) in a large series of patients with CRSwNP with that in a control group of consecutive rhinological patients with no evidence of nasal, paranasal, or systemic inflammatory disorders. Methods A retrospective study was performed on 334 patients with CRSwNP to compare the preoperative bEBR among different endotypes and with controls (69 cases). Results The mean bEBR was significantly higher in the CRSwNP group than in the control group ( P = .0006). The eosinophil and basophil counts were significantly and directly correlated in the CRSwNP cases ( P = .0000). The mean bEBR was significantly higher in the sub-cohorts of CRSwNP with allergy ( P = .0007), asthma ( P = .0000), and aspirin-exacerbated respiratory disease ( P = .0153). The mean bEBR was significantly higher in the sub-cohort with eosinophilic CRSwNP than in the sub-cohort with noneosinophilic CRSwNP ( P = .0000). Conclusion This study confirms the increasingly interesting role emerging for blood eosinophils and basophils in different CRSwNP endotypes. The bEBR seems to be a parameter worth investigating in different CRSwNP endotypes, because it is significantly higher in patients with allergy, asthma, and aspirin-exacerbated respiratory disease.

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

Background Predicting which patients are at a higher risk for recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most challenging problems in clinical rhinology. A direct association between CRSwNP recurrence rates and serum eosinophil and basophil counts was reported. This study aimed to identify best-fitting cutoffs for binarizing preoperative serum eosinophils and basophils (counts/percentages) for prognostic purposes in cases of CRSwNP recurrence after surgery. A secondary endpoint was to distinguish said cutoffs for prognosticating recurrence in subcohorts of patients with histologically diagnosed eosinophilic/non-eosinophilic CRSwNP. Methods A retrospective study was performed on 280 patients (127 eosinophilic and 153 non-eosinophilic CRSwNP) examining the prognostic role of serum eosinophil and basophil levels. Results For all patients examined, mean preoperative serum eosinophil and basophil levels were significantly higher in patients whose CRSwNP recurred. Patients with eosinophil counts ≥0.24 cells × 109/L and percentages ≥3.7% had odds ratios (ORs) of 2.57 and 2.19 for recurrence; patients with basophil counts ≥0.03 cells × 109/L and percentages ≥0.5% had ORs of 2.19 and 2.24, respectively. Among histologically eosinophilic CRSwNP patients, mean eosinophils and basophils (counts/percentages) were significantly higher in cases that recurred. Serum eosinophil and basophil values were directly correlated. The recurrence odds were OR 2.52 for high eosinophils (≥5.9%), and OR 2.52 and 2.69 for high basophils (≥0.04 cells × 109/L and ≥0.5%, respectively). Conclusion High serum eosinophil and basophil values should be further investigated because they could pinpoint patients at higher risk of eosinophilic-type CRSwNP recurrence. These preliminary results support the increasing interest in the role of basophils in CRSwNP.

Purpose The main aim of this study was to conduct a preliminary investigation into the possible relationship between mTOR and the nuclear tumor suppressor maspin in laryngeal carcinoma (LSCC). Materials and methods mTOR expression and maspin pattern were ascertained, also with the aid of image analysis in 79 consecutive LSCCs. Results Considering the whole series, univariate statistical analysis identified significant differences in the distributions by lymph node status (N0 vs N+) between two subgroups of patients with and without loco-regional carcinoma recurrences (p = 0.017). The log-rank test also showed a shorter disease-free survival (DFS) in pN+ patients (p = 0.0008). mTOR expression was significantly higher in patients whose disease recurred (p = 0.009). The DFS rate was also significantly shorter in cases of LSCC with an mTOR expression ≥11.55% (p = 0.049). Multivariate analysis showed that N status (p = 0.002) and mTOR expression (p = 0.037) retained their prognostic significance in relation to cancer recurrence. In a subgroup of LSCCs with a non-nuclear maspin pattern, mTOR expression was significantly higher in patients whose disease recurred. Multivariate analysis disclosed that N stage (p = 0.012) retained its independent prognostic significance for disease recurrence in this setting. mTOR expression showed a trend towards independent significance in terms of carcinoma recurrence (p = 0.083). Conclusions mTOR inhibitors seem promising for use in cancer therapies. Further investigations are needed on the prospects of incorporating modern mTOR inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.

Although the diagnosis and treatment of sporadic vestibular schwannoma has improved in recent years, no factors capable of predicting its growth have been identified as yet. Endoglin (CD105) is a proliferation-associated protein expressed in angiogenic endothelial cells, and a potential prognostic indicator for several solid tumors. The aim of the present study was primarily to investigate the expression and role of CD105 in a series of sporadic vestibular nerve schwannomas. In 71 consecutive cases of vestibular schwannoma, vessel cross-sectional area and density were calculated from immunohistochemically assessed CD105 expression using image analysis to correlate them with: (i) tumor dimensions; and (ii) tumor growth rate measured on high-resolution contrast-enhanced MRI (ceMRI). Based on assessments of CD105 expression, a significant positive correlation was identified between vessel cross-sectional area and tumor size at the time of surgery (p = 0.0024), and between vessel density and tumor size (p = 0.013). Vessel cross-sectional area (p = 0.0006) and vessel density (p = 0.003) were significantly greater in tumors measuring ≥10 mm in size than in those10 mm. Conversely, when tumor growth rate could be calculated from two or more ceMRI (38 cases), there was no significant correlation between tumor growth rate and cross-sectional vessel area or vessel density as assessed with CD105. Further investigations are needed to ascertain the feasibility of: (i) using circulating endoglin assay to monitor tumor growth; and (ii) targeting neoangiogenesis with anti-endoglin antibodies in sporadic vestibular schwannoma.

Background An example of aggressive eosinophilic polyposis can be found in eosinophilic granulomatosis with polyangiitis (EGPA). Intercellular adhesion molecule-1 (iCAM-1) and vascular cell adhesion molecule-1 (vCAM-1) play a part in mediating the recruitment and adhesion of leukocytes to the vessel wall, and their blood-to-tissue migration under inflammatory conditions. Objective This prospective study compared 3 groups—patients with a definite diagnosis EGPA, non-EGPA patients with phenotypic features suggestive of EGPA, and patients with non-eosinophilic nasal polyposis (controls)—in terms of nasal tissue histology, iCAM-1 and vCAM-1 expression, and blood inflammatory cells. Methods A total of 58 adults underwent sinus surgery (13 patients with EGPA, 23 suspected of having EGPA, and 22 controls). Results Mean tissue eosinophil counts were significantly higher in EGPA patients and suspected cases of EGPA than in controls. Although iCAM-1 and vCAM-1 were diffusely expressed in sinonasal tissues, they did not differently stain EGPA, eosinophilic-type and non-eosinophilic polyposis. Blood basophil and eosinophil levels were high in both the EGPA and the suspected EGPA groups. Intergroup differences were found for eosinophils but not for basophils. Conclusions We do not have yet blood or tissue markers able to differentiate the early phase of EGPA from chronic rhinosinusitis with nasal polyps. Further investigations are mandatory considering EGPA patients at their initial diagnosis and before any treatment, in terms of nasal histology and blood inflammatory cells, to identify markers characterizing sinonasal mucosa inflammation and useful for an early diagnosis of EGPA.

Objectives: The aim of this study was to investigate if any clinical and phoniatric characteristics or quality-of-life measures could predict the outcome of unilateral vocal fold paralysis (UVFP) initially managed with speech therapy. Methods: Forty-six patients with UVFP were evaluated using laryngostroboscopy, the GIRBAS (grade, instability, roughness, breathiness, asthenia, and strain) scale, acoustic analysis, and the Voice Handicap Index-10 (VHI-10) questionnaire. Treatment was speech therapy according to a 3-phase protocol. The main outcome measure was incomplete vocal fold mobility 12 months after symptom onset. Univariate and multivariate modeling ( k-nearest neighbors model) were applied. Results: Fifteen patients had incomplete motion recovery 12 months after the onset of UVFP. On univariate analysis, time to diagnosis (0.01), global grade of dysphonia (0.018), jitter (0.01), shimmer (0.012), and VHI-10 score (0.006) were associated with the outcome of vocal fold paralysis. Using a k-nearest neighbors multivariate discriminating model, the best discrimination of UVFP outcome was achieved with 4 parameters: global grade of dysphonia 2 or 3, jitter > 2.46%, shimmer > 6.97%, and VHI-10 score > 13. The model’s misclassification rate for incomplete motion recovery was only 6%. The model showed sensitivity of 93% and specificity of 74%. Conclusions: Delayed diagnosis and speech therapy was associated with negative outcomes. Higher grade of dysphonia, jitter, shimmer, and VHI-10 score on initial phoniatric assessment may help clinicians in predicting the outcomes of UVFP patients.

Objectives: Research selectively investigating non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is lacking. The inflammatory patterns seen in non-eosinophilic CRSwNP are still poorly understood. The present study is the first to compare blood eosinophil, basophil, and neutrophil counts before/after surgery in patients with non-eosinophilic CRSwNP stratified by their clinical features. Methods: The study concerned 107 consecutive patients with histologically confirmed non-eosinophilic CRSwNP who underwent endoscopic sinus surgery (ESS). Results: Statistical analysis ruled out any significant change in mean blood eosinophil, basophil, and neutrophil counts after ESS. A significant positive correlation emerged between blood eosinophil and basophil counts in both pre- and post-ESS laboratory tests. In the subcohort of allergic patients, a significant negative correlation was found after ESS between eosinophil and neutrophil levels and between basophil and neutrophil levels. Conclusions: In eosinophilic CRSwNP, ESS can clear polyps, remove inflammatory tissue, and reduce the inflammatory cytokines it generates, with a consequent reduction in blood eosinophil levels. The different results in non-eosinophilic CRSwNP support the conviction that the 2 types of CRSwNP are entities with distinct inflammatory response patterns.

Deep neck infections (DNIs) are often clinically challenging, and may be life-threatening.The present retrospective study aimed to identify panels of clinical, laboratory, radiological, and microbiological parameters that could identify patients with DNIs at higher risk of complications or long-term hospitalization.The investigation concerned 301 consecutive patients with DNIs treated at our institution between 2000 and 2014.The discriminatory power of a combination of two variables (unknown origin of the infection and the need for surgical treatment) in terms of deep neck infection complications occurrence featured an AUC (ROC) of 0.6701. The power of a panel of four variables (age, leukocyte count, need for surgical treatment, days elapsing from hospitalization to surgical procedure) to identify DNIs necessitating long-term hospitalization featured an AUC (ROC) of 0.7929.Using the scale proposed by Hosmer and Lemeshow, the four-variable panel showed an amply acceptable, nearly excellent discriminatory power for long-term hospitalization.Although this panel achieved promising results for prognostic purposes, other parameters potentially capable of predicting the outcome of DNIs and orienting treatment decisions need to be investigated.

Background/Objective The main end point of this investigation was to review our experience gained from 2009 to 2015 of treating chronic rhinosinusitis with nasal polyps (CRSwNP) in elderly patients (≥65 years old) with functional endoscopic sinus surgery. Secondary aims were to analyze the prognostic variables for CRSwNP in elderly patients and to compare the demographic, clinical, laboratory, histologic, and prognostic characteristics of CRSwNP in elderly versus young adult patients (20-40 years old). Methods Forty-three consecutive elderly patients and 71 consecutive young adult patients with CRSwNP were enrolled. Results Significant associations were found in the elderly group between CRSwNP recurrence and allergy (p = 0.037), CRSwNP recurrence and asthma (p = 0.017), and CRSwNP recurrence and acetyl salicylic acid (ASA) intolerance (p = 0.032) but not between recurrence and eosinophilic/noneosinophilic CRSwNP histology. Significant associations emerged in the young adult group between CRSwNP recurrence and asthma (p = 0.009), and ASA intolerance (p = 0.016), and serum eosinophil count (p = 0.02). The recurrence rate was also significantly higher for young adult patients with eosinophilic-type CRSwNP (p = 0.001). CRSwNP recurred less often in the elderly than in the young adult patients (p = 0.05). Conclusion The present preliminary investigation found a lower recurrence rate after functional endoscopic sinus surgery for CRSwNP in elderly patients than in young adult patients. Further investigations on larger, prospective series are mandatory to support the hypothesis that, although eosinophilic-type CRSwNP is generally considered a variant at high risk of recurrence and that probably warrants stricter postoperative follow-up and adjuvant postoperative medical treatment, these considerations could not be applied to elderly patients.

Objectives/Hypothesis To retrospectively analyze our experience of transoral laser microsurgery (TLM) for treating postoperative laryngeal obstruction (POLO) after supracricoid and supratracheal laryngectomy (open partial horizontal laryngectomy [OPHL]) types 2 and 3, and to investigate potential relationships between patients' clinical features and their functional outcomes. Study Design A retrospective cohort study. Methods The prognostic influence of clinical and surgical parameters on functional outcomes was investigated in a univariate statistical setting in terms of decannulation rate (DR), time to tracheostomy closure (TTC), and number of laser procedures required (NLP). Results OPHL type 2 was associated with a better functional outcome than OPHL type 3 in terms of DR, TTC, and NLP (P = .03, P = .02, and P = .02, respectively). Annular and semicircumferential stenoses developed more frequently after OPHL type 3, and were particularly difficult to manage with TLM. Fixation of the residual arytenoid was a negative prognostic factor in terms of functional outcome in terms of DR, TTC, and NLP (P = .0002, P = .08, and P = .08, respectively). Conclusions There is no standardized laser treatment for POLO; it must be tailored to individual patients. Identifying prognostic factors influencing functional outcome could help surgeons to earmark patients less likely to benefit from TLM for the treatment of POLO, and enable an adequate preoperative counseling, given the high probability of repeat postoperative TLM procedures. Level of Evidence 4 Laryngoscope, 2016 127:359–365, 2017

Background Treatment for local glottic cancer recurrences after primary transoral laser microsurgery (TLM) has not been standardized. Methods In 33 consecutive cases of salvage TLM after laser surgery for early glottic carcinoma failed, we retrospectively considered the potential clinicopathological prognostic factors in univariate statistical setting. Results Patient age

Aim. To investigate the role of dental malocclusion treatment in the outcomes of Recurrent Acute Otitis Media (RAOM). Materials and Methods. The clinical outcome (number of acute recurrences in 12 months) of 61 consecutive children treated medically for RAOM was analysed. Children underwent an odontostomatologic evaluation, a fiberoptic endoscopy, and skin-prick tests. Results. 32 children (group A) were diagnosed with dental malocclusion and treated with a mandibular repositioning plate. Dental malocclusion was ruled out in the other 29 patients with RAOM, and they were used as controls (group B). The two groups were homogeneous in terms of sex, exposure to RAOM risk factors, skin test results, and adenoid hypertrophy, while age was significantly higher in group A. Age, sex, exposure to RAOM risk factors, adenoid hypertrophy, and skin test results were not associated with RAOM outcome. Children in group A treated for dental malocclusion were strongly associated with a lower number of acute episode recurrences at both univariate (p<0.0001) and multivariate analysis (p=0.001). Conclusions. RAOM showed better outcomes in children with dental malocclusion wearing a mandibular repositioning device. Dental malocclusion in children with RAOM may play a role in the pathogenesis of Eustachian tube dysfunction.

Purpose The main aim of the study was to preliminarily investigate the possibly related role of nuclear onco-suppressors maspin and nm23-H1, a metastasis suppressor, in laryngeal squamous cell carcinoma (LSCC). Materials and methods Maspin expression pattern and nuclear nm23-H1 expression were ascertained in 62 consecutive LSCCs. Results Recurrence rate was significantly lower in patients with a nuclear maspin pattern of expression; nuclear nm23-H1 expression was significantly lower in patients who experienced disease recurrence. Disease free survival (DFS) was significantly longer in patients with maspin nuclear pattern or with nuclear nm23-H1 expression ≥10%. A significant association was found between nuclear nm23-H1 expression and maspin pattern of expression in LSCC. KNN discriminant analysis considered N status, maspin sub-cellular localization and nuclear nm23-H1 expression. The selected variables' accuracy in terms of relapse was 82%. Positive predictive accuracy was 100%, and negative predictive accuracy 79%. Conclusions Nuclear nm23-H1 expression and maspin pattern, also in association, show promise as recurrence indicators in LSCC. Further studies are needed to shed more light on the nm23-H1 mechanism of action in LSCC and thus find ways to restore nm23-H1 loss. These preliminary findings suggest that re-activating maspin functions might represent an important goal in the treatment of advanced LSCC.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Prognosis is poor, and therapeutic options are limited. MicroRNAs (miRNAs) have emerged as potential therapeutic molecules against cancer. Here, we investigated the therapeutic efficacy of miR-199a-3p, an miRNA highly expressed in normal liver and downregulated in virtually all HCCs. The therapeutic value of miR-199a-3p mimic molecules was assayed in the TG221 mouse, a transgenic model highly predisposed to the development of liver cancer. Administration of miR-199a-3p mimics in the TG221 transgenic mouse showing liver cancer led to a significant reduction of number and size of tumor nodules compared to control animals. In vivo delivery confirmed protein downregulation of the miR-199a-3p direct targets, mechanistic target of rapamycin (MTOR) and p21 activated kinase 4 (PAK4), ultimately leading to the repression of FOXM1. Remarkably, the anti-tumor activity of miR-199a-3p mimics was comparable to that obtained with sorafenib. These results suggested that miR-199a-3p may be considered a promising HCC therapeutic option.

Background: Sinonasal inverted (schneiderian) papilloma (IP) is histologically benign but shows a propensity for malignant transformation. Survivin, a member of the inhibitor of the apoptosis family of proteins that controls cell division, apoptosis, metastasis, and, probably, also neoangiogenesis, is overexpressed in essentially all human cancers. Overexpression of the multidomain protein cortactin has also been associated with increased cell migration, invasion, and metastatic potential in several malignancies. Objective: The aim of the present study was to preliminarily investigate survivin and cortactin expression in a consecutive series of sinonasal IPs, and IP-associated squamous cell carcinomas (SCC). Methods: Immunohistochemical expression of nuclear survivin and cortactin was measured in 19 consecutive sinonasal IPs and 3 IP-associated SCCs. Results: The mean ± standard deviation nuclear survivin expression was 9.4 ± 9.2% and 31.7% ± 15.4% in sinonasal IPs and SCCs, respectively (p < 0.0001). Results of cortactin immunostaining was strongly positive in the cytoplasm of both sinonasal IPs and SCCs: no significant difference emerged between the IP and SCC epithelial components. Conclusion: Nuclear survivin expression was significantly higher in SCCs than in IPs. Prospective, multi-institutional prognostic studies, preferably on an international scale (given the few cases treated at single institutions), are needed to confirm the role of survivin in IP malignant transformation.

Background: The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility. The present study focused mainly on the role of cortactin and phosphorylated cortactin (residues tyr421 and tyr466) expression and subcellular localization in primary supraglottic LSCCs and their cervical lymph node metastases. Methods: The immunohistochemical expression of cortactin, p-Y466-cortactin and p-Y421-cortactin was assessed in 38 primary supraglottic LSCCs and 10 lymph node metastases. The statistical approach included bootstrapping analysis. Results: Despite a significantly higher expression of cortactin in carcinoma cells than in adjacent normal laryngeal mucosa, no associations emerged between prognosis and the expression of cortactin or its isoforms in supraglottic LSCC. Statistical analysis found cortactin expression higher in less-differentiated LSCCs (p = 0.03). A significant direct correlation was found between cortactin and p-Y466-cortactin levels (p = 0.031), and between p-Y466-cortactin and p-Y421-cortactin levels (p = 0.001). Conclusions: Cortactin expression in carcinoma cells and its known involvement in the EGFR pathway suggest a role for this protein as a target for LSCC therapy. Further prospective studies are needed to investigate the potential of cortactin, p-Y466-cortactin and p-Y421-cortactin expression as markers of response to treatment (particularly EGFR-directed agents) in LSCC.

Background Most authors agree that radical surgery for advanced, aggressive temporal bone squamous cell carcinoma (SCC) should be followed by postoperative radiotherapy (PORT). The purpose of this study was to identify clinical and/or conventional pathological parameters capable of pinpointing patients with temporal bone SCC at higher risk of recurrence after PORT. Methods The investigation concerned 27 consecutive patients undergoing PORT for primary temporal bone SCC. Results Univariate statistics revealed a difference in the distributions for pT classification (p = .0004), pathological grade (p = .006), and dura mater involvement (p = .015) when patients were grouped by presence versus absence of recurrence after PORT. A panel of 3 parameters comprising pT classification (pT4), pathological grade (G2 or G3), and dura mater involvement demonstrated an outstanding discriminatory power (area under the curve [AUC] receiver operating characteristic [ROC] = 0.912) in predicting temporal bone SCC recurrence after PORT. Conclusion The panel considered had an outstanding discriminatory power in pinpointing patients at higher risk of recurrence who could benefit from stricter follow-up protocols and postoperative chemoradiotherapy (CRT) for temporal bone SCC. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

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.

Background Our primary endpoint was to use nasal cytology to compare woodworkers with unexposed subjects to see if wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary endpoint was to identify any differences in the exposed group's nasal symptoms or nasal cytology by years of exposure or personal exposure levels. Methods Ninety-two woodworkers and 90 controls were assessed using a questionnaire and nasal cytology (on nasal mucosa obtained by scraping). Wood dust exposure was investigated using personal sampling methods. Results Woodworkers reported significantly more nasal symptoms than controls (p < 0.00001). The woodworkers' nasal smears revealed more neutrophils (p = 0.001) and significantly higher mean neutrophil scores (p = 0.001) than control smears. Lymphocytes were also found more often in the woodworkers' rhinocytograms (statistical trend, p = 0.06). Neutrophilic rhinitis was diagnosed more frequently in the exposed workers than in controls (chi-square = 5.97, p < 0.05). Woodworkers with lymphocytes in their nasal smears had been exposed to wood dust for longer periods of time (statistical trend; p = 0.06). No differences in nasal symptoms or cell counts emerged when woodworkers were stratified by levels of personal exposure. Conclusion Nasal cytology should be further investigated in woodworkers before considering it a screening method for identifying woodworkers with chronic inflammatory rhinitis.

Purpose Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a significant recurrence rate. We reviewed our experience with recurrent TBSCCs. Materials and methods Clinicopathological and therapeutic variables potentially associated with disease-free survival (DFS) and disease-specific survival (DSS) were assessed in 17 TBSCC patients who died of their disease after treatment. Results TBSCC recurrences were treated with surgery in 12 cases (palliative in 11, with curative intent in 1) and palliative chemotherapy in 5; the median DFS and DSS were 6 and 16 months, respectively. The mean DFS and DSS were longer in patients who had primary lateral temporal bone resection (LTBR) rather than subtotal temporal bone resection (STBR) (p = 0.0173 and p = 0.03, respectively). Patients given non-surgical palliative treatment for recurrences had a longer mean DSS than those who underwent surgery (trend toward significance, p = 0.09). Conclusions Our results reflect the aggressive nature of TBSCC recurrences. Our findings seem to support the use of non-surgical treatments (chemotherapy, radiotherapy, or specialist palliative care) in patients with loco-regionally advanced recurrent TBSCC. Salvage surgery might be considered for early recurrences when radicality is still achievable. Precise guidelines for the rational follow-up of surgically-treated TBSCCs need to be shared between tertiary centers.

BACKGROUND In epithelial-to-mesenchymal transition, epithelial cells lose their features, acquiring a mesenchymal-like phenotype. Nm23-H1 protein relates to tumor cells' metastatic potential, its low expression in carcinomas often meaning a poor prognosis. This study newly investigated the role of nuclear nm23-H1 in laryngeal squamous cell carcinoma epithelial-to-mesenchymal transition. METHODS Immunohistochemical analyses of nuclear nm23-H1, E-cadherin, N-cadherin, Snail, Zinc finger E-box binding homeobox (ZEB)1, and ZEB2 were performed in 33 consecutive patients with laryngeal SCC. RESULTS Mean nuclear nm23-H1 expression was lower in patients whose disease recurred (P = .0046). Disease-free survival (DFS) was longer for patients whose nuclear nm23-H1 expression was ≥10% (P = .0083). Nuclear nm23-H1 and E-cadherin expressions correlated directly (P = .018). Mean E-cadherin expression was lower in patients whose disease recurred (P = .03). The DFS was shorter in patients with ZEB2 expression ≥5% (P = .006). CONCLUSIONS Nuclear nm23-H1 expression warrants further investigation in laryngeal SCC as a prognostic marker identifying patients at higher risk of recurrence. nm23-H1 targeted treatments may be capable of regulating epithelial-to-mesenchymal transition.

The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility. The present study focused mainly on the role of cortactin and phosphorylated cortactin (residues tyrThe immunohistochemical expression of cortactin, p-Y466-cortactin and p-Y421-cortactin was assessed in 38 primary supraglottic LSCCs and 10 lymph node metastases. The statistical approach included bootstrapping analysis.Despite a significantly higher expression of cortactin in carcinoma cells than in adjacent normal laryngeal mucosa, no associations emerged between prognosis and the expression of cortactin or its isoforms in supraglottic LSCC. Statistical analysis found cortactin expression higher in less-differentiated LSCCs (p = 0.03). A significant direct correlation was found between cortactin and p-Y466-cortactin levels (p = 0.031), and between p-Y466-cortactin and p-Y421-cortactin levels (p = 0.001).Cortactin expression in carcinoma cells and its known involvement in the EGFR pathway suggest a role for this protein as a target for LSCC therapy. Further prospective studies are needed to investigate the potential of cortactin, p-Y466-cortactin and p-Y421-cortactin expression as markers of response to treatment (particularly EGFR-directed agents) in LSCC.

In a recent preliminary study, eosinophil and basophil counts were calculated in chronic rhinosinusitis with nasal polyps (CRSwNP) using conventional histologic and immunohistochemical methods. The tissue eosinophil-to-basophil ratio differed in the CRSwNP endotypes considered.To compare the blood eosinophil-to-basophil ratio (bEBR) in a large series of patients with CRSwNP with that in a control group of consecutive rhinological patients with no evidence of nasal, paranasal, or systemic inflammatory disorders.A retrospective study was performed on 334 patients with CRSwNP to compare the preoperative bEBR among different endotypes and with controls (69 cases).The mean bEBR was significantly higher in the CRSwNP group than in the control group (P = .0006). The eosinophil and basophil counts were significantly and directly correlated in the CRSwNP cases (P = .0000). The mean bEBR was significantly higher in the sub-cohorts of CRSwNP with allergy (P = .0007), asthma (P = .0000), and aspirin-exacerbated respiratory disease (P = .0153). The mean bEBR was significantly higher in the sub-cohort with eosinophilic CRSwNP than in the sub-cohort with noneosinophilic CRSwNP (P = .0000).This study confirms the increasingly interesting role emerging for blood eosinophils and basophils in different CRSwNP endotypes. The bEBR seems to be a parameter worth investigating in different CRSwNP endotypes, because it is significantly higher in patients with allergy, asthma, and aspirin-exacerbated respiratory disease.

Background Although the diagnosis and treatment of eighth cranial nerve (VIII CN) schwannoma (acoustic neuroma) has improved over the years, no factors capable of predicting tumor growth have been identified as yet. This study is a preliminary investigation of the expression in sporadic VIII CN schwannomas of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), and amphiregulin (AREG), a direct target gene of YAP and TAZ. The expression of YAP, TAZ and AREG was correlated with the volumetric dimensions of tumors on contrast-enhanced magnetic resonance imaging (ceMRI). Methods YAP, TAZ and AREG expression was assessed immunohistochemically in surgical specimens of 36 consecutive sporadic VIII CN schwannomas. 3D reconstructions of the tumors and their corresponding volumes in cm3 were obtained from measurements on ceMRI images using the OsiriX® software. Results We found a significant direct correlation between TAZ expression and VIII CN schwannoma volumes on latest preoperative ceMRI (p3 than in those with a volume 3 (pConclusions The immunohistochemical expression of TAZ (but not YAP or AREG) correlated significantly with schwannoma volume measured on ceMRI. Further investigations are needed to identify the biological factors influencing tumor proliferation (ideally secreted proteins like AREG) that might be detected using non-invasive approaches (i.e., blood samples).

Purpose Cortactin is a multidomain protein engaged in several cellular mechanisms involving actin assembly and cytoskeletal arrangement. Cortactin overexpression in several malignancies has been associated with increased cell migration, invasion, and metastatic potential. Cortactin needs to be activated by tyrosine or serine/threonine phosphorylation. The role of cortactin and phosphorylated cortactin (residue tyr 466 ) was investigated in temporal bone squamous cell carcinoma (TBSCC). Materials and methods Immunohistochemical expression of cortactin and phosphorylated cortactin (residue tyr 466 ) was assessed in 27 consecutively-operated TBSCCs. Results Several clinicopathological variables correlated with recurrence (pT stage, dura mater involvement), and disease-free survival (DFS) (cT stage, pT stage, pN status, dura mater involvement). Twenty-three of 24 immunohistochemically evaluable TBSCCs were cortactin-positive. Median cortactin expression was 75.0%. Cortactin reaction in the cytoplasm was more intense in carcinoma cells than in normal adjacent tissue. Recurrence and DFS rates did not correlate with cortactin and phosphorylated cortactin (residue tyr 466 ) expression in TBSCC specimens. Conclusions Cortactin upregulation in TBSCC supports the conviction that inhibiting cortactin functions could have selective effects on this malignancy. Multi-institutional studies should further investigate the role of cortactin and phosphorylated cortactin in TBSCC, and their potential clinical application in integrated treatment modalities.

Objectives Postoperative radiotherapy (PORT) improves locoregional control and survival rates for patients with advanced laryngeal carcinoma (LSCC), but reported outcomes after PORT for LSCC vary considerably. Predictive markers (including biomarkers) are needed for LSCC to orient the choice of the most appropriate adjuvant therapy for individual patients. The aim of this study was to identify a panel of LSCC tissue markers (considering EGFR, mTOR, survivin, Bcl-2, angiogenin, endoglin [CD105], nm23-H1) capable of pinpointing patients at higher risk of recurrence among 33 LSCC cases treated with PORT. Methods/Results Univariate analysis found 4 biomarkers (mTOR, nuclear survivin, CD105, non-nuclear nm23-H1) significantly associated with LSCC recurrence. A collinearity emerged between mTOR and CD105 expressions. The predictive role of two different panels (panel 1: mTOR, nuclear survivin, non-nuclear nm23-H1; panel 2: CD105, nuclear survivin, non-nuclear nm23-H1) was considered. According to the Hosmer and Lemeshow scale, panel 1 demonstrated an outstanding discriminatory power (AUC 0.903) in predicting LSCC recurrence after PORT. Panel 2 had an excellent discriminatory power too (AUC 0.899). Conclusions Both panels of biomarkers showed an important discriminatory power in pinpointing patients at higher risk of recurrence after PORT for LSCC who could reasonably benefit from adjuvant postoperative chemo-RT.

Objective: With an estimated incidence of 77 new cases per 100,000 population aged 65 years or above, idiopathic sudden sensorineural hearing loss (ISSNHL) is a common clinical finding in elderly patients. 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 consecutive elderly patients with ISSNHL. Study design: This investigation considered 49 consecutive elderly patients (≥ 65 years of age) treated for ISSNHL. Clinical parameters (signs, symptoms, comorbidities and treatments) and audiometric data were analysed using univariate and multivariate statistical approaches for prognostic purposes, i.e. to identify any correlation with hearing recovery, expressed according to Wilson's criteria. Results/Conclusions: No clinical signs and symptoms, and no specific therapeutic approac...

Background Combining primary surgery with postoperative radiotherapy (RT) significantly reduces locoregional recurrence rates in selected patients with laryngeal squamous cell carcinoma (SCC). A prognostic model was used to see if associating laryngeal SCC tissue markers (mammary serine protease inhibitor [MASPIN], CD105, angiogenin [ANG], and nm23-H1) with conventional criteria could better discriminate higher-risk patients warranting postoperative RT. Methods The study involved 76 consecutively operated patients with laryngeal SCC not recommended for postoperative RT, in accord with current guidelines. Results On multivariate statistical modeling, non-nuclear MASPIN expression (p = .022), a CD105 expression ≥5.28% in vascular endothelial cells (p = .003), an nm23-H1 nuclear expression in carcinoma cells ≤12.0% (p = .028), and an ANG expression ≥5.0% (p = .07, statistical trend) showed a negative prognostic significance. The discriminatory power for disease recurrence of the 4 considered biomarkers generated an area under the curve (AUC; receiver operating characteristic [ROC]) of 0.872. The Hosmer–Lemeshow scale indicated an excellent discriminatory power. Conclusion This panel's ability to predict laryngeal SCC recurrence warrants further prospective, randomized studies to assess its use among the parameters routinely considered before recommending postoperative RT for patients with laryngeal SCC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1534–1540, 2014

Objectives/Hypothesis Temporal bone squamous cell carcinoma (SCC) is an uncommon malignancy accounting for less than 0.2% of head and neck cancers. Despite advances in its early diagnosis, skull base microsurgery, radiotherapy, and integrated treatments, prognosis in advanced SCCs remains dismal. The present study aimed to analyze the clinicopathological variables potentially influencing outcome in a series of temporal bone SCCs. Study Design The prognosis of 41 patients with temporal bone SCC was assessed retrospectively using univariate and multivariate statistical approaches. Patients and Methods Twenty-two women and 19 men consecutively operated for primary temporal bone SCC with a curative intent at a tertiary referral center between 1980 and 2008. Results On univariate analysis, cT stage correlated with disease-free survival in months (DFS) (P = 0.037), and pT stage correlated with recurrence rate (P = 0.038), DFS (P = 0.013), and disease-specific survival (DSS) (P = 0.025). Lymph node status (cN0 or pN0 vs. pN+) was associated with DFS (P = 0.025). SCC grading correlated significantly with recurrence rate (P = 0.005), DFS (P = 0.004), and DSS (P = 0.0036). Dura mater involvement was significantly associated with a higher recurrence rate (P = 0.001), a shorter DFS (P = 0.00001), and a lower DSS (P = 0.0001). On multivariate analysis, only dura mater involvement (P = 0.001) and N status (P = 0.012) remained independently prognostic of DFS. Conclusion Recurrences occurred despite obtaining block resections according to the tumor's clinical stage and pathologically free margins in all cases. Further analyses are mandatory to investigate hidden microscopic pathways of tumor diffusion, particularly in bone. Multi-institutional protocols are needed to facilitate comparisons between studies and enable meaningful meta-analyses. Level of Evidence 2b. Laryngoscope, 124:1192–1198, 2014

Temporal bone squamous cell carcinoma (SCC) accounts for less than 0.2% of all head and neck tumors. Although some progress has been made in treating this aggressive tumor, the prognosis in advanced cases remains poor. More effective therapeutic strategies need to be considered, including receptor-mediated carcinoma-targeted therapy. Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti-apoptosis, invasion, angiogenesis, and immune surveillance evasion. The aim of the present study was to preliminarily investigate the potential prognostic role of pSTAT3 expression in temporal bone SCC.Retrospective clinicopathologic investigation.Tertiary referral centers.Twenty-five consecutively operated patients with primary temporal bone SCC.pSTAT3 immunohistochemical expression in primary temporal bone SCCs was assessed with the aid of computer-based image analysis.Conventional clinicopathologic parameters and pSTAT3 expression were correlated with SCC prognosis.pT, stage, and surgical margin status were significantly related with recurrence rate (p = 0.002, p = 0.01, and p = 0.047, respectively) and disease-free survival (DFS) (p = 0.0049, p = 0.031, and p = 0.035, respectively). pT classification was also related with disease-specific survival (DSS) (p = 0.035). The SCC recurrence rate did not correlate with pSTAT3 expression. Statistical analyses ruled out any significant difference in DFS or DSS when patients were stratified by pSTAT3 expression (80.0% or ≤80.0%).Despite our preliminary results, the role of pSTAT3 in temporal bone SCC warrants further investigation in larger series because there is increasing evidence in preclinical models to indicate that inhibiting STAT3 phosphorylation can be a useful addition to different anticancer strategies.

Nuclear nm23-H1 expression may be useful in identifying elderly patients operated for laryngeal squamous cell carcinoma (LSCC) at higher risk of recurrence. Further studies are needed to clarify the biological role of nm23-H1 in elderly patients with LSCC and to determine how to restore nm23-H1 loss of expression/function.Nowadays more than 50% of cancer cases are elderly patients and this percentage is expected to be 70% by 2030. Despite advances in LSCC diagnosis and treatment, patient survival has not improved in the last two decades. Novel, effective strategies should rely also on receptor-mediated LSCC-targeted therapy. nm23-H1 protein is related to the tumor cells' metastatic potential, and low nm23-H1 expression in carcinomas often correlates with a poor prognosis.Immunohistochemistry and image analysis were used to investigate the prognostic value of nm23-H1 expression and subcellular localization in a series of 54 elderly patients consecutively undergoing primary surgery for LSCC.On univariate analysis, the disease recurrence rate correlated inversely with nuclear nm23-H1 expression (p = 0.014), and disease-free survival (DFS) was longer in patients whose nuclear nm23-H1 levels were ≥2.0% (p = 0.022). On multivariate analysis, nuclear nm23-H1 expression (hazard ratio (HR) 2.77, p = 0.022) and N stage (HR 3.49, p = 0.007) were prognostically significant in terms of DFS.

Purpose: To investigate the presence of KIT gene mutations and immunoreactivity in 85 conjunctival melanocytic tumours and to clarify the role of KIT as a potential therapeutic target in this group of patients. Methods: Eighty-five conjunctival pigmented tumours [27 melanomas, 12 primary acquired melanosis (PAMs) and 46 nevi] were immunostained for KIT. Intensity and pattern of expression were evaluated. Molecular analysis to identify KIT mutations was performed in 15 selected cases (tumour-rich areas >50%). KIT immunostaining score and pattern were statistically related to patients’ age, sex, diagnostic category, presence of relapse, disease-free survival, presence of metastases, metastasis-free survival, limbal versus nonlimbal tumour location and thickness of melanomas. Results: KIT stains were documented in 48% of melanomas, 50% of PAMs and 24% of nevi. The mean score of KIT staining in the melanomas/PAMs group was significantly different from nevi (p = 0.0076). No statistically significant differences were detected between either c-kit immunostaining score or pattern and each of the other clinico-pathologic parameters considered. No KIT gene mutations were detected in melanomas and nevi. A silent mutation/polymorphism in KIT exon 13 was found in one PAM. Conclusions: Despite the high level of KIT immunostains in PAMs and melanomas, this parameter seems not to be a good predictor of the presence of molecular mutations. KIT-activating mutations should be considered an uncommon event in this tumour.

Cortactin is a multidomain protein engaged in several cellular mechanisms involving actin assembly and cytoskeletal arrangement. Cortactin overexpression in several malignancies has been associated with increased cell migration, invasion, and metastatic potential. Cortactin needs to be activated by tyrosine or serine/threonine phosphorylation. The role of cortactin and phosphorylated cortactin (residue tyrImmunohistochemical expression of cortactin and phosphorylated cortactin (residue tyrSeveral clinicopathological variables correlated with recurrence (pT stage, dura mater involvement), and disease-free survival (DFS) (cT stage, pT stage, pN status, dura mater involvement). Twenty-three of 24 immunohistochemically evaluable TBSCCs were cortactin-positive. Median cortactin expression was 75.0%. Cortactin reaction in the cytoplasm was more intense in carcinoma cells than in normal adjacent tissue. Recurrence and DFS rates did not correlate with cortactin and phosphorylated cortactin (residue tyrCortactin upregulation in TBSCC supports the conviction that inhibiting cortactin functions could have selective effects on this malignancy. Multi-institutional studies should further investigate the role of cortactin and phosphorylated cortactin in TBSCC, and their potential clinical application in integrated treatment modalities.

AimsSurvivin—a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis—is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent findings also correlate survivin expression with the regulation of angiogenesis. The novel main aim of this study was a preliminary investigation into the potential role of survivin expression in LSCC neoangiogenesis, as determined by endoglin-assessed microvascular density (MVD).MethodsImmunohistochemical expression of nuclear survivin and endoglin-assessed MVD were ascertained by image analysis in 75 consecutive LSCCs.ResultsStatistical analysis disclosed a strong direct correlation between nuclear survivin expression and MVD. Patients whose nuclear survivin expression was ≥6.0% had a significantly higher LSCC recurrence rate, and a significantly shorter disease-free survival (DFS) than those with a nuclear survivin expression ConclusionsSurvivin-targeting strategies to enhance tumour cell response to apoptosis and inhibit tumour growth should receive more attention with a view to developing agents for use in multimodality advanced LSCC treatment, or combined with conventional chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting should also be further investigated for anti-angiogenic purposes, to reduce tumour blood flow and induce cancer necrosis.

Purpose Despite advances in the diagnosis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), their recurrence rate remains significant. There is a need for promptly-obtainable, inexpensive, minimally-invasive prognostic parameters to enable rhinologists to identify patients at higher risk of recurrent CRSwNP. The prognostic role of the neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR), previously discussed as potential markers of inflammation, has already been investigated in CRSwNP. The aim of the present study was to test the prognostic value of the NLR and ELR, and also of the basophil-to-lymphocyte ratio (BLR) (given the emerging role of basophils in CRSwNP) in a large series of CRSwNP. Materials and methods The study concerned 240 patients who underwent FESS for CRSwNP from 2009 to 2014 and had a postoperative follow-up longer than 12 months. We considered patients with recurrences as those with endoscopic evidence of at least grade I polyposis. Results In our series, the mean NLR, ELR and BLR were significantly higher in patients whose disease recurred than in those remaining recurrence-free (p = 0.03, p = 0.0001, and p = 0.0002, respectively), but the discriminatory power of the NLR, ELR, or BLR in terms of disease recurrence was unacceptable (AUCs = 0.600, 0.678, and 0.662, respectively). Conclusions The heterogeneous prognostic role of NLR, ELR and BLR identified in the clinically and pathologically different sub-cohorts of CRSwNP considered supports the hypothesis that CRSwNPs with a similar clinical picture may differ considerably in terms of the biological and pathogenic mechanisms of polyp formation and growth.

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