Primary temporal bone squamous cell carcinoma: Comparing the prognostic value of the American Joint Committee on Cancer TNM classification (8th edition) with the revised Pittsburgh staging system.

BACKGROUND: Retrospectively considering a temporal bone squamous cell carcinomas (TBSCCs) series, our aim was to compare the predictive power of the American Joint Committee on Cancer (AJCC) staging system (8th edition) with the revised Pittsburgh staging system (rPSS) in terms of disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). METHODS: Forty-three TBSCCs consecutively treated surgically were reviewed. The prognostic performance of AJCC and rPSS was compared. RESULTS: The areas under the curves for the prediction of DFS, DSS, and OS did not differ significantly between both staging systems (p = 0.518, p = 0.940, and p = 0.910, respectively). Harrel's C-indexes for respectively the AJCC and rPSS were 0.76 and 0.70 for DFS, 0.73 and 0.76 for DSS, 0.66 and 0.63 for OS. CONCLUSION: Comparable prognostic accuracy was observed between AJCC and rPSS. Levels of prognostic performance were only acceptable for both systems, according to Hosmer-Lemeshow scale. Further efforts are needed to define new TBSCC staging modalities with higher prognostic reliability.

Cochlear implant in vestibular schwannomas: long-term outcomes and critical analysis of indications.

PURPOSE: To describe our institutional experience in cochlear implantation after vestibular schwannoma (VS) resection, and compare the audiological outcomes between sporadic and neurofibromatosis type 2 (NF2) VS sub-cohorts of patients, and in relation to preoperative contralateral hearing. METHODS: Seventeen patients (8 sporadic and 9 NF2-associated VSs) who had undergone VS resection and cochlear implant (CI) were analyzed retrospectively. Audiological outcomes at 24 months were correlated with preoperative clinical variables. The results according to VS type (sporadic vs. NF2-associated) and contralateral hearing (impaired vs. normal) were compared. RESULTS: Fourteen CIs were actively used by the patients (77.8%). Twenty-four months after CI activation, the median postoperative PTA (pure tone average) was 45.6 dB nHL and a measurable WRS (Word Recognition Score) was achieved by 44.4% of patients (median WRS = 40%). The median postoperative PTA in the implanted ear resulted better in the group with an impaired contralateral hearing (36.3 dB nHL vs. 78.8 dB nHL, p = 0.019). Good preoperative contralateral hearing status (A-B classes of AAO-HNS) was a negative prognostic factor for CI performance on open-set discrimination (OR = 28.0, 95% CI 2.07-379.25, p = 0.012). CONCLUSIONS: CI is a viable rehabilitative option for patients with sporadic or NF2-associated VS. A good contralateral hearing adversely affects CI outcome and should be taken into consideration for patients' selection and rehabilitation programs.

Pediatric Hearing Loss Management in the COVID-19 Era: Possible Consequences and Resources for the Next Future.

Pediatric hearing loss early diagnosis and treatment have been limited by the current restrictions due to the coronavirus disease 2019 pandemic. The difficulty in accessing the multiple facilities required for the rehabilitative process is influencing the timing of each step of the process. Auditory hearing screening programs, etiological characterization, surgical timing, and speech therapies have all been limited in the past year. The current conditions have forced us to adopt different strategies to overcome the necessary social distancing prescriptions. Although their efficacy should be proved over time, some of these resources will be probably useful even in a nonpandemic future.

Temporal bone carcinoma: testing the prognostic value of a novel clinical and histological scoring system.

PURPOSE: Our group recently proposed the novel Padova prognostic scoring system for temporal bone carcinoma (TBSCC) that considers: the revised Pittsburgh staging system; radiological dura mater involvement; non-anterior spread (medial, inferior or posterior into the temporal bone and skull base) of T4 tumors; and histological grade. The aim of the present study was to validate this prognostic TBSCC scoring system in a case series selected from the literature. METHODS: A search was run to identify studies on TBSCC reporting the variables included in our score for each patient. Then our system was applied to the data extracted. RESULTS: Only two published investigations reported all the clinical and pathological data required for our scoring system. In one series from the Gruppo Otologico in Piacenza (Italy), a significantly higher recurrence rate (p = 0.008), shorter disease-free survival (DFS) (p = 0.001), higher disease-specific mortality (DSM) (p = 0.006), and shorter disease-specific survival (DSS) (p = 0.004) were associated with scores ≥ 5. Receiver operating curve (ROC) analysis showed an AUC of 0.804 for TBSCC recurrence, and 0.832 for DSM. In a series from Kyushu University Hospital (Japan), a significantly higher DSM (p = 0.018) and shorter DSS (p = 0.021) were associated with scores ≥ 5. ROC analysis showed an AUC of 0.812 for tumor relapse and 0.790 for DSM. CONCLUSION: Our TBSCC Padova scoring system confirmed its validity when applied to the only two international TBSCC series providing the required data. These preliminary results need to be confirmed in a multi-center prospective setting.

Age-independent increasing prevalence of Human Papillomavirus-driven oropharyngeal carcinomas in North-East Italy.

HPV-driven oropharyngeal carcinomas (OPCs) show geographical variations with increasing temporal trends in several areas. We investigated their frequency and clinical outcomes within a prospective multicenter cohort study in North-East Italy. A tumor was defined as HPV-driven by using at least two different biomarkers, usually HPV-DNA positivity and p16INK4A overexpression. Different survival outcomes were compared among patients with HPV-driven and non-HPV-driven tumors. Overall, 42/130 (32.3%) patients with newly diagnosed OPC during the period 2000-2018 resulted HPV-driven; HPV16 was involved in 37 cases (88%), HPV33 in 3 cases (7%), HPV58 and HPV18 in 1 case each. Over time, HPV-driven cases raised from 16.7% (6/36) during 2000-2006 to 46.1% (24/52) during 2013-2018 (p < 0.001). The increase in HPV-driven OPCs was more marked in females than males (p = 0.010), and the frequency of HPV-driven cases was similar in the different age groups. In comparison to cases with non-HPV-driven tumors, a significantly (p < 0.001) better progression-free and overall survival were recorded among patients affected by HPV-driven OPC. The prevalence of HPV-driven OPC cases has been significantly increasing during the last two decades also in North-East Italy and was associated with favorable outcome. OPCs driven by non-HPV16 oncogenic types were restricted to patients older than 68-yrs.

Cochlear implant outcomes in the elderly: a uni- and multivariate analyses of prognostic factors.

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.

Nuclear nonmetastatic protein 23-H1 expression and epithelial-mesenchymal transition in laryngeal carcinoma: A pilot investigation.

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.

Relaxin-2 expression in oral squamous cell carcinoma.

BACKGROUND: When advanced, oral squamous cell carcinoma (OSCC) may involve adjacent non-epithelial structures, and the prognosis is worse for bone invasion. Human relaxin-2 is a peptide hormone that has recently been associated with cancer. It can induce human osteoclast differentiation and activation, suggesting a role in tumor-driven osteolysis. This study was a preliminary assessment of the prognostic role of relaxin-2 in surgical specimens of OSCC tissue and adjacent but uninvolved mandibular/maxillary bone. METHODS: Relaxin-2 immunohistochemical expression and reaction intensity were assessed in tumor and uninvolved adjacent mandibular/maxillary bone specimens from 23 operated OSCC patients. RESULTS: All OSCC specimens were positive for relaxin-2. The intensity of its reaction in OSCC correlated significantly with the pattern of the tumor's invasion front (p = 0.02), being higher with the infiltrative pattern. Mean relaxin-2 immunohistochemical expression was higher in patients whose OSCC recurred after treatment than those experiencing no recurrence (81.3% ± 22.6% vs. 59.5% ± 29.7%, respectively). A significant direct association emerged between relaxin-2 expression in OSCC specimens and recurrence rate (p = 0.049). CONCLUSIONS: Relaxin-2 expression in OSCC should be further investigated as a potentially useful marker for identifying patients at higher risk of recurrence, who might benefit from closer follow-up and more aggressive adjuvant therapy. In other oncological settings, increasing evidence of relaxin being produced by cancer cells is prompting efforts to synthesize human relaxin-2 analogs capable of acting as antagonists and limiting tumor growth.

Combined Surgical Approach to Giant Cholesteatoma: A Case Report and Literature Review.

OBJECTIVES: Cholesteatomas can grow to a remarkable size before clinically making their presence felt. Managing giant cholesteatomas and their complications can become a challenge for the otological surgeon. METHODS: We describe a case of a giant congenital cholesteatoma of the mastoid in an adult. The lesion extended to the sigmoid sinus, jugular bulb, carotid canal, occipital condyle, and the lateral portion of the first cervical vertebra. Surgical excision was performed using a combined microscopic and endoscopic surgical approach. RESULTS: Our combined surgical technique enabled a more accurate removal of the cholesteatoma than a microscopic approach alone, with no surgical complications or damage to the structures affected by the disease. CONCLUSIONS: Using endoscopic instruments to manage giant cholesteatomas can help to avoid complications and improve surgical radicality.

Temporal bone carcinoma: a first glance beyond the conventional clinical and pathological prognostic factors.

Temporal bone squamous cell carcinoma (TBSCC) is an uncommon, aggressive malignancy with a poor prognosis in advanced cases. The dismal outcome is partially related to: the lack of reliable clinical or pathological prognostic factors and the largely unstandardized surgical and integrated treatments adopted. There is an undeniable need for novel diagnostic/therapeutic strategies to improve the prognosis. The purpose of this critical review was to explore the level of available knowledge concerning the molecular markers involved in the biology of TBSCC that have a prognostic potential. The Pub-Med and Scopus electronic databases were searched without publication date limits for studies investigating molecular markers in cohorts of patients with primary TBSCC. The search terms used were: "temporal bone cancer", "temporal bone carcinoma", "temporal bone malignancy", "ear cancer", "ear carcinoma", and "ear malignancy". We decided preliminarily not to consider series with less than five cases. Nine retrospective case series of TBSCC were found in which different analytical techniques had been used to study the role of several biomarkers (HPV, vimentin, transforming growth factor ß, CD105, RECK, matrix metalloproteinase-9, MASPIN, EBV, p16, TP53 mutation, pSTAT3, relaxin-2). CD105 expression (in tumor vessel endothelial cells) and MASPIN cytoplasmic expression (in carcinoma cells) were, respectively, found directly and inversely related with the neoplasm's recurrence rate. CD105 expression was also inversely related with disease-free survival in TBSCC. A future goal of such analyses should be to ascertain the radio- and chemo-sensitivity profiles of individual TBSCCs, enabling truly personalized therapies. A further, more ambitious goal will be to find targets for therapeutic agents that might prove crucial in improving the disease-specific survival for patients with advanced TBSCC.

Silver sucrose octasulfate nasal applications and wound healing after endoscopic sinus surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVES: The aim of the present prospective, randomized, double-blind, and placebo-controlled investigation (approved by the Ethical Committee of Padova University Hospital [Italy]) was to assess the effect of a nasal gel containing a combination of silver sucrose octasulfate and potassium sucrose octasulfate (Silsos gel® [SG]) in wound healing after endoscopic sinus surgery (ESS) for chronic rhinosinusitis in terms of: nasal symptoms (SNOT22), endoscopic appearance of the sinonasal mucosa (Lund-Kennedy score), nasal air flow (anterior active rhinomanometry), evidence of mucosal inflammatory processes (nasal cytology and histology), and microbiological growth. METHODS: Thirty-four patients with chronic rhinosinusitis were randomized on a 1:1 ratio to receive after ESS either SG or placebo (contained only the excipients [carbopol and propylene glycol] in the same concentrations as in SG). RESULTS/CONCLUSIONS: Judging from the present prospective investigation on patients who underwent ESS for chronic rhinosinusitis, treatment with SG seems to enable a significantly faster improvement in specific symptoms (assessed on the validated SNOT22 scale) than placebo. Patients treated with SG also had a quicker improvement in the endoscopic appearance of their nasal mucosa after ESS than patients treated with placebo. These endoscopic improvements in the SG group were also confirmed at the long-term follow-up, while the same did not apply to the placebo-treated group.

Endoglin (CD105) expression in sinonasal polyposis.

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.

Burkholderia cepacia complex isolation in non-polypoid chronic rhinosinusitis.

PURPOSE: Burkholderia cepacia complex (Bcc) infections of the head and neck have been infrequently reported in immunocompetent patients, while their association with cystic fibrosis is quite well known. One of the main problems associated with Bcc is their intrinsic resistance to most clinically-available antimicrobials. Bcc has already been isolated in sinonasal polyposis, while here we report for the first time on its isolation in patients with chronic rhinosinusitis (CRS) but no nasal polyposis. MATERIALS AND METHODS: Thirty-four consecutive surgically-treated CRS patients without cystic fibrosis were recruited. RESULTS: Bcc was isolated in 4 cases of CRS without polyposis, and in another case in sinonasal polyposis. All tested Bcc strains isolated in non-polypotic CRS were resistant to ciprofloxacin, amikacin, ertapenem, amoxicillin/clavulanate, cefotaxime, and gentamicin. CONCLUSIONS: The novel finding of Bcc species in CRS without polyposis as well suggests that the mechanism by which these bacteria adhere to the epithelium of the upper respiratory tract may be important in the host's colonization.

Multivariate approach to investigating prognostic factors in deep neck infections.

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.

Indications for postoperative radiotherapy in laryngeal carcinoma: a panel of tumor tissue markers for predicting locoregional recurrence in surgically treated carcinoma. A pilot study.

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.

A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative radiotherapy: an introductory investigation.

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.

Nm23-H1 nuclear expression is associated with a more favourable prognosis in laryngeal carcinoma: univariate and multivariate analysis.

AIMS: To use image analysis and multivariate analysis to investigate the prognostic significance of Nm23-H1 subcellular localization in a large cohort of laryngeal squamous cell carcinomas (LSCCs). METHODS AND RESULTS: Nm23-H1 total and nuclear levels were immunohistochemically determined and calculated with an image analysis system in 104 consecutively operated LSCCs. The mean follow-up was 58.3 ± 35.1 months (median 45 months). Total Nm23-H1 levels correlated only with patient stratification by pT (P=0.01). Mean nuclear Nm23-H1 levels were lower in patients with recurrent disease (P=0.01), and disease-free survival (DFS) was longer in patients whose nuclear levels of Nm23-H1 were >2.0% than in those with levels ≤ 2.0% (P=0.019). On multivariate analysis, Nm23-H1 nuclear expression [hazard ratio (HR) 2.59, P=0.005] and N stage (HR 3.60, P=0.0001) were prognostically significant in relation to DFS. CONCLUSIONS: In LSCC, Nm23-H1 nuclear expression may be useful for identifying patients at higher risk of recurrence after treatment and who might be considered for more aggressive therapy. Further investigations are needed before Nm23-H1 can be considered for use in targeted treatments for LSCC.

mTOR expression and prognosis in elderly patients with laryngeal carcinoma: uni- and multivariate analyses.

Cancer is common in the elderly, who may also be frail, which can complicate the choice of the best therapeutic approach. We sought to examine whether the serine-threonine kinase mTOR, a "master switch" in cancer cells that modulates metabolism, the cell cycle, and apoptosis, might help in clinical decision-making. The aim of the present study was thus to assess the potential prognostic role of mTOR in elderly patients with laryngeal carcinoma (LSCC). mTOR expression was determined immunohistochemically in 54 consecutive elderly (≥65 years old) patients with LSCC. On univariate analysis, nodal involvement and pathological stage correlated strongly with the elderly LSCC patients' prognosis in terms of disease recurrence rate and disease-free survival (DFS). Patients whose mTOR expression was >35.3% had a significantly higher recurrence rate (p=0.003) and shorter DFS (p=0.013). In the multivariate model, N status (p=0.001) and mTOR expression (p=0.026) maintained an independent prognostic significance in relation to DFS. mTOR probably influences the aggressive LSCC phenotype in elderly patients and its expression in elderly LSCC cases can be considered a prognostic marker potentially useful for identifying patients at higher risk of disease recurrence, and N0 patients at higher risk of recurrence who may benefit from more aggressive treatment. Since rapalogs (as mTOR inhibitors) might have an effect on LSCC, further investigations are needed to ascertain these agents' role in therapeutic strategies for advanced LSCC in elderly patients.