Post-traumatic Delayed Facial Nerve Palsy: Report of 2 Cases and Systematic Review.

OBJECTIVE: Delayed facial nerve palsy (dFNP) secondary to head injury is definitely uncommon. Although the mechanism of immediate facial nerve paralysis is well-studied, its delayed presentation remains debated. Given the dearth of available information, we reported herein our experience with 2 cases of posttraumatic dFNP. This systematic review aimed to evaluate all available information on dFNP and to assess treatment outcome also comparing conservatively and surgically approaches. DATA SOURCES: Pubmed, Scopus, and Web of Science databases were systematically screened. REVIEW METHODS: The protocol of this investigation was registered on PROSPERO in April 2023 and the systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. RESULTS: Both patients in the case studies showed a complete recovery within 2 to 3 months after the head trauma. One of them still reported a subjective taste alteration at last control. After the application of the inclusion-exclusion criteria, 9 manuscripts with adequate relevance to this topic were included in the systematic review. The study population consisted of 1971 patients with a diagnosis of posttraumatic facial nerve palsy, of which 128 with a dFNP. CONCLUSIONS: dFNP due to head trauma is a rarely encountered clinical entity, and optimal treatment still remains to be elucidated. Based on the reported data, it seems rational to propose a conservative approach for dFNP with steroid administration as a first line in most cases, indicating surgery in severe and/or refractory cases.

Spectro-acoustic voice parameters in transoral laser microsurgery vs exclusive radiotherapy for early-stage glottic carcinoma: A systematic review and meta-analysis.

PURPOSE: In early glottic squamous cell carcinoma, similar results have been described in terms of disease control between transoral laser microsurgery (TLM) and radiation therapy (RT). During the past two decades, several studies compared subjective vocal outcomes of exclusive RT with those of TLM, showing a trend towards improving results for TLM over time. However, the objective differences in terms of spectro-acoustic voice parameters between exclusive RT and TLM have been less frequently investigated. The aim of this systematic review with meta-analysis was to evaluate voice quality after TLM and RT treatment for early glottic carcinoma, based on acoustic analysis parameters including jitter, shimmer, noise to harmonic ratio, fundamental frequency and maximum phonation time. MATERIAL AND METHODS: A search of the English published literature was conducted on the Pubmed, Scopus and Cochrane databases following PRISMA guidelines. RESULTS: A total of 441 titles were retrieved from the search. After full-text screening and application of inclusion/exclusion criteria, 12 articles were included. We found no significant differences between TLM and RT treatment in the considered acoustic analysis parameters, except for Shimmer, with more favorable values reported in the RT group. CONCLUSIONS: Considering the spread of the disease and expecting an improvement in long-term survival over time, well-designed and multicentric studies involving larger populations with a long-term follow up are mandatory to better assess objective voice outcomes in terms of spectro-acoustic voice parameters.

Autosomal Recessive Non-Syndromic Deafness: Is AAV Gene Therapy a Real Chance?

The etiology of sensorineural hearing loss is heavily influenced by genetic mutations, with approximately 80% of cases attributed to genetic causes and only 20% to environmental factors. Over 100 non-syndromic deafness genes have been identified in humans thus far. In non-syndromic sensorineural hearing impairment, around 75-85% of cases follow an autosomal recessive inheritance pattern. In recent years, groundbreaking advancements in molecular gene therapy for inner-ear disorders have shown promising results. Experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome. These pioneering approaches have opened new possibilities for potential therapeutic interventions. Following the PRISMA criteria, we summarized the AAV gene therapy experiments showing hearing improvement in the preclinical phases of development in different animal models of DFNB deafness and the AAV gene therapy programs currently in clinical phases targeting autosomal recessive non syndromic hearing loss. A total of 17 preclinical studies and 3 clinical studies were found and listed. Despite the hurdles, there have been significant breakthroughs in the path of HL gene therapy, holding great potential for providing patients with novel and effective treatment.

Facial Surface Electromyography: A Novel Approach to Facial Nerve Functional Evaluation after Vestibular Schwannoma Surgery.

BACKGROUND: Vestibular schwannoma (VS) surgery may cause facial nerve damage. However, a comprehensive evaluation of post-operative facial outcomes may be difficult to achieve. Surface electromyography (sEMG) is a promising non-invasive evaluation tool. However, its use in the follow-up after VS surgery has not been reported yet. The main objective was to develop and validate a new sEMG application specifically for the post-VS surgery setting. Secondary goals were to provide a systematic description of facial muscle activity after VS surgery and assess the association between sEMG parameters and Sunnybrook scale scores. METHODS: Thirty-three patients with facial palsy following VS surgery were included. The clinical outcomes (Sunnybrook symmetry, movement, and synkinesis scores) and sEMG parameters (signal amplitude normalized by the maximal voluntary contraction (NEMG) and sEMG synkinesis score (ESS, number of synkinesis per movement sequence)) were evaluated at the end of the follow-up. RESULTS: In all tested muscles, NEMG variance was significantly higher on the affected side than the contralateral (variance ratio test, p < 0.00001 for each muscle). In total, 30 out of 33 patients (90.9%) showed an ESS ≥ 1 (median: 2.5, IQR: 1.5-3.0). On the affected side, NEMG values positively correlated with both dynamic and overall Sunnybrook scores (Spearman's model, p < 0.05 for each muscle, except orbicularis oculi). ESS significantly correlated with the Sunnybrook synkinesis score (Spearman's rho: 0.8268, p < 0.0001). CONCLUSIONS: We described and preliminarily validated a novel multiparametric sEMG approach based on both signal amplitude and synkinesis evaluation specifically for oto-neurosurgery. Large-scale studies are mandatory to further characterize the semiological and prognostic value of facial sEMG.

Implantable hearing devices in clinical practice. Systematic review and consensus statements.

Objective: Implantable hearing devices represent a modern and innovative solution for hearing restoration. Over the years, these high-tech devices have increasingly evolved but their use in clinical practice is not universally agreed in the scientific literature. Congresses, meetings, conferences, and consensus statements to achieve international agreement have been made. This work follows this line and aims to answer unsolved questions regarding examinations, selection criteria and surgery for implantable hearing devices. Materials and methods: A Consensus Working Group was established by the Italian Society of Otorhinolaryngology. A method group performed a systematic review for each single question to identify the current best evidence on the topic and to guide a multidisciplinary panel in developing the statements. Results: Twenty-nine consensus statements were approved by the Italian Society of Otorhinolaryngology. These were associated with 4 key area subtopics regarding pre-operative tests, otological, audiological and surgical indications. Conclusions: This consensus can be considered a further step forward to establish realistic guidelines on the debated topic of implantable hearing devices.

Cochlear implantation after head and neck radiotherapy: A multicentric study and systematic review.

OBJECTIVE: The objective of this study is to assess whether cochlear implantation is feasible in patients treated with radiotherapy of the temporal bone (for diseased other than vestibular schwannoma), in terms of surgical management and auditory outcome. METHODS: A systematic review of the literature was performed, screening PubMed, Embase, and Scopus databases, according to PRISMA criteria, retrieving 12 articles. Moreover, 9 cases coming from a multicentric study involving Padova and Pisa University Hospitals, were added, for a total of 62 cases of irradiated patients receiving cochlear implantation. RESULTS: In our multicentric study we included a total of 9 patients, 6 males, and 3 females (mean age at first cochlear implantation was 53.89 years ± 21.07), while from the literature we considered 53 cases (mean age at first cochlear implantation 48.78 years ± 12.41). We considered for both groups a set of preoperative imaging abnormalities, intraoperative complications and possible postoperative complications. In our cohort, the preoperative pure tone average (PTA) in the implanted ear was 105.6 dB, and the postoperative one was 34.6 dB. In the literature the preoperative PTA was 111.5 dB (when reported), and the postoperative one 52.8 dB. CONCLUSION: Both our experience and the literature suggest that cochlear implantation in an irradiated ear is feasible with a good auditory outcome. Surgical difficulties and fitting challenges can be easily managed by professionals aware of these findings, making these patients good candidates to this rehabilitative option.

Contemporary Perspectives in Pathophysiology of Facial Nerve Damage in Oto-Neurological and Skull Base Surgical Procedures: A Narrative Review.

During the last decades, neuro-otological surgery has progressively reduced functional morbidity, including facial nerve damage. However, the occurrence of this sequela may significantly impact on patients' quality of life. The aim of this narrative review is to provide an update on the patho-physiological and clinical issues related to facial nerve damage in oto-neurological and skull base surgery, in the light of a comprehensive therapeutic and rehabilitative approach to iatrogenic disfunctions. The narrative review is based on a search in the PubMed, Scopus, and Web of Science databases. In this surgical setting, the onset of intraoperative facial nerve damage is related to various aspects, mainly concerning the anatomical relationship between tumor and nerve, the trajectory of the surgical corridor, and the boundaries of the resection margins. Mechanisms related to stretching, compression, devascularization, and heating may play a role in determining intraoperative facial nerve damage and provide the patho-physiological basis for possible nerve regeneration disorders. Most of the studies included in this review, dealing with the pathophysiology of surgical facial nerve injury, were preclinical. Future research should focus on the association between intraoperative trauma mechanisms and their clinical correlates in surgical practice. Further investigations should also be conducted to collect and record intraoperative data on nerve damage mechanisms, as well as the reports from neuro-monitoring systems.

Assessing the accuracy of ChatGPT references in head and neck and ENT disciplines.

PURPOSE: ChatGPT has gained popularity as a web application since its release in 2022. While artificial intelligence (AI) systems' potential in scientific writing is widely discussed, their reliability in reviewing literature and providing accurate references remains unexplored. This study examines the reliability of references generated by ChatGPT language models in the Head and Neck field. METHODS: Twenty clinical questions were generated across different Head and Neck disciplines, to prompt ChatGPT versions 3.5 and 4.0 to produce texts on the assigned topics. The generated references were categorized as "true," "erroneous," or "inexistent" based on congruence with existing records in scientific databases. RESULTS: ChatGPT 4.0 outperformed version 3.5 in terms of reference reliability. However, both versions displayed a tendency to provide erroneous/non-existent references. CONCLUSIONS: It is crucial to address this challenge to maintain the reliability of scientific literature. Journals and institutions should establish strategies and good-practice principles in the evolving landscape of AI-assisted scientific writing.

Hearing Aid in Vestibular-Schwannoma-Related Hearing Loss: A Review.

(1) Background: Several types of hearing aids are available for the rehabilitation of vestibular-schwannoma (VS)-related hearing loss. There is a lack of recently published papers regarding this theme. The aim of the present work is to organize current knowledge. (2) Methods: A review of the literature regarding the topics "vestibular schwannoma", "hearing loss", and "hearing aid" was performed. Nineteen studies were thus considered. (3) Results: Conventional hearing aids, contralateral routing of signal (CROS) aids, bone anchored hearing aids (BAHA), and others are available options for hearing rehabilitation in VS patients. The speech discrimination score (SDS) is considered the best measure to assess candidacy for rehabilitation with hearing aids. The best hearing rehabilitative conditions in VS patients when using conventional hearing aid devices are a mild-moderate hearing loss degree with good word recognition (more than 50% SDS). CROS-Aid and BAHA are reported to be beneficial. CROS-Aid expands on the area of receiving hearing. BAHA aids use direct bone-conduction stimulation. Unfortunately, there are no available studies focused specifically on VS patients that compare CROS and BAHA technologies. (4) Conclusions: Hearing aids, CROS, and BAHA are viable options for rehabilitating hearing impairment in VS, but require an accurate case-by-case audiological evaluation for rehabilitating hearing impairment in VS. Further studies are needed to prove if what is currently known about similar hearing illnesses can be confirmed, particularly in the case of VS.

Vertebrobasilar and Basilar Dolichoectasia Causing Audio-Vestibular Manifestations: A Case Series with a Brief Literature Review.

Audio-vestibular symptoms can arise from vertebrobasilar dolichoectasia (VBD) and basilar dolichoectasia (BD). Given the dearth of available information, herein we reported our experience with different audio-vestibular disorders (AVDs) observed in a case series of VBD patients. Furthermore, a literature review analyzed the possible relationships between epidemiological, clinical, and neuroradiological findings and audiological prognosis. The electronic archive of our audiological tertiary referral center was screened. All identified patients had a diagnosis of VBD/BD according to Smoker's criteria and a comprehensive audiological evaluation. PubMed and Scopus databases were searched for inherent papers published from 1 January 2000 to 1 March 2023. Three subjects were found; all of them had high blood pressure, and only the patient with high-grade VBD showed progressive sensorineural hearing loss (SNHL). Seven original studies were retrieved from the literature, overall including 90 cases. AVDs were more common in males and present in late adulthood (mean age 65 years, range 37-71), with symptoms including progressive and sudden SNHL, tinnitus, and vertigo. Diagnosis was made using different audiological and vestibular tests and cerebral MRI. Management was hearing aid fitting and long-term follow-up, with only one case of microvascular decompression surgery. The mechanism by which VBD and BD can cause AVD is debated, with the main hypothesis being VIII cranial nerve compression and vascular impairment. Our reported cases suggested the possibility of central auditory dysfunction of retro-cochlear origin due to VBD, followed by rapidly progressing SNHL and/or unnoticed sudden SNHL. More research is needed to better understand this audiological entity and achieve an evidence-based effective treatment.

Digging into the Role of Inflammatory Biomarkers in Sudden Sensorineural Hearing Loss Diagnosis and Prognosis: A Systematic Review and Meta-Analysis.

Background and Objectives: Sudden Sensorineural Hearing Loss (SSNHL) is a quite common clinical finding in otolaryngology. Most cases are classified as idiopathic and there is a dearth of information on factors able to predict the response to treatment and hearing recovery. The main aim of this systematic review and meta-analysis was to assess and critically discuss the role of circulating inflammatory biomarkers in SSNHL. Materials and Methods: A search was conducted of the English literature published between 1 January 2009 and 7 July 2022 on Pubmed, Scopus, Web of Science, ScienceDirect, and Cochrane following PRISMA guidelines. Results: A total of 256 titles were retrieved from the search. After full-text screening and application of inclusion/exclusion criteria, 13 articles were included. Twelve out of thirteen studies reported significant differences in biomarkers values in SSNHL patients, of which Tumor Necrosis Factor alpha (TNF-α) and C-reactive Protein (CRP) were the most analyzed. Our meta-analysis for CRP's mean values in SSNHL groups vs. controls showed significantly higher CRP levels with a pooled overall difference of 1.07; confidence interval (CI) at 95%: 0.03; 2.11. For TNF-α, discordant results were found: three studies showed significantly higher levels in SSNHL patients vs. controls, whereas other three investigations showed lower levels in the SSNHL groups (overall pooled difference 1.97; 95% CI: -0.90; 4.84). A high between-study heterogeneity was found. Conclusions: This systematic review pointed out that, although there exists a growing literature in the field of circulatory biomarkers identification in SSNHL, there is a high heterogeneity of results and low quality of evidence. CRP resulted to be higher in SSNHL patients than in controls, while TNF-α showed more heterogeneous behavior. The data reported herein needs to be confirmed in well-designed prospective multicenter randomized studies, with the objective of improving SSNHL treatment and outcome and thereby reducing the social burden of hearing loss.

Ototoxicity of Immunosuppressant Drugs: A Systematic Review.

BACKGROUND: Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to immunosuppressant drugs has been anecdotally reported but scarcely investigated. The aim of this investigation was to systematically review the available data on ototoxicity due to immunosuppressant therapy for transplantation or autoimmune disease. METHODS: A search of electronic databases (PubMed, Web of Science, and Scopus) was performed in order to identify studies concerning otovestibular toxicity due to immunosuppressant therapy for transplantation or autoimmune disease between January 1980 and November 2020. RESULTS: Eighteen articles were considered eligible for the review. Totally 131 patients experienced ototoxicity related to immunosuppressive treatment. Hearing loss was the most common clinical manifestation (128 cases) and was mainly bilateral. Tinnitus was reported in 52 cases and vertigo in 2. The immunosuppressant drugs most frequently involved in ototoxic manifestations were calcineurin inhibitors (cyclosporine and tacrolimus), often related to their high serum levels. CONCLUSION: Immunosuppressant-related ototoxicity is clinically relevant in uncommon but definitely challenging situations. Clinicians should be aware of this and inquire about hearing impairment symptoms during therapy and refer symptomatic patients to an otolaryngologist/audiologist. Further large-scale, prospective investigations are necessary to better characterize the ototoxicity of each class of immunosuppressants.

A Critical Look Into Stapedotomy Learning Curve: Influence of Patient Characteristics and Different Criteria Defining Success.

PURPOSE: To evaluate stapedotomy learning curve with cumulative summation methodology using different success criteria (ie, air-bone gap [ABG] ≤10 dB, ABG ≤15 dB, restoration of interaural symmetry, or hearing threshold gain >20 dB), and to assess patient characteristics influencing or modifying the learning curve. METHODS: Retrospective chart review of primary and revision stapedotomy cases performed by surgeon 1 (S1, n = 78) and surgeon 2 (S2, n = 85). RESULTS: Using the classic criterion for a successful stapedotomy (ABG ≤10 dB), patients with preoperative ABG >34 dB were associated with unsuccessful procedures (S1 P = .02; S2 P = .07). Revision surgery was associated with unsuccessful outcomes (S1 P = .005; S2 P = .0012). Cumulative summation plots using different criteria did not show a linear trend of association between stapedotomy success and number of operations, but preoperative characteristics of the patients who underwent stapedotomy significantly influenced the plots. Cumulative summation plots showed an initial increasing tendency with improving results, but when ear surgeons got more skilled, they operated on more complex cases (ie, patients with higher preoperative ABG or revision stapedotomy) and they could not meet the success criteria. CONCLUSIONS: Cumulative summation plots do not seem useful to evaluate the stapedotomy learning curve, as they do not correctly deal with heterogeneous case series. The increasing complexity of the stapedotomy patients during the surgeons' career impacts on the outcome of stapedotomy and confounds the evaluation of the growing skills of the surgeon. Stapedotomy audiological success rates are strongly influenced by the success criteria used.

Idiopathic Sudden Sensorineural Hearing Loss in Children: A Systematic Review and Meta-analysis.

OBJECTIVE: Idiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon in children, and its treatment and outcome are debated. We aimed to critically review evidence in the literature about treatment options and functional outcomes of pediatric ISSNHL. Additionally, we performed a meta-analysis of the results of combined systemic-intratympanic steroid therapy versus solely systemic treatment. DATA SOURCES: A search was run in the PubMed, Scopus, and Google Scholar databases. REVIEW METHODS: Included articles were original ISSNHL case series, written in English, with a population age ranging from 2 to 19 years. Other study types (single case reports, editorials, and reviews) and case series with known etiology of sudden hearing loss were excluded. Descriptive data of patients, treatments, outcomes, and possible prognostic factors were extracted and recorded for every included study. RESULTS: Twelve articles (7 cohort and 5 case-control studies) met all the selection criteria. Based on only the studies that provided sufficient data about clinical outcome, the pooled overall recovery rate was 67.91% (95% CI, 58.34%-77.48%). No studies showed a significant difference between systemic steroid and combined systemic-intratympanic steroid. The pooled odds ratio for combined systemic-intratympanic steroid versus systemic steroid alone was 0.90 (95% CI, 0.36-2.27) based on a random effects model, ruling out any significant difference between these treatment options. CONCLUSIONS: The results of our meta-analysis did not support combination therapy more than systemic steroid alone. Further prospective clinical trials are necessary to establish evidence-based therapies.

OTOPLAN in Cochlear Implantation for Far-advanced Otosclerosis.

AIM: To evaluate OTOPLAN software in the surgical planning of far-advanced otosclerosis (FAO) candidates to cochlear implant (CI) were considered. We aimed to preliminarily investigate if this software could influence the electrode length choice, or predict surgical difficulties. METHODS: We reviewed the outcome of five consecutive FAO patients that underwent unilateral CI. OTOPLAN was used to evaluate preoperative computed tomography imaging. A comparison was made with historical data (eight FAO patients). RESULTS: The mean cochlear duct length estimated by OTOPLAN was 32.4 mm. Evaluating OTOPLAN reconstructed images, we ruled out cochlear lumen fibrosis/ossification in three FAO patients and the longest electrodes according to cochlear dimensions were preferred. We disclosed fibrosis in the middle and apical turns of two patients. These findings allowed us to change surgical plans, choosing a shorter electrode (24 and 28 mm instead of 31 mm) to avoid incomplete insertion due to cochlear fibrosis. OTOPLAN reconstructed images identified preoperatively the two patients with round window niche ossification that required additional drilling during surgery. In the present series, we experienced no incomplete insertion. In two cases out of eight historical FAO patients, array insertion (24 mm) was incomplete. One years after unilateral CI, the mean speech reception threshold and disyllabic word recognition score of the five considered FAO patients were 36 dB and 94%, respectively (39 dB and 84% for the eight historical patients). There was no facial nerve stimulation or any other complication during the 1-year follow-up. CONCLUSION: According to our preliminary results, OTOPLAN was useful for the appropriate choice of array length.

Current management of arytenoid sub-luxation and dislocation.

PURPOSE: To review the current management of arytenoid subluxation/dislocation (AS/AD) focusing on diagnostic, therapeutic, and prognostic controversies. METHODS: The international literature of the last 20 years has been considered. After the application of inclusion criteria, 20 studies were selected (471 AS/AD cases in total). RESULTS: All the included investigations were retrospective case series. AS/AD was often iatrogenic occurring at least in 0.01% of patients undergone endo-tracheal intubation. The most common symptom was persistent hoarseness. The diagnosis was made by video-laryngoscopy and neck computed tomography in most reports, while some used also laryngeal electromyography. Laryngeal electromyography was fundamental to rule out unilateral vocal fold paralysis, the main differential diagnosis. The surgical relocation of AS/AD under general or local anesthesia was achieved in about 80% of patients. CONCLUSION: AS/AD is a mechanical disorder of the larynx that can be successfully treated if promptly diagnosed. Clinical trials and multi-centric studies are necessary to set management guidelines.

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

Maspin expression and anti-apoptotic pathway regulation by bcl2 in laryngeal cancer.

OBJECTIVES: Comprehension of the interplay of pro-apoptotic and anti-apoptotic stimuli in laryngeal squamous cell carcinoma (LSCC) is crucial to understand tumor development, biological behavior and treatment response. Bcl-2 family proteins mainly regulate the apoptotic signal cascade. In some cancers, maspin seems to influence the balance between pro-apoptosis and anti-apoptosis bcl-2 family proteins. The aim of this study was to investigate the potential relationship between bcl-2 anti-apoptotic factor and the tumor suppressor maspin in LSCC. MATERIALS AND METHODS: 31 consecutive patients who underwent primary surgery and post-operative radiotherapy for LSCC were evaluated retrospectively. For each case, immunohistochemistry assays for bcl-2 and maspin were performed. Data were also collected on N-status, pT stage, grading, recurrence and disease-free survival (DFS). RESULTS: Patients with nuclear maspin pattern of expression showed a significantly lower recurrence rate (p = 0.04) and longer DFS (p = 0.0018). The expression of bcl-2 was not associated with recurrence rate or DFS either in the whole cohort or in cases with nuclear maspin pattern, while in patients with non-nuclear maspin pattern, a statistical trend was found toward a shorter DFS for bcl-2 positive cases (p = 0.062). In the multivariate model, only maspin expression pattern retained its independent prognostic significance (p = 0.006). CONCLUSIONS: Nuclear maspin pattern seemed to be an independent positive prognostic factor, while bcl-2 prognostic value was related to maspin expression pattern. Further investigations are needed to support the use of bcl-2 inhibitors in multimodality or multitarget strategies against advanced LSCCs, also considering the role and expression of tumor suppressor genes.