Role of Tumor-Infiltrating Lymphocytes and the Tumor Microenvironment in the Survival of Malignant Parotid Gland Tumors: A Two-Centre Retrospective Analysis of 107 Patients.

Background: This study aims to retrospectively investigate the prognostic significance of the tumor microenvironment, with a focus on TILs (tumor-infiltrating lymphocytes), in relation to survival in a large cohort of patients with parotid gland cancer, and it uses the method proposed by the International TILs Working Group in breast cancer. Methods: We included a cohort of consecutive patients with biopsy-proven parotid cancer who underwent surgery between January 2010 and September 2023. A retrospective review of medical records, including surgical, pathological and follow-up reports, was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group for breast cancer. Results: A weak negative correlation (p = 0.3) between TILs and time of survival and a weak positive correlation (p = 0.05) between TILs and months of survival (high TILs were correlated with longer survival in months) were identified. High TILs were weakly negatively, but not statistically significantly p (0.7), correlated with the grading of tumor; this means that high TILs were associated with low-grade tumors. Conclusions: Contrary to previous preliminary reports, this retrospective work found no statistically significant prognostic role of TILs in parotid gland malignancies. This case series represents the largest cohort ever reported in the literature and includes all malignant histological types. Future larger molecular studies may be useful in this regard.

Tissue expression of miR-449a as risk factor for occult neck metastasis in patients with cT3-T4 N0 laryngeal cancer. A pilot study.

OBJECTIVE: To explore the potential role of miR-449a as biomarker for laryngeal squamous cell carcinoma (LSCC), especially in the decision strategy of neck dissection (ND). METHODS: Each patient underwent total laryngectomy and bilateral ND (levels II-IV); during surgery, tissue samples of around 1 × 0.5 cm were extracted from both healthy tissue adjacent to the tumor and the visibly affected tumor tissue. The extraction of total RNA, encompassing miRNA, was performed using a mirVana PARIS kit. To detect miR449a, cDNA was synthesized from 200 ng of RNA using a TaqMan miRNA reverse transcription kit. RESULTS: The study group was formed of 66 patients (62 males, and 4 females) with LSCC, aged between 39 and 77 years (mean 60 + 14.56 yr). MiR-449a was up-regulated in twenty-eight tumors (42%), while it was down-regulated in 38 samples (58%). In the present study, there was a statistical relevance for miR-449a tissue expression for pN staging (p = 0.017), and PNI (p = 0.005). Eight tumors (12%) cN0 became pN + showing occult cervical lymph node metastases at the final histopathological examination, and all of these patients showed miR-449a downregulation. CONCLUSION: Super-selective ND (sparing the sub evels IIb and IV) might be the approach to cT3-T4 N0 LSCCs with upregulation of miR-449a; on the other hand, to ensure and effective control of occult neck metastases it would be appropriate to reserve elective ND (including sublevels IIb and IV) for cT3-T4 N0 LSCCs with miR-449a downregulation. Although promising, due to the small size of the cohort, the results of this work can be considered preliminary and need to be confirmed by prospective and larger studies.

Effectiveness of conservative approaches on otologic signs and symptoms in patients with temporomandibular disorders and Meniere's disease: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate the effectiveness of conservative approaches on otologic signs and symptoms in patients affected by Menière's Disease (MD) and temporomandibular disorders (TMD). METHODS: PubMed, Scopus, and Web of Science were systematically searched to identify studies presenting participants with a diagnosis of MD associated with TMD, conservative approaches as interventions, and modification of the otological signs and symptoms as outcome. RESULTS: Out of 627 articles assessed for eligibility, two studies were included. Both studies showed a significant reduction of Situational Vertigo Questionnaire after treatment, number of vertigo spells, Functional Level Scale, Dizziness Hearing Inventory, and Tinnitus Handicap Inventory, after occlusal splint therapy. No significant differences were found in terms of pure-tone audiometry average. CONCLUSION: Findings of this systematic review suggested that conservative approaches might improve vertigo in patients affected by MD and TMD. However, the low number of included studies makes difficult to draw strong conclusions.

Efficacy of rehabilitative therapies on otologic symptoms in patients with temporomandibular disorders: A systematic review of randomised controlled trials.

BACKGROUND: The term temporomandibular disorder (TMD) indicates a set of musculoskeletal conditions involving temporomandibular joint (TMJ), masticatory musculature, and related anatomical structures. Pain is the most common clinical manifestation of TMD, and the auditory system might be involved and affected, through tinnitus, dizziness, otalgia and ear fullness sensation. OBJECTIVES: The aim of this systematic review of randomised controlled trails (RCTs) was to evaluate the efficacy of rehabilitative approaches on otologic symptoms in patients with TMD. METHODS: PubMed, Scopus and Web of Science were systematically searched from the inception until 8th October 2023 to identify RCTs presenting participants with a diagnosis of TMD associated with otologic signs and symptoms, rehabilitative approaches as interventions, and modification of the otological symptoms as outcome. RESULTS: Out of 931 papers suitable for title/abstract screening, 627 articles were assessed for eligibility. Five studies were included reporting the efficacy of occlusal splint therapy, low-level laser therapies, and physical therapy in patients diagnosed whit secondary otalgia or tinnitus associated with TMD. No RCTs evaluating other otologic symptoms, ear fullness, dizziness or vertigo were found. CONCLUSIONS: Results of this systematic review suggested that rehabilitative approaches might be effective in improving secondary otalgia and tinnitus in TMD patients. Thus, further RCTs with a higher level of evidence and more representative samples should be conducted to better understand the effects of TMD therapy on otologic complains.

Instrumental Assessment and Pharmacological Treatment of Migraine-Related Vertigo in Pediatric Age.

BACKGROUND: The most frequent form of vertigo in pediatric age is represented by vertigo linked to migraine, with a prevalence of 32.7%. This group of pathologies has received a redefinition of the diagnostic criteria to adapt them to the pediatric age with a new classification of the clinical pictures. We have several kinds of problems with these conditions that often have a significant impact on patients' and parents' quality of life: the diagnostic approach involves different tools for the different age groups contained in the pediatric range; the treatment of this type of vertigo is not consolidated due to the limited availability of trials carried out on pediatric patients. Focusing on this topic, the aim of this review was to provide an update on the more recent clinical advances in the diagnosis and treatment of Vestibular Migraine (VM) in children. METHODS: We searched the PubMed, Embase, and Cochrane library databases for articles published in English from January 2015 to April 2023. The secondary search included articles from reference lists, identified by the primary search. Records were first screened by title/abstract, and then full-text articles were retrieved for eligibility evaluation. The searches combined a range of key terms ("Pediatric" AND "Childhood" AND "dizziness" OR "vertigo" AND "vestibular"). RESULTS: Migraine-related vertigo, in its most recent definitions and classifications, is the most frequent group of balance pathologies in pediatric age. The results from the various experiences present in the literature suggest a clinical approach to be integrated with the use of instrumental tests selected according to the age of the patient and the reliability of the results. CONCLUSION: Knowing the timeline of the applicability of vestibular tests and the information that can be obtained from them is fundamental for diagnostic accuracy. Therapy is strongly conditioned by the limited availability of pediatric trials and by the wide range it includes, from very young children to adolescents.

Post-operative radiotherapy in adenoid cystic carcinoma of salivary glands versus surgery alone: what is the evidence about survival and local control? A systematic review and meta-analysis.

BACKGROUND: Adenoid cystic carcinoma of the salivary glands is a relatively rare malignancy characterized by slow growth and a poor prognosis, and effective treatments remain challenging to identify. This systematic review, following the PRISMA guidelines, aimed to analyze the potential benefits of post-operative radiotherapy in terms of local control of recurrences and survival advantages when compared with surgery alone in patients with adenoid cystic carcinoma. METHODS: A comprehensive systematic review was conducted by searching the MEDLINE, Cochrane, EMBASE, and OVID databases from January 1999 to July 2022. The goal was to identify articles comparing surgery alone with surgery plus postoperative radiotherapy for adenoid cystic carcinoma of the salivary glands. Downs and Black Checklist was used to assess the methodological quality and risk of bias of each included study. The data analysis was performed using Review Manager version 5.4.1. RESULTS: This review included 8 studies comprising a total of 3103 patients, divided based on the analyzed outcomes. The pooled odds ratio for overall survival at 5 years was 0.87 (95% confidence interval 0.43-1.76, p = 0.70), and at 10 years was 1.23 (95% confidence interval 0.69-2.16, p = 0.48). In both cases, no statistically significant differences were observed. However, the pooled odds ratio for local control at 5 years was 3.37 (95% confidence interval 1.35-8.42, p = 0.009), providing strong support for the use of post-operative radiation. CONCLUSIONS: The findings from the meta-analysis suggest that post-operative radiotherapy significantly improves local control in patients with adenoid cystic carcinoma. However, there was no statistically significant increase in survival at 5 and 10 years. It is essential to note that the quality of the studies included in this meta-analysis ranged from fair to poor. To better clarify the indications for post-operative radiotherapy, future high-quality research is needed, particularly with improved stratification of patient groups. Additionally, it is important to recognize that achieving local control in adenoid cystic carcinoma is crucial for enhancing the overall quality of life for patients. We acknowledge that this review was not registered in the PROSPERO database, and the data pooling was conducted using a random effects model.

Enhancing the therapeutic potential of intravenous glycerol for Meniere's disease: Robust results from an extensive patient cohort.

INTRODUCTION: Meniere's disease (MD) is an idiopatic condition characterized by recurrent attacks of vertigo, hearing loss, tinnitus, and aural fullness, affecting quality of life. Intravenous glycerol has shown potential as a therapeutic option. This study evaluates its efficacy in a larger patient cohort. MATERIALS AND METHODS: Retrospective study with 168 patients having unilateral MD unresponsive to dietary restrictions. Intravenous 10 % glycerol with 0.9 % sodium chloride was administered for six months. Audio-vestibular assessments and questionnaires were used. RESULTS: Significant improvements in vertigo control observed. 7.1 % achieved complete control, and 58.3 % had substantial control. Quality of life measures improved, and audiometry thresholds remained unchanged. No major adverse events reported. DISCUSSION: Intravenous glycerol effectively controlled vertigo and improved MD patients' quality of life. Limitations include lack of a control group and a relatively short-term follow-up. Future prospects include randomized controlled trials and optimization of treatment protocols. CONCLUSION: Intravenous glycerol shows promise as a therapeutic option for MD, with notable improvements in vertigo control and quality of life. Further research is needed for validation and optimization.

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study.

PURPOSE: Meniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. MATERIALS AND METHODS: This study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. RESULTS: Before treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. CONCLUSIONS: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

Correlation Between Air-Bone Gap and Vestibular Aqueduct Size in Enlarged Vestibular Aqueduct Syndrome: A Systematic Review.

The purpose of this review was to evaluate the air-bone gap with vestibular aqueduct size in enlarged vestibular aqueduct syndrome. According to the PRISMA guidelines we conducted a systematic review of the literature. Published international articles in English from 2000 to 2022 were screened, checking for studies that evaluated the air-bone gap of patients affected by enlarged vestibular aqueduct syndrome and the size of vestibular aqueduct. Data related to the hearing assessment and imaging investigation of enrolled participants were extracted. The chosen primary outcome measure was the correlation between air-bone-gap and vestibular aqueduct size. The database search allowed us to screen 485 articles and to select 5 articles discussing this topic for a total of 349 patients. Two studies showed a positive correlation between air-bone gap and vestibular aqueduct size, one only a trend and two no correlation. To date, it is not possible to draw conclusions whether or not there is a positive correlation between air-bone gap and vestibular aqueduct size in enlarged vestibular aqueduct syndrome. Higher quality studies would be conducted with standardized outcome measures to clarify the specific research question.

Surgical Management of Endolymphatic Sac Tumor: A Systematic Review and Meta-Analysis.

The aim of our study was to report rates of facial nerve palsy and residual tumor following surgical intervention and subsequent tumor recurrence in patients with endolymphatic sac tumors. A systematic literature review of preoperative assessment and surgical management is also included. Studies including patient/s affected by sporadic or von Hippel-Lindau disease related endolymphatic sac tumors, reporting levels of facial nerve function, residual and recurrence pathology following a surgical procedure, were considered. Data were combined for proportional meta-analysis, and the selected studies' methodological quality was also evaluated. Overall 34 papers, including 202 subjects (209 cases of endolymphatic sac tumors) were analyzed. Pooled proportion rate (95% CI) of overall facial nerve palsy was 39.7% (28.2-51.9) and residual tumor was 16.5% (10.3-23.7) after surgical procedure. Pooled proportion rate (95% CI) of tumor recurrence was 14.0% (9.7-19.3) during a mean follow-up period of 49.7 months (8-136). Our results showed that preoperative facial nerve function is impaired in almost 30% of patients with endolymphatic sac tumors. Surgical management of endolymphatic sac tumor may cause a worsening of facial nerve function in a low percentage of treated subjects. Residual and/or recurrence of endolymphatic sac tumors are not rare events, and follow-up strategies should be designed accordingly.

Vestibular Impairment in Patients with Vestibular Schwannoma: A Journey through the Pitfalls of Current Literature.

Vestibular Schwannoma is the most common tumour of Ponto Cerebellar Angle and is capable of strongly impacting the patient's quality of life. In recent decades, the proposals for the management of the disease have multiplied, just as the diagnostic capacity has improved. While in the past, the primary objective was the preservation of the facial function, and subsequently also of the auditory function, the attention to the vestibular symptomatology, which appears to be one of the main indicators of deterioration of quality of life, is still unsatisfactory. Many authors have tried to provide guidance on the best possible management strategy, but a universally recognized guideline is still lacking. This article offers an overview of the disease and the proposals which have advanced in the last twenty years, evaluating their qualities and defects in a critical reading.

Diabetes Mellitus and Hearing Loss: A Complex Relationship.

Background and Objectives: Discussion is open about the relationship between diabetes (DM) and hearing loss (HL). There is a lot of evidence in the literature suggesting a causal link between these conditions, beyond being considered simple comorbidities. The difficulty in identifying populations free from confounding factors makes it difficult to reach definitive conclusions on the pathophysiological mechanisms at play. Nonetheless, there is numerous evidence that demonstrates how the population affected by DM is more affected by sensorineural HL (SNHL) and exhibit a higher prevalence of idiopathic sudden sensorineural HL (ISSNHL). Materials and Methods: Articles reporting potentially relevant information were reviewed, and the most significant results are discussed in this article. Starting from the possible mechanisms relating to auditory impairment in the diabetic condition, this article summarizes the studies on auditory evaluation in subjects with DM1 and DM2 and addresses the relationship between DM and ISSNHL. Results: DM is considered a risk factor for SNHL, although some studies have reported no relationship when the associations were adjusted for age, gender, and hypertension. Macro and microvascular insults that cause decreased blood flow, oxygen exchange, and ion transport are major complications of hypertension and DM and can have a direct effect on the sensory and support cells of the cochlea. Conclusions: Given the difficulty of carrying out studies on populations without confounding factors, new laboratory studies are strongly required to clarify which specific physiopathological mechanisms underlie the diabetic damage caused to the hearing organs and how pharmacological management may contribute to counteracting the pathophysiological effects of the diabetic condition on the auditory system.

The Role of Quantic Molecular Resonance (QMR) in the Treatment of Inferior Turbinate Hypertrophy (ITH): Our Experience With Long-Term Follow-Up in Allergic and Nonallergic Rhinitis Refractory to Medical Therapy. Preliminary Results.

OBJECTIVE: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. METHODS: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. RESULTS: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. CONCLUSIONS: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes.

Cerebrospinal Fluid Leak During Stapes Surgery: The Importance of Temporal Bone CT Reconstructions in Oblique Anatomically Oriented Planes.

Stapes gusher is a massive flow of perilymph and cerebrospinal fluid leak that fills the middle ear immediately after surgical opening of the labyrinth, such as during stapedectomy. Stapes gusher usually occurs as the result of a congenital malformation that causes an abnormal communication between the perilymphatic space and the subarachnoid space involving the internal auditory canal or the cochlear duct. To date, the potential risk of stapes gusher cannot be assessed preoperatively, as there are not pathognomonic signs suggestive of this complication. However, high-resolution computed tomography scan (HRCT) of the temporal bone can provide information that may help recognizing patients at risk. Recently, an anatomic evaluation of the inner ear with oblique reformation at HRCT has been described. This reformation offers a new and more detailed topographic vision of temporal bone structures compared to the classic axial and coronal planes and may help identifying anatomical alterations otherwise not visible. In this article, we present a case of stapes gusher and the role of preoperative HRCT with oblique reformation in its prevention.

Specific local nasal immunotherapy: Single center experience on 324 patients.

OBJECTIVE: To evaluate the efficacy and safety of specific local nasal immunotherapy (LNIT) in patients with allergic rhinitis. MATERIALS AND METHODS: A retrospective single-center study of 324 patients with allergic rhinitis (191 allergic to mites, 133 allergic to Grarninaceae or Parietaria pollen) treated with specific LNIT was carried out. As control group, 158 patients without allergic rhinitis were enrolled. All patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test and the rhinomanometric analysis confirm the result with a difference statistically significant. No differnces in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is a valide alternative to subcutaneous and sublingual administration. It is effective, safe, well tolerated by the patient, it can be done at home with fewer systemic reactions.

Combination of Hyperbaric Oxygen Therapy and Oral Steroids for the Treatment of Sudden Sensorineural Hearing Loss: Early or Late?

Background and Objectives: Several treatments are available for sudden sensorineural hearing loss (SSNHL), but no studies have compared the different treatments based on the delay from the onset of the disease. Our study aims to compare the effect of hyperbaric oxygen therapy (HBOT), oral steroids (OS) and combination of both therapies (HBOT + OS) for treating SSNHL. Materials and Methods: This randomized study analyzed 171 patients with SSNHL. Patients were evaluated by pure tone audiometry test (PTA) at baseline (T0) and 20 days after treatment (T1). Three groups were available HBOT-A-, OS-B- and HBOT + OS-C-. After baseline PTA, patients were randomly assigned to each group. Statistical analysis was performed by one-way ANOVA and Chi-square. Results: Patients in the HBOT + OS and HBOT groups improved their auditory function (p < 0.05). HBOT was the best choice for treatment when started by 7 days from SSNHL onset, while HBOT + OS in case of late treatment. Profound SNHL recovered equally by HBOT and HBOT + OS (p < 0.05). Upsloping SNHL obtained better auditory results by HBOT compared to HBOT + OS (p < 0.05). Downsloping and flat SSNHL had the most improvement with HBOT + OS compared to HBOT only (p < 0.05). Conclusions: Combination of HBOT and OS is a valid treatment for SSNHL both in case of early and late treatment. Combination of HBOT and OS was the choice with the best results in case of treatment started >14 days from symptom onset.

The pharmacological treatment of acute vestibular syndrome.

Acute vestibular syndrome (AVS) represents a clinical picture that involves urgent management due to the important procession of symptoms accompanying the event, which can be positively or negatively influenced by therapeutic choices and intervention timing. This forces a differential diagnosis and therapeutic choices to be made in conditions that are not always favorable and often not in the specialist field. In this work, we will examine in detail the pharmacological therapeutic possibilities, correlating them to the differential and, as far as possible, to the etiological diagnosis. In particular, the pharmacological possibilities for the two main conditions we can face will be investigated, namely, vestibular neuritis and posterior circulation stroke.

Comparison between overlay and underlay primary myringoplasty: retrospective analysis on anatomical and functional results in 497 adult patients

PURPOSE: Retro-auricular approach using an autologous graft is the main surgical method for myringoplasty (MPL). Endaural and transcanal or endoscopic approaches are also used. There is no definitive consensus on the best MPL surgical technique. The aim of this study is to compare the two most used technique, over and underlay MPL, to evaluate the difference in anatomical and functional outcomes. MATERIALS AND METHODS: We made a retrospective analysis of 497 adult patients who underwent underlay or overlay primary MPL, between 2010 and 2018, and evaluated the difference in anatomical and functional outcomes. RESULTS: Successful functional results, evaluated 18 months after surgery, were obtained in 380 patients (76,4%); the underlay MPL obtained a successful result in 85% of patients, while the overlay technique in the 68%. We observed anatomical failure in 13.4% patients, in detail 9,8% of underlay MPL and 17,2% of overlay MPL had an anatomical failure. CONCLUSION: Our results show less complications related to the underlay technique. We believe that this remains the technique to prefer, except in subtotal or wide anterior perforations that could be better managed using the overlay technique.