Fitostimoline® in fibro-endoscopic and trans-nasal trans-speculum septoplasty as a beneficial tool to improve post-surgical outcome: Preliminary results of a case-control study.

OBJECTIVES: Topic treatment can be useful to improve short and long-term nasal outcomes after nasal surgery, reducing discomfort and risk of synechia. This study aimed at evaluating the effect on clinical outcomes of nasal packaging using Fitostimoline® gauze in FESS and septoplasty. METHODS: A case-control study on hospitalized patients was performed in a tertiary referral center. The control group included 20 patients treated with the standard surgical protocol for septoplasty and standard nasal packaging; treatment group included 21 patients underwent same surgical procedure but in whom the nasal tampon was wrapped with a gauze containing Fitostimoline® before being placed into the nose. RESULTS: Patients in treatment group had better outcomes than control; nasal mucosa showed better healing - recovery of normal color- in those patients in whom we applied the Fitostimoline® gauze around tampons. Moreover, 100 % patients in the treatment group did not refer discomfort during at tampon removal versus 60 % subjects in the control group who referred pain, tension or tearing during the same action. CONCLUSION: Our results, although preliminary because of the small cohort of subjects included, suggest that the apposition of a gauze with Fitostimoline® after nasal surgery might improve the mucosal healing with consequent reduction of patients discomfort during the post-surgical period.

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.

Parapharyngeal space tumors: a twenty-year single-center retrospective analysis on the effectiveness of transcervical and transoral approaches on local control and disease-specific survival.

INTRODUCTION: To retrospectively analyzed our twenty-years single-center experience in the treatment of PPS tumors, focusing on the selection of surgical approach and the survival outcome. METHODS: Tumors involving the PPS between January 2000 and February 2022 were retrospectively included. The surgical approach was dictated by the localization of the tumor, its dimensions, the relation to anatomic structures and its etiology. RESULTS: 34 patients were included in the study. The median age was 50.5 yr, with a gender female prevalence. Most tumors were benign and non recurrent. 20 tumors were treated through lateral approach (transcervical or transcervical-transparotid), 11 through medial approach (transoral), and only 3 tumors were approached by multiple corridors. The 5 years disease free survival (DFS) was 78.8 % (CI 78-79.3 %). CONCLUSIONS: In our experience, the transcervical and transoral approaches can be considered the ideal surgical approach to manage tumors of PPS, especially in cases of benign neoplasms.

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.

PURPOSE: Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. METHODS: This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA-LUT alone; (3) twice daily um-PEA-LUT alone; or (4) combination of once daily um-PEA-LUT with olfactory training. Olfactory testing (Sniffin' Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T0, T1, T2 and T3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. RESULTS: All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA-LUT alone, and 41.6% receiving once daily um-PEA-LUT alone (p < 0.00001). Patients receiving treatment with um-PEA-LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo (p < 0.0001.) CONCLUSIONS: Olfactory training plus once daily um-PEA-LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. TRIAL REGISTRATION: 20112020PGFN on clinicaltrials.gov. LEVEL OF EVIDENCE: 1b (Individual Randomized Clinical Trial).

Comment on Marra et al. Metastatic Renal Cell Carcinoma to the Soft Tissue 27 Years after Radical Nephrectomy: A Case Report. Medicina 2023, 59, 150.

Recently, Marra et al. [...].

Reconstruction of hypopharyngeal defects with anterolateral thigh free flap: A single-center retrospective analysis.

INTRODUCTION: Reconstruction of expanded hypopharyngeal defects following laryngo-hypopharyngectomy for surgical treatment of primary is still a challenge for head and neck surgeons. Tradiotionally, jejunal or radial forearm flaps are the common reconstructive choice. Recently, the anterolateral thigh (ALT) free flap has served for pharyngoesophageal reconstruction. The goal of this work is to describe a retrospective analysis about a five-year single-center experience in the reconstruction of post-operative hypopharyngeal defects with ALT free flap. METHODS: A single-center retrospective study was performed, including patients treated for patients who underwent tumor surgery involving hypopharynx with ALT free flap reconstruction from 2015 to 2020. Exclusion criteria were paediatric (0-18 years) patients, and the absence of follow-up. RESULTS: The study included 23 adult patients. The mean size of the flap was 90 cm2 (range 60-130 cm2). The mean time required to harvest the antero-lateral tight flap was 70 min (range 35-120 min). The median age was 46.3 years (SD 15.81, range: 19-84 years), with a gender female prevalence (F = 48, M = 33). Mean follow-up was 77.7 months (min 4-max 361, SD 72.46). One patient (4.4 %) showed a hypopharyngeal stenosis. CONCLUSION: ALT free flap represents a successful and versatile reconstructive option for hypopharyngeal defects extended to oropharynx and/or larynx following total laryngectomy with circumferential or partial hypopharyngectomy, regardless of the functional and aesthetic results, with minimal donor-site complication.

Diagnosis and treatment delay of head and neck cancers during COVID-19 era in a tertiary care academic hospital: what should we expect?

BACKGROUND: Since the spreading of SARS-CoV-2 from China, all deferrable medical activities have been suspended, to redirect resources for the management of COVID patients. The goal of this retrospective study was to investigate the impact of COVID-19 on head and neck cancers' diagnosis in our Academic Hospital. METHODS: A retrospective analysis of patients treated for head and neck cancers between March 12 and November 1, 2020 was carried out, and we compared these data with the diagnoses of the same periods of the 5 previous years. RESULTS: 47 patients were included in this study. We observed a significative reduction in comparison with the same period of the previous 5 years. CONCLUSIONS: Our findings suggest that the COVID-19 pandemic is associated with a decrease in the number of new H&N cancers diagnoses, and a substantial diagnostic delay can be attributable to COVID-19 control measures.

Cribriform adenocarcinoma of the tongue and minor salivary glands: a systematic review of an uncommon clinicopathological entity.

INTRODUCTION: Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a rare neoplasm, accounting for less than 1% of salivary gland tumors. In the past it has been considered a possible variant of polymorphous low-grade adenocarcinoma (PLGA), while nowadays it is accepted as a provisional entity in the WHO classification. The aim of this paper is to systematically review the existing literature about CATMSG with a particular attention to differential diagnosis and prognostic factors. METHODS: This study was performed in accordance with the PRISMA checklist. A comprehensive search in PubMed, Cochrane, and Google Scholar databases was carried out in June 2021, in partnership with a medical librarian, without time restriction. Search items include the following keywords: "cribriform adenocarcinoma of the tongue" OR "cribriform adenocarcinoma of the tongue and minor salivary glands." RESULTS: A total of 56 patients were evaluated. Patient age across the studies ranged from 13 to 85 years (mean 59.6 year). The most common site of involvement was the tongue (58.9%), followed by palate (19.6%), tonsil (7.1%), buccal (3.6%) and reticular mucosa (3.6%), lip (3.6%), retromolar pad (1.7%), and floor of the mouth (1.7%). Lymph node involvement at the diagnosis was very common (58.9%), while there was no evidence of patients diagnosed with metastatic disease. The most common surgical approach was surgical excision (17, 30.3%); neck dissection was performed in 16 patients (28%). Radiotherapy was the most common adjuvant treatment reported (46.4%); only one patient underwent adjuvant chemotherapy (1.7%). Five patients experienced a recurrence (8.8%). CONCLUSION: To our knowledge, only 56 five cases of CATMSG have been previously described. The results of this review seem to confirm the low frequency of relapses and distant metastases, but we observed that almost 60% of cases presented with cervical lymph node involvement. In our opinion, CATMSG should be considered as a distinct tumor entity from PLGA.

Acinic cell carcinoma of the parotid gland: Timeo Danaos et dona ferentes? A multicenter retrospective analysis focusing on survival outcome.

OBJECTIVES: To analyze the demographic data, surgical and adjuvant treatment data and the survival outcomes in adult patients affected by acinic cell carcinoma of the parotid gland (AciCC). METHODS: A retrospective multicenter analysis of patients treated for AciCC of the parotid gland from 2000 to 2021 was performed. Exclusion criteria were pediatric (0-18 years) patients, the absence of follow-up and patients with secondary metastatic disease to the parotid gland. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: The study included 81 adult patients with AciCC of the parotid gland. The median age was 46.3 years (SD 15.81, range 19-84 years), with a gender female prevalence (F = 48, M = 33). The mean follow-up was 77.7 months (min 4-max 361, SD 72.46). The 5 years overall survival (OS) was 97.5%. The 5 years disease-free survival (DFS) was 60%. No statistical differences have been found in prognosis for age (< 65 or ≥ 65 years), sex, surgery type (superficial vs profound parotid surgery), radicality (R0 vs R1 + Rclose), neck dissection, early pathologic T and N stages and adjuvant therapy (p > 0.05). CONCLUSION: This study did not find prognostic factor for poorest outcome. In contrast with the existing literature, our results showed how also high-grade tumours cannot be considered predictive of recurrence or aggressive behaviour.

Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation.

OBJECTIVE: ERCC1 (excision repair cross-complementation group 1) expression predicts survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation. In order to evaluate the predictive role in the adjuvant setting, we investigated ERCC1 expression in radically resected HNSCC patients who underwent surgery and cisplatin chemoradiation. METHODS: ERCC1 expression levels were determined by immunohistochemistry in primary tumor tissues from 48 patients with stage III-IV cancers. The median follow-up was 38.5 months (range: 5-121). RESULTS: High ERCC1 expression was observed in 36 (75%) patients. Univariate analysis showed that patients with high levels of ERCC1 had significantly worse disease-free survival and overall survival (OS) than patients with low levels (HR = 7.15; 95% CI, 1.68-30.35; p = 0.008 and HR = 9.90; 95% CI, 1.33-73.96; p = 0.025, respectively). In the multivariate analysis, high ERCC1 expression (HR = 7.36; 95% CI, 1.72-31.4; p = 0.007) together with high-risk category (HR = 2.69; 95% CI, 1.01-7.18; p = 0.048) were the best predictors for relapse. High ERCC1 expression was the only unfavorable independent determinant for OS (HR = 9.53; 95% CI, 1.27-71.35; p = 0.028). CONCLUSIONS: This investigation suggests that ERCC1 expression might be useful to predict prognosis in radically resected HNSCC patients treated with surgery and chemoradiation.

Well and intermediate differentiated laryngeal chondrosarcoma: toward conservative surgery?

Chondrosarcoma of the larynx is a relatively rare malignant tumor. In the world literature, only 600 cases of laryngeal chondrosarcoma (LCS) have been reported. It is the most frequent non-epithelial tumor of the larynx (0.07-2% of all cancers), usually occurring on the cricoid. We present six cases of well-intermediate differentiated grade chondrosarcoma of the larynx, diagnosed between the fifth and seventh decades of life, in the absence of relevant risk factors. All cases were subjected to a conservative surgical approach, either endoscopic using remodeling transoral laser surgery, or open neck via a supratracheal partial laryngectomy (STL), sparing laryngeal function. All patients are free from recurrence with a minimum follow-up of 31 months. All were ultimately decannulated, are able to tolerate a quite normal diet and to speak satisfactorily. Conservative laryngeal surgery is effective because chondrosarcoma is often a low-grade tumor showing slow growth. The criteria for choosing the type of surgery was based on the age of the patient (elderly patient > favoring an endoscopic approach), on the rate of involvement of the cricoid and on the involvement of the cricoarytenoid joints (if possible to save a cricoarytenoid unit > favoring a STL). By extending the inferior limit of the resection to include a large part of the cricoid cartilage, supratracheal partial laryngectomies expanded the indications to some LCSs not involving the entire cricoid lamina sparing laryngeal function and avoiding the need for total laryngectomy.

Impact of Surgeon's Experience and Tumor's Nature in the Use of Intraoperative Facial Nerve Monitoring in Superficial Parotidectomy. Preliminary Results from a Single-Center Retrospective Analysis.

To assess the effectiveness of intraoperative facial nerve monitoring (IFNM) compared to non-monitoring in the prevention of post-operative facial nerve palsy during superficial parotidectomy. Patients treated with curative intent for parotid gland tumors between January 2020 and January 2022 were included. The study population has been divided in 2 groups, based on IFNM: the group A included patients operated with IFNM, whilst group B was the non-monitoring group. A further classification focused on the pathologies and the surgeons' experience. The study group included 58 patients, 27 female and 31 male. The mean age was 45.7 yr (range 36-78). No statistical difference has been found in post-operative HB grade between group A and B. The analysis of patients affected by pleomorphic surface lobe adenomas of the parotid did not show a statistical difference in HB outcome (p > 0.05). The analysis of the effect of surgeons' experience in IFNM advantage did not show statistical difference for superficial parotid tumors. The results of the present study suggest that the use of IFNM during parotid surgery is not mandatory to preserve the VII nerve function, both in case of primary tumor and in case of recurrence, and even when surgery is performed by less experienced surgeon compared to those cases treated by a more experienced surgeon.

A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx.

BACKGROUND: The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. METHODS: All consecutive patients with biopsy-proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. 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. RESULTS: The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. CONCLUSIONS: Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.

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.

A pilot study to evaluate the expression of microRNA­let­7a in patients with intestinal­type sinonasal adenocarcinoma.

Despite its histological resemblance to colorectal adenocarcinoma, there is little information about the molecular events involved in the pathogenesis of intestinal-type sinonasal adenocarcinoma (ITAC). The present study investigated the possible role and clinical value of microRNA (miR)-let-7a, a head and neck squamous cell carcinoma-related miR, in a well-characterized and homogeneous cohort of patients with ethmoidal ITAC associated with occupational exposure, treated by primary surgery. miR-let-7a expression levels were analyzed in 23 pairs of ethmoidal ITAC and adjacent normal formalin-fixed paraffin-embedded tissues by reverse transcription-quantitative PCR. The expression was evaluated in tumor and healthy tissues according to: Tumor grade (G) of differentiation and extension, and pTNM stage, and presence/absence of recurrence. Comparisons within and between groups were performed using two-tailed Student's paired t-test and one-way ANOVA with Tukey's post hoc test. P<0.05 was considered to indicate a statistically significant difference. miR-let-7a expression in ethmoidal ITAC tissues was significantly lower than that in adjacent normal tissues (P<0.05; mean expression level ± SD, 1.452707±1.4367189 vs. 4.094017±2.7465375). miR expression varied with pT stage. miR-let-7a was downregulated (P<0.05) in advanced stages (pT3-pT4) compared with earlier stages (pT1-pT2). Furthermore, downregulation of miR-let-7a in ITAC was associated with poorly-differentiated (G3) cancer (P<0.05). No other associations were observed between miR-let-7a expression and the other clinicopathological parameters, including disease-free survival. In conclusion, downregulation of miR-let-7a in ITAC was associated with advanced-stage (pT3 and pT4) and poorly-differentiated (G3) disease, suggesting that the mutation of this gene, combined with additional genetic events, could serve a role in ITAC pathogenesis.

Recurrent acinic cell carcinoma of the parotid gland with lateral skull base invasion: Case report and discussion of the literature.

Medical records of a 76-year-old woman with a recurrent acinic cell carcinoma of the left parotid gland with lateral skull base invasion were reviewed. She underwent subtotal petrosectomy followed by radiation therapy. After surgery, she remained disease-free for more than 16 months.

Vitamin D Deficit as Inducer of Adenotonsillar Hypertrophy in Children with Obstructive Sleep Apnea-A Prospective Case-Control Study.

(1) Objective: This prospective case-control study aimed to assess the level of serum vitamin D comparing pediatric non-allergic patients with obstructive sleep apnea (OSA) and healthy controls. (2) Methods: The period of the enrollment was from November 2021 to February 2022. Children with uncomplicated OSA caused by adenotonsillar hypertrophy (ATH) were recruited. Allergy was excluded by skin prick test (SPT), and the determination of serum IgE level using ELISA test. Plasma concentration of 25-hydroxy vitamin D (25-OHD) was quantitatively determined; then, the vitamin D concentration in patients was compared with healthy controls matched for sex, age, ethnicity, and characteristics. (3) Results: Plasma 25-OHD levels were significantly lower in patients than in healthy subjects (mean 17 ng/mL, 6.27 DS, range 6-30.7 ng/mL, vs. mean 22 ng/mL, 9.45 DS, range 7-41.2 ng/ ml; p < 0.0005). The prevalence of children with vitamin D deficiency was significantly higher in the ATH group than controls. The plasma 25-OHD level did not change following the ATH clinical presentation (III or IV grade according to the Brodsky scale), while the different categories of 25-OHD status (insufficiency, deficiency, and adequacy) in the ATH group were statistically significantly different (p < 0.001) from healthy controls. (4) Conclusions: This study identified statistically significant differences between the ATH group and control regarding the plasma concentration of vitamin D; this data, despite not being directly linkable to the lymphoid tissue hypertrophy (p-value not significant), might suggest a negative effect of vitamin D deficit on the immune system.

Systematic Review of Management and Survival Outcome of Parotid Cancers with Lateral Skull Base Invasion.

Lateral skull base involvement from parotid cancers is a rare condition and is considered a poor prognostic indicator. The aim of this study was to systematically review the literature of parotid tumors with temporal bone invasion to analyze the survival outcome. A systematic literature review was performed in August 2022, without time limits, and 289 patients affected by parotid gland cancers and lateral skull base involvement were included. The most common symptoms in parotid tumors at the onset were indolent mass, facial weakness, pain, and hearing loss; the chi-square value is 23.1063, with a statistically significance (p = < 0.000121). The five most common histologies were adenoid cystic carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, and squamous cell carcinoma. The facial nerve function after surgery showed statistically significance (functional vs. non-functional; chi-square was 91.7698, p = < 0.00001). Mean follow-up was 36.2 months (range 0.3-192). At the last follow-up, more patients died of disease (DOD; 60/289, 21%) than other causes (DOOC; 5/289, 2%). There is a statistically significant correlation between patients died for tumor (DOD) and patients died for other causes (DOOC) (p = < 0.0001), suggesting that the lateral skull base invasion negatively impacts on survival. Basing on the results of our systematic review, lateral skull base involvement from parotid recurrent/advance tumors should be considered a poor prognostic factor, as the majority of patients die due to this condition. It also would be necessary to have "clear"works, with full data (demographic, clinical, surgical data), and with a longer follow up, in order to assess the best treatment modality of these patients.