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.

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.

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.

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.

A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland.

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist. RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

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.

Bilateral and Ipsilateral Central Neck Dissection in Total Thyroidectomy: a Long Term Comparison of Complications.

The role of prophylactic central compartment neck dissection (CCND) in total thyroidectomy (TT) is controversial in patients without clinically evident lymph nodes metastasis (cN0) because of association with transient and permanent hypoparathyroidism (HPT) as well as transient and permanent recurrent laryngeal nerve (RLN) injury. Instead of bilateral central neck dissection (bCCND), ipsilateral central compartment neck dissection (iCCND) has recently been proposed as a safer, alternative treatment for selected patients. The aim of this study is to characterize the morbidity that CCND (ipsilateral and bilateral) adds to TT. We enrolled 453 patients: Group A (316 patients) underwent TT alone, Group B (86 patients) underwent TT + iCCND, Group C (51 patients) underwent TT + bCCND. We compared the rates of RLN injury and HPT in three groups and data analysis showed that iCCND was associated with increased rate of transient HPT but not permanent HPT and bCCND was associated with increased rate of transient and permanent HPT, when compared with TT alone. Further studies are needed to evaluate the clear advantages of CCND (both ipsilateral and bilateral), but this should be considered in the context of an higher risk of surgical complications (especially transient and permanent hypoparathyroidism), in comparison with TT alone.

Prevention of withdrawal symptoms in alcoholic patients with head and neck cancer.

BACKGROUND: The role of alcohol abuse is common in the onset of cancer of the upper aerodigestive tract, especially that affecting the tongue, floor of the mouth, palatine tonsil and piriform sinus. The consequences of the abuse of alcohol immediately after surgery in these patients are less known. But they are very important to achieve good final results. METHODS: To try to understand the best treatment for withdrawal symptoms in a group of Italian patient with head and neck cancers, we administered a 10-item questionnaire. Subsequently, we decided to send the questionnaire to the main Italian centers of head and neck oncology using the platform of online surveys SurveyMonkey. RESULTS: The results show clearly that it is not easy, within the Italian "latin" culture and lifestyle to correctly identify the alcoholic patient (patients in the last stage of the of the disease with a "behavioral dependency") and that the centers which address these problems mostly use a drug treatment, employing in particular two classes of drugs, associated or not with thiamine, with a varying quantity of other vitamins. CONCLUSIONS: It is important to know the early withdrawal syndrome to assess the ideal treatment. We propose a personal protocol to present this complication.

First Extraction of Transversity from a Global Analysis of Electron-Proton and Proton-Proton Data.

We present the first extraction of the transversity distribution in the framework of collinear factorization based on the global analysis of pion-pair production in deep-inelastic scattering and in proton-proton collisions with a transversely polarized proton. The extraction relies on the knowledge of dihadron fragmentation functions, which are taken from the analysis of electron-positron annihilation data. For the first time, the transversity is extracted from a global analysis similar to what is usually done for the spin-averaged and helicity distributions. The knowledge of transversity is important for, among other things, detecting possible signals of new physics in high-precision low-energy experiments.

Steroid-Eluting Ethmoidal Stent Versus Antero-Posterior Ethmoidectomy: Comparison Of Efficacy And Safety In Allergic Patients.

BACKGROUND: Allergic and chronic rhinosinusitis is a disabling pathological condition with an 8% prevalence in the European population and 5% in the Italian one. The ethmoidal sinus is the first one involved in the inflammation. The typical surgical procedure to manage ethmoidal sinusitis is an endoscopic antero-posterior ethmoidectomy. Recently introduced on the European market balloon called Relieva Stratus MicroFlow Spacer can be inserted within the ethmoid, with a local slow release of a steroid drug. This study had the aim to evaluate the efficacy and safety of the steroid-eluting ethmoidal stent in the management of allergic chronic rhinosinusitis in comparison with the traditional endoscopic ethmoidectomy. Methodos: 70 allergic patients who presented chronic rhinosinusitis were randomly divided into 2 groups and receive respectively the steroid-eluting ethmoidal stent or endoscopic ethmoidectomy. RESULTS: The most significant observation coming from the comparative analysis of the results is the substantial equivalence of the treatment with the steroid-eluting ethmoidal stent (SEES) compared with endoscopic ethmoidectomy in the management of ethmoid chronic rhinosinusitis with the exception of a reduction of overall discomfort and nasal secretion and better functional results at rhinomanometry in the steroid-eluting ethmoidal stent group. CONCLUSION: in our experience, the SEES was efficacious in the treatment of allergic patients with ethmoidal CRS when conventional medical treatment had failed, or when wishing to avoid the classic endoscopic ethmoidectomy (EE). However, further long-term studies will be performed in order to confirm the safety and stability, over time, of the results obtained.

TNM classification of the oral cavity carcinomas: some suggested modifications.

TNM system is a universally recognized cancer classification. It's based on the assessment of anatomical extent of tumor (T), nodal (N) and distant metastases (M). The first edition of TNM was published in 1968 and has since been updated several times. Relevant characteristics that affect prognosis prognosis, such as depth of invasion, tumor volume, surgical margin infiltration, and the number of involved nodes as well as the presence of extracapsular spread (such data should be determined by the pathologist and included in pTNM staging ­ ed. note) are not included in the TNM classification. Following a discussion on most recent classification updates we will discuss the factors, which in our opinion and in concordance with the most recent literature, deserve special consideration and influence management of oral carcinomas.

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.

Expression of E-cadherin and α-catenin in T1 N0 laryngeal cancer.

AIM: To determine whether modulation of expression of cell adhesion molecules occurs in neoplastic transformation of laryngeal epithelium and to investigate their possible role in clinical outcome. MATERIALS AND METHODS: Fifty-five T1 N0 laryngeal biopsies were tested by immunohistochemistry for the E-cadherin/α-catenin adhesion complex. RESULTS: High immunohistochemical expression of E-cadherin and α-catenin was found in 18% and 53% cases, respectively. Expression of both adhesion molecules decreased according to histological grading; a significant relationship was particularly found between high E-cadherin expression and G1 cases (p=0.013). High E-cad-herin expression was statistically associated with in situ carcinoma (p=0.006). Non-statistical significance was evidenced between these adhesion molecules and tobacco use or site of occurence. Regarding clinical outcome, recurrence was associated with low expression of both adhesion molecules. CONCLUSION: E-cadherin and α-catenin down-regulation might be associated with neoplastic transformation in laryngeal tissues and might be regarded as a risk factor for clinical recurrence.

Constraining quark angular momentum through semi-inclusive measurements.

The determination of quark angular momentum requires the knowledge of the generalized parton distribution E in the forward limit. We assume a connection between this function and the Sivers transverse-momentum distribution, based on model calculations and theoretical considerations. Using this assumption, we show that it is possible to fit nucleon magnetic moments and semi-inclusive single-spin asymmetries at the same time. This imposes additional constraints on the Sivers function and opens a plausible way to quantifying quark angular momentum.

First glances at the transversity parton distribution through dihadron fragmentation functions.

We present first observations of the transversity parton distribution based on an analysis of pion-pair production in deep-inelastic scattering off transversely polarized targets. The extraction of transversity relies on the knowledge of dihadron fragmentation functions, which we take from electron-positron annihilation measurements. This is the first attempt to determine the transversity distribution in the framework of collinear factorization.

Supracricoid partial laryngectomy as salvage surgery for radiation therapy failure.

BACKGROUND: The main concern in the treatment of laryngeal carcinomas is tumor control with preservation of laryngeal functions. We believe that salvage supracricoid partial laryngectomy (SPL) should be carefully considered in selected cases of radiotherapy failure, because it can offer the possibility of achieving adequate tumor control with preservation of laryngeal functions. METHODS: A series of 31 patients who underwent an SPL as salvage procedure after radiotherapy failure was reviewed. RESULTS: Locoregional control rate was 75%, with 60% 5-year overall survival; no patients were lost to follow-up, and a death-from-disease rate of 19.35% was recorded. Restoration of laryngeal functions was achieved in 89.29% of the patients. No statistically significant differences were found in locoregional control regarding anterior commissure involvement, elective neck dissection versus wait-and-see policy, pathologic positive neck disease, and restage I-II versus restage III-IV. CONCLUSION: The oncologic and functional results indicate the consistency of salvage SPL, proposing this type of operation as a serious alternative to total laryngectomy in carefully selected cases.