Are statins onco- suppressive agents for every type of tumor? A systematic review of literature.

INTRODUCTION: Statins, in the role of anti-cancer agents, have been used in many types of cancers with results in some cases promising while, in others, disappointing. AREAS COVERED: The purpose of this review is to identify and highlight data from literature on the successes or failure of using statins as anti-cancer agents. We asked ourselves the following two questions:1. Could statins, which are taken mostly to reduce cardiovascular risk, guarantee a lower incidence or a better cancer disease prognosis, concerning local recurrence, metastasis or mortality?2. Does statins intake (before and/or after cancer diagnosis) improve the prognosis or increase the chemotherapeutic action when combined with other anticancer therapies? For the first question twenty-seven manuscripts have been selected, for the second one, twenty-eight. EXPERT OPINION: There are data which correlate statins with a possible tumor suppressive action among the following cancers: breast, lung, prostate and head and neck. Lastly, for gastric cancer and colorectal there is no evidence of a correlation. The onco-suppressive efficacy of statins is mainly related to the histopathological and/or molecular characteristics of the tumor cells, which have different characteristics.

Polycystic Ovary Syndrome and Alteration of Vocal Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort. METHODS: A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed. RESULTS: Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions. DISCUSSION: The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.

Reduced expression of secretogranin VGF in laryngeal squamous cell carcinoma.

Laryngeal cancer accounts for one-third of all head and neck tumors, with squamous cell carcinoma (SCC) being the most predominant type, followed by neuroendocrine tumors. Chromogranins, are commonly used as biomarkers for neuroendocrine tumors, including laryngeal cancer. It has been reported that secretogranin VGF, a member of the chromogranin family, can be also used as a significant biomarker for neuroendocrine tumors. However, the expression and role of VGF in laryngeal carcinomas have not been previously investigated. Therefore, the present study aimed to determine the expression levels of VGF in laryngeal SCC (LSCC). The present study collected tumor tissues, as well as serum samples, from a cohort of 15 patients with LSCC. The results of reverse transcription-quantitative PCR, western blot analysis and immunofluorescence assays showed that the selective VGF precursor was downregulated in patients with LSCC. Notably, in tumor tissue, the immunoreactivity for VGF was found in vimentin-positive cells, probably corresponding to T lymphocytes. The current preliminary study suggested that the reduced expression levels of VGF observed in tumor tissue and at the systemic level could sustain LSCC phenotype. Overall, VGF could be a potential biomarker for detecting neoplastic lesions with a higher risk of tumor invasiveness, even in non-neuroendocrine tumors.

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.

Partial Horizontal Supracricoid Laryngectomy: Which Factors Impact on Post-decannulation Swallowing Outcomes? A Prospective Single-Center Experience.

Early decannulation, performed within the first ten days after supracricoid partial laryngectomy, can result in a more rapid recovery of swallowing function with a semisolid bolus in the short term, about 30 days. We selected 20 patients with squamous cell carcinoma of larynx, who underwent supracricoid laryngectomies: 10 cricohyoidopexy (CHP) and 10 cricohyoidoepiglottopexy (CHEP). Staging was pT2 (10 pts), and pT3 (10 pts). Fiberoptic endoscopic evaluation of swallowing was used to assess postoperative swallowing function after a mean of 12 and 22 days from surgery. A modified PAS score (penetration-aspiration scale) was assigned for subtotal laryngectomies. Decannulation occurred after 6.7 ± 2.1 days. Univariate analysis showed that the type of surgery (CHP or CHEP), pT, resection of one arytenoid, and decannulation time are significantly associated with the 12-day PAS score. The 22-day PAS score is significantly associated with only 3 variables: type of surgery, pT, and resection of one arytenoid. From the data presented, the factors that most delay an effective recovery of swallowing are T3 and the resection of one arytenoid. Early decannulation has been shown statistically to improve PAS score in the short term, but not in the long term.

The Impact of Alcohol Consumption and Oral Microbiota on Upper Aerodigestive Tract Carcinomas: A Pilot Study.

Alcohol consumption is associated with oxidative stress and an increased risk of carcinoma of the upper aero-digestive tract (UADT). Recently, it has been found that some microorganisms in the human oral cavity may locally metabolize ethanol, forming acetaldehyde, a carcinogenic metabolite of alcohol. In a cohort of patients first visited for UADT cancers, we estimated their alcohol consumption by measuring Ethyl Glucuronide/EtG (a long-lasting metabolite of ethanol) in the hair and carbohydrate-deficient transferrin/CDT (short-term index of alcohol intake) in the serum. Moreover, we analyzed, by culture-based methods, the presence of Neisseria subflava, Streptococcus mitis, Candida albicans, and glabrata (microorganisms generating acetaldehyde) in the oral cavity. According to the EtG values, we correlated drinking alcohol with endogenous oxidative stress and the investigated microorganism's presence. We found that 55% of heavy drinkers presented microorganisms generating acetaldehyde locally. Moreover, we found that the presence of oral acetaldehyde-producing bacteria correlates with increased oxidative stress compared to patients without such bacteria. As for the study of alcohol dehydrogenase gene polymorphisms (the enzyme that transforms alcohol to acetaldehyde), we found that only the "CGTCGTCCC" haplotype was more frequent in the general population than in carcinoma patients. This pilot study suggests the importance of estimating alcohol consumption (EtG), the presence of bacteria producing acetaldehyde, and oxidative stress as risk factors for the onset of oral carcinomas.

Clinico-histopathological review of 255 patients who underwent parotidectomy for pleomorphic adenoma: a 10-year retrospective study-a proposal for an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma.

PURPOSE: Pleomorphic adenoma (mixed tumor) is the most common neoplasm of the parotid gland and one of the most frequent types of salivary gland tumor, generally with benign behavior and relatively slow growing. The adenomas could arise from the superficial, deep or from both superficial and deep parotid's lobes. METHODS: The aim of this review is to retrospectively analyze the surgical management of patients with pleomorphic adenoma of the parotid gland performed at the Department of Otorhinolaryngology (Department of Sense Organs of "Azienda Policlinico Umberto I" in Rome), from 2010 to 2020, with a focus on the percentage of recurrence and on the complication related to surgery to suggest an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma. The analysis of the complications observed in case of different surgical approaches was performed using the X2 test. RESULTS: The choice of a surgical approach (superficial parotidectomy-SP, total parotidectomy-TP, extracapsular dissection-ECD) depends on several elements, such as the location and the size of the adenoma, the availability of existing technical facilities and the professional experience of the surgeon. A transient facial palsy was present in 37.6%, 2.7% reported a permanent facial nerve palsy, 1.6% developed a salivary fistula, 1.6% a post-operative bleeding and 2.3% showed Frey Syndrome. CONCLUSION: The surgical management of this benign lesion is required, even in asymptomatic cases, to prevent the progressive growing and to reduce the risk of malignant transformation. The goal of surgical excision is to obtain the complete resection to minimize the risk of tumor recurrence and avoiding facial nerve disability. Therefore, an accurate preoperative study of the lesion and the choice of the most appropriate surgical treatment are essential to minimize the rate of recurrence.

The Impact of the COVID-19 Pandemic on the Prognosis of Laryngeal Adenoid Cystic Carcinoma: A Case Report and a Literature Review.

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

SMN Deficiency Destabilizes ABCA1 Expression in Human Fibroblasts: Novel Insights in Pathophysiology of Spinal Muscular Atrophy.

The deficiency of survival motor neuron protein (SMN) causes spinal muscular atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma membrane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

Surgical Approach to Frontal and Ethmoid Sinus Osteomas: The Experience of 2 Metropolitan Italian Hospitals.

OBJECTIVES: The aim of this study was to report the surgical management experience of patients with osteomas of the frontal and ethmoid sinuses performed in 2 metropolitan Italian hospitals between 2012 and 2019. METHODS: A retrospective chart review of cases of frontal and ethmoid osteomas from the Ca' Granda Niguarda Hospital of Milan and the Policlinico Umberto I University Hospital of Rome was performed. All patients underwent preoperative computed tomography and, when orbital or intracranial extension was suspected, magnetic resonance imaging. Surgical treatment was performed according to Chiu classification. RESULTS: A total of 38 cases of frontal and ethmoid sinus osteomas were included in the study; 22 patients were men and 16 were women. The mean age at diagnosis was 49 years. Seven (18.4%) patients were treated using an open approach; 3 (7.9%) patients underwent open and endoscopic approach; the remaining 28 (73.7%) patients were treated with endoscopic approach. Seven (18.4%) patients had a cerebrospinal fluid leak intraoperatively and were treated with the placement of tissue graft through the defect. The mean follow-up time was 18 months; no recurrence was observed at 12-month follow-up. CONCLUSION: Osteomas of the frontal and ethmoid sinuses can be treated using different techniques, mostly endoscopically. The choice of surgical approach (endoscopic vs open) depends on the location and size of the osteoma, anatomical size, characteristic of the sinus, surgeon's experience, and available existing technical facilities. Cerebrospinal fluid leak is a possible complication of surgery.

Extraneural Sclerosing Perineurioma of the Tongue.

Perineurioma (PN) is an uncommon benign peripheral nerve sheath tumor. For the rarity of this tumor in the oral cavity, otolaryngologists and oral surgeons might not be familiar with this entity. Perineuriomas are typically benign and complete excision is deemed adequate management. Thus, their histological recognition is mandatory to avoid unnecessary overtreatment. We report the clinicopathologic findings of an uncommon variant, the Extraneural Sclerosing PN, in an unusual and never described site, the tongue.

A Rare Case of Extracranial Schwannoma of the Hypoglossal Nerve Located in the Parapharyngeal Space Mimicking a Deep Neck Abscess.

Schwannomas are neurogenic benign tumors originating from the myelin sheath of peripheral nerves, and hypoglossal Schwannomas account for 5% of nonvestibular ones. Extracranial localizations are substantially rare, especially those affecting exclusively the parapharyngeal space; for this reason, the retrostyloid neoformations could initially masquerade as a carotid tumor or deep organized neck abscess. The purpose of this report is to highlight the importance of a multidisciplinary approach in the correct management of differential diagnosis.

A New Montgomery® Salivary Bypass Tube Placement Technique: Report of Procedures Performed on Patients With Tracheoesophageal Fistula or Pharyngoesophageal Stenosis.

Salivary Bypass Tube is an important tool to prevent or treat some complications of laryngeal and hypopharyngeal surgery and its placement may prove difficult. In this article, we propose a new technique to simplify its management by using an Oral/Nasal Tracheal Tube Cuffed-Reinforced that allowed us to reduce operating times, complications related to prolonged general anesthesia, and the traumas on the tissues incurred during the forced positioning of the device with standard techniques.

Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies.

Aberrant expression of the programmed cell death protein ligand 1 (PD-L1) constitutes one of the main immune evasion mechanisms of cancer cells. The approval of drugs against the PD-1-PD-L1 axis has given new impetus to the chemo-therapy of many malignancies. We performed a literature review from 1992 to August 2022, summarizing evidence regarding molecular structures, physiological and pathological roles, mechanisms of PD-L1 overexpression, and immunotherapy evasion. Furthermore, we summarized the studies concerning head and neck squamous cell carcinomas (HNSCC) immunotherapy and the prospects for improving the associated outcomes, such as identifying treatment response biomarkers, new pharmacological combinations, and new molecules. PD-L1 overexpression can occur via four mechanisms: genetic modifications; inflammatory signaling; oncogenic pathways; microRNA or protein-level regulation. Four molecular mechanisms of resistance to immunotherapy have been identified: tumor cell adaptation; changes in T-cell function or proliferation; alterations of the tumor microenvironment; alternative immunological checkpoints. Immunotherapy was indeed shown to be superior to traditional chemotherapy in locally advanced/recurrent/metastatic HNSCC treatments.

Surgical Excision of Unusual Sacked Neck and Mediastinum Abscess of Odontogenic Origin.

The most common cause of neck infections is odontogenic abscesses that can often be life-threatening and require a surgical drain associated with antibiotic therapy. We present a case of the surgical management of an odontogenic sack-shaped and walled abscess arising from elements 3.6, 3.7 and 3.8 that reached the laterocervical spaces and anterior mediastinum in a 28-year-old healthy woman. Typical signs and symptoms of cervical complications of dental origin are fever, a neck mass, lymphadenopathy, trismus and odynophagia. The gold standard treatment in these situations is a multidisciplinary approach involving an oral surgeon, ENT specialist and thoracic surgeon to drain the infected material. To the best of our knowledge, this is the first described case report of a dental abscess enclosed in a sack in the deep space of the neck and in the anterior space of the mediastinum.

Systematic Review of Parotid Gland Sarcomas: Multi-Variate Analysis of Clinicopathologic Findings, Therapeutic Approaches and Oncological Outcomes That Affect Survival Rate.

The aim of this study was to systematically review the literature of sarcoma of the parotid gland in order to analyze the main factors affecting survival rate. A systematic literature review was performed between January 1990 to November 2021, and 88 patients affected by parotid gland sarcomas were included. The most common histological types were Rhabdomyosarcoma and Synovial Sarcoma. From our review, it emerges that primary sarcomas of the parotid glands are locally aggressive but show low tendency to metastasize to the lymph nodes of the neck and that surgery (i.e., total or radical parotidectomy) is the main approach for their treatment. The global overall survival (OS) is 52% at 5 years and 34.1% at 10 years. The OS for T1, T2, T3, T4 tumor at 5 years of follow up is 80.0%, 66.5%, 56.7% and 33.3%, respectively. Size/extension at the diagnosis and the sarcoma's histotype are the most important prognostic factors. Multivariate analysis showed that surgery (total or radical parotidectomy) performed on the tumor (p = 0.0008) was the only parameter that significantly affected the OS. Among the other variables, age (younger), use of adjuvant therapy and lymph node metastasis showed borderline significative values (p = 0.05). Our analysis suggests that, when a primitive parotid sarcoma is diagnosed, total or radical parotidectomy should be performed at any age independent of tumor histology. Because regional lymph node metastases from parotid sarcomas are uncommon, alternative strategies (e.g., close follow-up by imaging and evaluation of sentinel lymph nodes) should be pursued before lymph node (selective/radical) dissection.

Sudden Sensorineural Hearing Loss after Third Dose Booster of COVID-19 Vaccine Administration.

Coronavirus disease 2019 (COVID-19) was declared a pandemic due to its rapid spread worldwide, and its vaccination campaign is considered one of the most historic public hygiene measures in modern medicine. Sudden sensorineural hearing loss (SSHL) is a common emergency that affects patient's quality of life and requires rapid treatment with steroids. The etiology could be viral or vascular even though in most cases it remains unknown (idiopathic SSHL). During the SARS-CoV-2 vaccination campaign, several rare but serious adverse events have been reported including thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré Syndrome. ENT adverse events after vaccination were reported too, including cases of sudden sensorineural hearing loss (SSHL), vestibular neuronitis and audio vestibular disorders (such as tinnitus, dizziness, and vertigo). For the first time here, we reported two cases of SSHL after third administration of COVID-19 mRNA vaccine. Even if there is not clear evidence of an association between SSHL and vaccination, adverse effects should be kept in mind since viral infection could be the etiology of SSHL.