Oral and oropharyngeal malignant minor salivary gland tumors: A retrospective study.

INTRODUCTION: Tumors of minor salivary gland origin are uncommon lesions, representing 2-3 % of all malignant neoplasms of the upper aerodigestive tract and 9-23 % of all salivary gland tumors. The aim of this study is to report the demographic features, sites, histological types and the management and outcomes of oral and oropharyngeal minor salivary gland tumors diagnosed and treated in a University Hospital with a multidisciplinary head and neck team. MATERIALS AND METHODS: A single-center retrospective observational study was conducted in a cohort of patients who received diagnosis of minor salivary gland carcinoma of oropharynx and oral cavity between July 30th 2000 and 30th September 2021. The following data of the included patients were collected: age, gender, smoke history, alcohol consumption, past medical history, comorbidities, anatomic location of the tumor, histopathology, staging, management, and outcomes. RESULTS: A total of 30 cases (16 females, 14 males) of oral and oropharyngeal minor salivary gland tumors were reviewed. The most frequent histotype was polymorphous adenocarcinoma (12 patients). The majority of patients presented with low stage at diagnosis, with 66,66 % of the population classified as stage I or II at diagnosis. On the whole, 29 patients out of 30 benefitted from a surgical approach as first treatment. In 11 patients, adjuvant radiotherapy was performed and in 6 cases it was associated with chemotherapy. Brachytherapy with different timing was performed in 5 cases. The recurrence rate was 26.66 %. Overall disease specific survival at five and ten years was found to be approximately 81 % and 33 % respectively. CONCLUSIONS: Surgery is still considered to be the gold standard of the treatment of minor salivary gland tumors. Radiation therapy, in spite of not being considered as a curative primary treatment for salivary malignancies, is extensively used as an adjuvant treatment.

Machine Learning Model as a Useful Tool for Prediction of Thyroid Nodules Histology, Aggressiveness and Treatment-Related Complications.

Thyroid nodules are very common, 5-15% of which are malignant. Despite the low mortality rate of well-differentiated thyroid cancer, some variants may behave aggressively, making nodule differentiation mandatory. Ultrasound and fine-needle aspiration biopsy are simple, safe, cost-effective and accurate diagnostic tools, but have some potential limits. Recently, machine learning (ML) approaches have been successfully applied to healthcare datasets to predict the outcomes of surgical procedures. The aim of this work is the application of ML to predict tumor histology (HIS), aggressiveness and post-surgical complications in thyroid patients. This retrospective study was conducted at the ENT Division of Eastern Piedmont University, Novara (Italy), and reported data about 1218 patients who underwent surgery between January 2006 and December 2018. For each patient, general information, HIS and outcomes are reported. For each prediction task, we trained ML models on pre-surgery features alone as well as on both pre- and post-surgery data. The ML pipeline included data cleaning, oversampling to deal with unbalanced datasets and exploration of hyper-parameter space for random forest models, testing their stability and ranking feature importance. The main results are (i) the construction of a rich, hand-curated, open dataset including pre- and post-surgery features (ii) the development of accurate yet explainable ML models. Results highlight pre-screening as the most important feature to predict HIS and aggressiveness, and that, in our population, having an out-of-range (Low) fT3 dosage at pre-operative examination is strongly associated with a higher aggressiveness of the disease. Our work shows how ML models can find patterns in thyroid patient data and could support clinicians to refine diagnostic tools and improve their accuracy.

Clinical and Prognostic Implications of Cervical and Ocular Vestibular Evoked Myogenic Potentials (cVEMP and oVEMP) in Benign Paroxysmal Positional Vertigo (BPPV): A Prospective Study.

OBJECTIVE: Several studies have investigated the efficacy of VEMP (vestibular evoked myogenic potential) in patients with vestibular disorders and BPPV (benign paroxysmal positional vertigo). However, previous data were inconclusive. The aim of this study was to investigate the difference in latency, amplitude P1-N1, asymmetry ratio (AR), and cervical/ocular-VEMP values between BPPV patients and healthy controls. METHODS: 125 healthy subjects and 42 BPPV patients were prospectively enrolled in the study. In both groups, c/oVEMP tests with 500 Hz tone-burst stimuli were performed. Latencies P1, N1 peaks, and corrected amplitudes (CA) were measured, and AR was calculated. RESULTS: in the BPPV group, 14.29% of patients lacked oVEMPs that recovered after therapy. N1 latencies were significantly elongated, and 50% of patients had pathological AR; this value normalized at follow-up sessions. In addition, there was a reduction in CA in the pathologic ear compared to healthy ears (p = 0.04) and compared to healthy controls (p = 0.01). For cVEMP, a significant reduction in latency-P1 was observed in BPPV patients compared to controls; no significant differences were observed for P1, N1, and CA values between the two ears. The cVEMPs were absent in 14.29% of BPPV patients (AR > 35) that recovered after therapy. CONCLUSION: We identified several abnormal c/oVemp values in BPPV patients compared with healthy controls, with most changes in values occurring in oVEMPs, suggesting that utricular dysfunction may be more common than saccular. In addition, patients with oVEMP alteration showed later clinical recovery, suggesting a possible prognostic role of the test.

Parapharyngeal Metastasis of Papillary Carcinoma of Thyroid Gland: A Case Report and a Review of the Literature.

Papillary carcinoma is the most frequently encountered differentiated thyroid carcinoma. Usually, metastasis occurs along lymphatic pathways in the central compartment and along the jugular chain. Nevertheless, lymph node metastasis in the parapharyngeal space (PS) is a rare but possible event. In fact, a lymphatic pathway has been identified that connects the upper pole of the thyroid and the PS. We describe the case of a 45-year-old man with a two-month history of a right neck mass. He underwent a complete diagnostic path that highlighted the presence of a parapharyngeal mass associated with the presence of a thyroid nodule suspected to be malignant. The patient underwent surgery (thyroidectomy and removal of the PS mass that was found to be a metastatic node of papillary thyroid carcinoma). The aim of this case is to underline the importance of detecting these kinds of lesions. Nodal metastasis in PS from thyroid cancer is a rare occurrence that is not easily detectable by a clinical examination until the metastasis reaches a considerable dimension. Computed tomography (CT) and magnetic resonance imaging (MRI) permit early identification, but unfortunately, these are not usually employed as a first-level imaging technique in patients with thyroid cancer. The treatment of choice is surgery with a transcervical approach that allows for better control of the disease and of the anatomical structures. Non-surgical treatments are usually reserved for patients with advanced disease, with satisfactory results.

A solitary sinonasal angiomatous polyp presenting with obstructive sleep apnea in an adult.

BACKGROUND: Obstructive sleep apnea (OSA) is frequently encountered in adult sleep disorders and needs careful differential diagnosis.Ear, nose, throat examination, including naso-laryngeal endoscopy, is mandatory in all cases to rule out potential obstructing lesions causing OSA. CLINICAL PRESENTATION: This report presents a 64-year-old male with snoring, nasal blockage (especially during night-time), and mild OSA. Physical-examination and CT revealed a unilateral vascularized left sinonasal mass extending to the nasopharynx and protruding into the oropharynx during inhalation. Due to suspicions of malignancy or vascular tumor, the patient also underwent contrast MRI. Endoscopic surgery was performed, and the final diagnosis was a sinonasal angiomatous polyp (SAP). SAPs are rare, and this is the first reported case of an adult solitary unilateral angiomatous polyp referral for OSA. CONCLUSION: Nasal masses need to be considered in the differential diagnosis of patients with obstructive sleep disorders in order to avoid wrong or ineffective treatment.

Does Prolonged FFP2 Mask Use Cause Changes in Nasal Cytology? A Pilot Observational Study on Healthcare Workers.

TheCOVID-19 pandemic has rapidly spread worldwide. Individual prevention approaches include FFP2/N95 mask use. Healthcare (HC) workers wear face masks for a long time during their work shifts and often complain of nasal symptoms. Current data on mask-associated symptoms or upper airway epithelium transformations are limited. Nasal cytology (NC) is a useful, non-invasive diagnostic method to assess cellular alterations. The aim of this study is to compare NC in HC workers before and after the continuous wearing of FFP2 face masks. We conducted a pilot observational study on 10 volunteer HC workers, who continuously used FFP2 masks during the work shift. All subjects underwent NC at the beginning (T0) and at the end of their workshift (T1) and the cytological findings were compared. Moreover, nasal symptoms were collected. Rare inflammatory cells were detected at T0 and, comparing cytological data about T0 and T1, no significant differences were observed. The most reported nasal symptoms were itching (70%) and a dry nose (60%). Difficulty of breathing and nasal blockage were not relevant. These preliminary data seem to suggest that wearing an FFP2 mask does not determine observable alterations in NC in daily work. However, further studies on a larger population for a longer period are needed.

Prophylactic central neck dissection in differentiated thyroid cancer: risks and benefits in a population with a high rate of tumour recurrence.

BACKGROUND: The role of prophylactic central neck dissection (pCND) in differentiated thyroid cancer (DTC) is still controversial. METHODS: In a cohort of 274 DTC cN0 patients with a high rate of tumour recurrence, who underwent total thyroidectomy with or without pCND, clinical and histopathological features were retrospectively analysed. RESULTS: In our cohort, no clinical or histopathological features are able to predict the presence of central lymph node metastases (CLNM) at diagnosis, which instead represents the only variable significantly associated with a higher risk of long-term tumour relapse, independently from age, sex, BMI and radioiodine treatment (OR=1.03, CI95% 1.002-1.074, p<0.05). Moreover, our study demonstrates that pCND does not significantly increase the risk of post-surgical complications. CONCLUSIONS: In our setting, pCND could have a key role in the management of DTC. The risks and benefits of pCND should be evaluated for each population to make the most appropriate therapeutic choice.

Respiratory presentation of diffuse idiopathic skeletal hyperostosis (DISH): Management and review of the literature.

Background: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by the ossification of entheses. When localized in the cervical paravertebral region, typical signs and symptoms include stiffness, pain, loss of range of motion, and difficulty swallowing.Clinical Presentation: The authors present two less typical respiratory manifestations of DISH due to cervical osteophytes protrusion and obstruction of the upper airway. The first patient was treated conservatively (application of CPAP during nighttime), while the second required emergency intubation and a combined ENT-neurosurgical operation for the removal of osteophytes.Clinical Relevance: Even though dysphagic symptoms are more frequent, DISH may be a cause of airway obstruction and should be included in the differential diagnosis of respiratory distress and OSA.

Variation in Body Mass and Skeletal Muscle Indices in Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy and Nutritional Intervention.

The aim of this study was to analyze variation in body mass index (BMI) and skeletal muscle index (SMI) in head and neck squamous cell carcinoma (HNSCC) patients who underwent exclusive radiotherapy (RT) or concurrent chemo-radiotherapy (RT-CHT). We enrolled 73 HNSCC pts treated with definitive or post-operative RT (14 pts) or RT-CHT (59 pts). At the time of diagnosis (t0) and 3 months after treatment completion (t3), CT scans were retrieved to measure skeletal muscle at the level of the C3 vertebra. Median follow-up was 16 months. Nine disease progressions with distant metastases and eleven local relapses were observed. Fifty-three pts were free from progression at 1 year. At t0, average BMI was 25.8 (SD 4.1), while at t3 it was 24.5, with no reduction in 54 pts. A BMI decrease of −1.3 (p-value < 0.0001) between t0 and t3 was found with the Wilcoxon signed-rank test. SMI was 57.1 and 59.2 at t0 and t3, respectively (p-value = 0.005). According to our analysis, SMI variation seems to reflect the effect of an appropriate nutritional intervention and may represent a reliable, simple tool for muscle mass analysis.

Simple Parameters from Complete Blood Count Predict In-Hospital Mortality in COVID-19.

INTRODUCTION: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. MATERIALS AND METHODS: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. RESULTS: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio (χ 2 7.6; p = 0.006), and platelet count (χ 2 5.39; p = 0.02), along with age (χ 2 87.6; p < 0.001) and gender (χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/µL was, conversely, protective (OR: 0.45 (0.32-0.63)). CONCLUSION: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Macrophages expressing TREM-1 are involved in the progression of HPV16-related oropharyngeal squamous cell carcinoma.

INTRODUCTION: Many types of research have been performed to improve the diagnosis, therapy, and prognosis of oropharyngeal carcinomas (OP-SCCs). Since they arise in lymphoid-rich areas and intense lymphocytic infiltration has been related to a better prognosis, a TREM-1 putative function in tumour progression and survival has been hypothesized. MATERIALS AND METHODS: Twenty-seven human papillomavirus (HPV) 16+ OP-SCC specimens have been analyzed to relate TREM-1 expression with histiocytic and lymphocytic markers, HPV presence and patients' outcome. RESULTS: No differences have been shown between intratumoral and stromal CD4+ cells, while intratumoral CD8+ lymphocytes are higher with respect to the tumour stroma (p = .0005). CD68+ cells are more than CD35+ and TREM-1+; their presence is related to CD35± and TREM-1± histiocytes (p = .005 and .026, respectively). Intratumoral CD4+ lymphocytes are higher in p16+ cases (11/27) than in p16- (p = .042); moreover, p16 positivity correlates to a better survival (p = .034). CD4+, CD8+ and CD35+ cells have no impact on survival, while CD68 expression heavily influences progression and bad outcome (p = .037). TREM-1 positivity also leads to worst overall survival (p = .001): peritumoral expression and death-cause relationship are always significant, particularly when the cause is OP-SCC (p = .000). CONCLUSION: While p16 shows to better stratify HPV16+ patients' outcome, TREM-1+ macrophages suggest their key importance in HPV-related OP-SCCs progression.KEY MESSAGESTREM-1 positivity correlates to the worst overall survival of HPV16-positive OPSCCs-affected patients.p16-positive HPV16 related OPSCCs patients have a better prognosis with respect to p16-negative ones.

Nasal Cytology in Radiofrequency Turbinate Volume Reduction.

INTRODUCTION: Radiofrequency turbinate volume reduction (RFTVR) is an effective treatment of inferior turbinate hypertrophy. RFTVR can reduce epithelial cell alterations in nasal mucosa. The aim of this observational study was to evaluate the effects of RFTVR on nasal obstruction and cytology, stratifying for different types of rhinitis. METHODS: Nasal cytology and subjective nasal obstruction were evaluated on 113 patients before RFTVR (T0) and after 3 months (T1). The patients were divided into groups on the basis of the underlying disease: allergic rhinitis, nonallergic rhinitis, rhinitis medicamentosa, and other diseases (e.g., hormonal-based turbinate hypertrophy). RESULTS: Nasal cytology at T0 identified 42 patients with allergic rhinitis, 40 with nonallergic rhinitis, 19 with rhinitis medicamentosa, and 12 with other diseases. An improvement of nasal cytology at T1 was observed in 29.2% of cases. They mainly consisted of patients with nonallergic rhinitis with neutrophils, whose neutrophil infiltrate decreased. Only 2 cases (1.7%) showed a worsening of nasal cytology at T1. A statistically significant decrease in subjective nasal obstruction was observed for every group (p < 0.05). Higher differences of nasal obstruction between T0 and T1 were found in patients with rhinitis medicamentosa or other diseases. CONCLUSION: RFTVR represents a safe and effective treatment for turbinate hypertrophy of various etiology. It is not responsible for a worsening of inflammatory infiltrate of the nasal mucosa.

Oral microbiota and vitamin D impact on oropharyngeal squamous cell carcinogenesis: a narrative literature review.

An emerging body of research is revealing the microbiota pivotal involvement in determining the health or disease state of several human niches, and that of vitamin D also in extra-skeletal regions. Nevertheless, much of the oral microbiota and vitamin D reciprocal impact in oropharyngeal squamous cell carcinogenesis (OPSCC) is still mostly unknown. On this premise, starting from an in-depth scientific bibliographic analysis, this narrative literature review aims to show a detailed view of the state of the art on their contribution in the pathogenesis of this cancer type. Significant differences in the oral microbiota species quantity and quality have been detected in OPSCC-affected patients; in particular, mainly high-risk human papillomaviruses (HR-HPVs), Fusobacterium nucleatum, Porphyromonas gingivalis, Pseudomonas aeruginosa, and Candida spp. seem to be highly represented. Vitamin D prevents and fights infections promoted by the above identified pathogens, thus confirming its homeostatic function on the microbiota balance. However, its antimicrobial and antitumoral actions, well-described for the gut, have not been fully documented for the oropharynx yet. Deeper investigations of the mechanisms that link vitamin D levels, oral microbial diversity and inflammatory processes will lead to a better definition of OPSCC risk factors for the optimization of specific prevention and treatment strategies.

AKR1C3 is a biomarker and druggable target for oropharyngeal tumors.

PURPOSE: Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets. METHODS: 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects. RESULTS: Gene set enrichment analysis (GSEA) on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels. CONCLUSIONS: We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.

Molecular characterisation and clinical correlation of papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (mPTC) is defined as a papillary thyroid cancer sized 10 mm or less. Despite their generally indolent clinical course and good prognosis, a subset of mPTCs shows potentially aggressive behaviour. METHODS: To search for predictors of clinical outcome of mPTCs, we retrospectively evaluated the genetic tumour profile of 100 patients (23 M/77 F, mean age ± SD 53.8 ± 13.4 years) with histologically confirmed mPTCs through analysis of BRAF, NRAS and TERT promoter mutations as well as RET/PTC translocations. RESULTS: Mean follow-up period was 8.4 ± 3.6 years. In 55 cases, mPTC were detected incidentally after surgery. Capsular invasion, bilateralism and multifocality were found in 11/100, 17/100 and 24/100 cases, respectively, while lymph-nodes metastases were present at diagnosis in 9/100 cases. After 3.5 ± 2.0 years, tumour relapse occurred in 6/100 cases and was locoregional in five (two in the thyroid bed, three in laterocervical lymph-nodes), while lung metastasis occurred in one case. Biochemical persistence of disease was seen in 1/100 case. Mutations occurred in 55/100 cases; BRAFV600E was the most frequently detected (49/100) and was associated with higher tumour size, bilateralism and follicular variant but not with capsular invasion. RET/PTC rearrangements were found in 2/100 cases, NRASQ61R in 4/100, while no mutations of TERT promoter gene were detected. Despite the observed association between BRAFV600E mutation and unfavourable histopathological features, we found no direct association with tumour recurrence, distant metastases and mortality. CONCLUSION: In our study, the search for the most frequent genetic alterations as prognostic markers in mPTCs would not have changed the therapeutic strategy.

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Smell and taste disorders during COVID-19 outbreak: Cross-sectional study on 355 patients.

BACKGROUND: As reported by increasing literature, a significant number of patients with SARS-CoV-2 infection developed smell/taste disorders. Aim of this study is to determine the prevalence and severity of these symptoms among laboratory-confirmed SARS-CoV-2 patients. Secondary objective is to determine their onset/recovery time. METHODS: This cross-sectional study was conducted from March 10 to 30, 2020 at Novara University Hospital during the COVID-19 Italian outbreak. The 355 enrolled patients answered a questionnaire at 14th (or more) days after proven infection. RESULTS: The overall population prevalence of both smell/taste or one of the two disorders was 70%. They were first symptoms in 31 (8,7%) patients. Most patients reported a complete loss that in half of the cases (49.5%) was fully recovered after 14 days, with a median recovery time of 10 days. CONCLUSION: This study confirms a high prevalence of smell/taste disorders in COVID-19 infection with self-recovery for half cases after about 2 weeks.