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.

Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Influence of Prior Endoscopic Sinus Surgery Extent on Dupilumab Effectiveness in CRSwNP Patients.

BACKGROUND: Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab. MATERIALS AND METHODS: This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated. RESULTS: A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores. CONCLUSION: Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1556-1563, 2024.

Chronic Rhinosinusitis with Nasal Polyps: A Survey on Routine Management and Evaluation of Disease Control in Practice.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a significant impact on quality of life. The overall goal of CRSwNP management, as with other chronic conditions, is to achieve "disease control", and for that reason, a definition of control of disease is pivotal in deciding the best treatment strategy. Although many staging systems have already been developed to evaluate the disease, disease control is not yet to be standardized, and a specific tool that is consistently applied and accepted by all practitioners is still missing in daily clinical practice. To gain an overview of the implementation and limitations of existing guidelines and to shed light on real-life definitions of control and disease severity, we conducted a nationwide survey of otorhinolaryngologists routinely treating CRSwNP to identify unmet clinical needs in Italy. The results showed homogeneous responses regarding the knowledge contained in international guidelines while highlighting the difficulty of their implementation in day-to-day practice. Respondents called attention to the importance of clinical symptoms, giving more weight to the patient's perspective. Among the symptoms to be considered, respondents emphasized nasal obstruction, followed by loss of sense of smell and rhinorrhea. Others also believe that the physician's perspective should be considered, and the inclusion of endoscopy as a measure of control was warranted by many. The need for a specific tool that is able to unequivocally ascertain disease control is increasingly pivotal in this new era of biologics for treating CRSwNP.

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.

Patient's Scar Satisfaction after Conventional Thyroidectomy for Differentiated Thyroid Cancer.

Differentiated thyroid carcinoma (DTC) is the most frequent endocrine neoplasm. Its treatment is based on surgery with consequent impact on patients' quality of life (QoL) and aesthetic implication. The aim of the present study is to assess scar satisfaction in patients affected by DTC who underwent total or partial thyroidectomy. A comparison was also made between scar satisfaction with different subcuticular suture. Validated questionnaires have been employed during a 3-month follow-up: Patient and Observer Scar Assessment Scale (POSAS) and the Patient Scar Assessment Questionnaire (PSAQ). Eventually, the impact of thyroid cancer on QoL of patients was performed in the studied population employing the Thyroid-related patient-reported outcome questionnaire (ThyPRO) and European Organisation for Research Additionally, Treatment of Cancer-Quality of Life questionnaire-C30 (EORTC QLQ-C30). It was conducted in a single center observational study considering 74 patients respecting inclusion criteria. Overall scar satisfaction was found to improve during follow-up, reaching the best scores at 3 months from surgery. Subcuticular suture does not seem to influence the scar satisfaction. In our study male patients seem to be more satisfied, on the other hand age does not seem to influence satisfaction. Overall, the ThyPRO questionnaire and EORTC QLQ-C30 scores did not statistically differ between preoperative and postoperative suggesting a small impact of DTC in QoL.

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.

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. METHODS: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. RESULTS: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. CONCLUSIONS: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell.

Practical recommendations for managing severe chronic rhinosinusitis with nasal polyps in the era of biologics.

Objective: We conducted a national survey to understand how rhinology practice has changed with the advent of biologics and how this affected patients with uncontrolled, severe chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to analyse the results of the survey and infer practical recommendations for clinical practice. Methods: A group of ear, nose, and throat specialists (ENTs) experienced in the management of CRSwNP developed a 74-question survey. ENTs from rhinology centres authorised to prescribe biologics in the context of the national health system were invited to answer it between 01/05/2022 and 31/07/2022. The responses underwent descriptive analyses, and the authors discussed the results and derived practical recommendations for clinical practice. Results: ENTs working in rhinology centres changed their practices coinciding with the advent of biologics. CRSwNP evaluations have become more complex because they involve diagnostic confirmation, determining the patients' immunologic profile, and other factors. We observed heterogenous behaviours in practice that may be conditioned by the novelty of the topic. The results of the survey were used to develop practical recommendations for ENTs and are summarised herein. Conclusions: Clinical practice in rhinology outpatient clinics has changed profoundly in the era of biologics. Our practical recommendations for clinicians working in rhinology centres are expected to help standardise practice and improve care.

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.

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.

Survey on Use of Local and Systemic Corticosteroids in the Management of Chronic Rhinosinusitis with Nasal Polyps: Identification of Unmet Clinical Needs.

Background: Local and systemic corticosteroids have long been the workhorse in management of chronic rhinosinusitis with nasal polyps (CRSwNP), although there is no universally accepted modality of prescription. We carried out a survey in Italy to capture current trends in the use of topical and systemic corticosteroids in patients with CRSwNP. Methods: A survey was set up on Survey Monkey®. Each author distributed the link to the survey in an ad hoc manner and a total of 437 participants filled out the survey. Results: Mometasone furoate (79.3%) was the most frequently prescribed, administered daily by 61.9% of participants; the remaining preferred to discontinue treatment for brief periods to reduce side effects or to modulate the therapy in mild cases. The majority believe that a short cycle of systemic steroids should be prescribed for re-exacerbation of symptoms and that the number of cycles in the previous year should be evaluated to define control of the disease even if international guidelines do not provide clear indications on this topic. A certain degree of divergence emerged from responses regarding how long and the maximal dose of systemic steroids which place patients at high risk for adverse events. Finally, systemic corticosteroids seem to offer only temporary benefit on recovery of smell without guaranteeing long-term control even if the patient is adherent to topical corticosteroids. Conclusions: Our results highlight the need for clear guidelines on oral steroids, which could help supporting the use of a precision medicine approach, including indications for new biological agents.

Inducible T-cell co-stimulator (ICOS) and ICOS ligand are novel players in the multiple-myeloma microenvironment.

The inducible T-cell co-stimulator (ICOS) is a T-cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B-cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte-bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie-Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL+ MOPC-21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM.

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.

Paraganglioma of the Thyroid Gland: A Case Report and a Review of the Literature.

Paragangliomas of the thyroid gland are rare and usually they originate from the inferior laryngeal paraganglia. In this case report, we describe the case of a 78-year-old woman who presented with an incidental finding of thyroid nodule dislocating the trachea. After a systemic and radiological evaluation, right lobo-isthmectomy was performed, and the definitive diagnosis of paraganglioma was reached. Diagnosis of these thyroidal lesions could be difficult due to their rarity, to their specific radiological aspects and the need of employing specific histological staining techniques. Once the definitive diagnosis is reached, patients should undergo a systemic and genetic evaluation. Surgery is the gold standard treatment; radiotherapy should be considered when aggressive behavior is suspected. Regular long-lasting follow-up should be proposed to these patients considering the unpredictable behavior of these lesions.

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.

The various meanings and imperfections of words.

In this reply to a letter, the Authors discuss the raised points regarding the nomenclature and management of Lymphatic Malformations / Lymphangiomas.