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Purpose of ReviewThe treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease’s control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC.Recent FindingsWe categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease’s control and survival.SummaryConsidering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.

Background Recently, many studies have investigated the role of tumor immune microenvironment (TIME) in carcinogenesis, highlighting its relation to both tumor regression and progression. In particular, the “inflammatory system”, made of innate and adaptive immune cells, interacts with cancer cells and their surrounding stroma. In this setting, the aim of this review is to summarize the current literature regarding the TIME of major salivary gland carcinomas (MSGCs), with particular attention on the characteristics and prognostic role of tumor infiltrating lymphocytes (TILs), the mechanisms that lead to TILs exhaustion and the important additional immune infiltrating factors that help SGC progression or remission. Methods A comprehensive literature search was performed concerning published articles on the role of TIME in MSGCs. Results In this work we summarize the advancing knowledge on TIME in SGCs by demonstrating the key prognostic and/or predictive value of specific immune features. Conclusion From the analysis of the current ‘status of the art’ it clearly emerges a need for precise, unambiguous phenotyping of immune cell populations, as well as a more thorough understanding of the frequencies and interactions of multiple immune cell types inside the TIME and their spatial localization (intratumoral vs. stromal).

Purpose Our study aimed to describe recovery of gustatory dysfunction (GD) and olfactory dysfunction (OD) in COVID-19 patients, and to analyze variables associated with early or late recovery. Methods Telephone surveys were administered during an 18-month follow-up after COVID-19 diagnosis. One hundred and thirty-two included patients rated olfactory and gustatory function at each follow-up. Results One hundred and twenty-nine patients reported GD, of whom 91 (70.5%) reported severe GD, and 99 patients reported OD, of whom 84 (84.9%) reported severe OD. Seventy-two/129 (55.8%) and 52/99 (52.5%) patients reported an improvement in GD and in OD during the first 7 days from the onset, respectively. At 3-month follow-up, 110/120 patients (85.3%) recovered from GD, while 80/99 patients (80.8%) recovered from OD. At 18-month follow-up, a total of 120/129 patients (93.0%) recovered from GD and 86/99 patients (86.9%) recovered from OD; while 10 patients (7.0%) still reported GD and 13 patients (13.1%) still reported OD. Severe GD/OD at presentation were associated with late complete recovery of taste/smell ( p  = 0.019 and p  = 0.034, respectively). Improvement over the first 7 days from onset was significantly associated with faster recovery ( p  < 0.001). Conclusions More than 80% of patients reported complete recovery of olfactory/gustatory function in the first 3 months after symptom onset. At 18-month follow-up, patients reporting complete recovery of gustatory and olfactory function were 93% and 87%, respectively. Severity of chemosensory dysfunction at the onset was negatively correlated to recovery, and improvement of taste and/or smell function within the first 7 days from symptom onset was significantly associated with early resolution.

Objectives: Medullary thyroid carcinoma (MTC) is a rare but biologically aggressive neuroendocrine tumor for which reliable preoperative prognostic biomarkers are still lacking. This study aimed to evaluate the association between preoperative blood immunological markers and disease recurrence in patients with MTC undergoing curative surgery. Methods: We conducted a retrospective cohort study at a single tertiary academic center including 52 consecutive patients who underwent curative surgery for MTC between January 1999 and December 2023. The study size was determined by including all eligible consecutive patients meeting predefined inclusion/exclusion criteria within the study period. Preoperative inflammatory indices (MLR, NLR, PLR, SII, SIRI) were calculated from standardized complete blood count tests performed within 30 days before surgery. Disease-free survival (DFS) was calculated using the Kaplan–Meier method. Cox proportional hazards regression analysis with a backward stepwise selection based on the Akaike Information Criterion was used to identify independent predictors of recurrence, adjusting for potential confounders. Results: The mean age was 55.0 years (range 31–75), and 73% of patients were female. The ROC-derived cut-off for preCT was 181 pg/mL. Locally advanced disease (T3-T4) was observed in 12% of cases, and cervical node metastases in 27%. With a mean follow-up of 75.48 months, the 3- and 5-year DFS rates were 91% and 86%, respectively. On multivariable Cox regression, a high monocyte-to-lymphocyte ratio (MLR ≥0.37), positive surgical margins, and pathological nodal involvement remained independently associated with worse DFS after confounder adjustment (HR 9.73, 10.78, and 17.71, respectively). Conclusions: Elevated MLR, histological node metastases, and positive surgical margins independently predict recurrence in MTC after curative treatment. Preoperative MLR may represent a simple, inexpensive, and reproducible biomarker to improve preoperative risk stratification and personalize surgical and follow-up strategies: patients with MLR ≥0.37 may benefit from more aggressive management and/or closer follow-up.

Purpose To underline discrepancies between the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) classifications in oral cavity cancer. Methods Comparison between the UICC and AJCC TNM classifications of oral cavity cancer in their 8th editions and following versions. Results The most important update was the introduction of the depth of infiltration (DOI), which reflects the proximity of the tumor to the underlying lymphovascular tissues and was associated to the presence of nodal metastases. Since the first publication of the 8th edition of the AJCC Cancer Staging Manual on March 30, 2017, two further versions have been published, while the UICC TNM classification was left unchanged until a document containing modifications to the 8th edition of the UICC TNM Classification of Malignant Tumours was published online on October 6, 2020. Conclusion Different versions of the TNM classification can be confounding for the scientific community. Citing the 8th edition of the UICC TNM Classification of Malignant Tumours or the AJCC Cancer Staging Manual without specifying the precise version used for classification may be insufficient. Clinicians and researchers are invited to always refer to the latest update of each classification.

Chronic rhinosinusitis (CRS) and nasal septum deviation (SD) are two widely diffused clinical conditions in otorhinolaryngology clinical practice. Albeit nasal symptoms are the most commonly referred by patients affected by both conditions, recent evidence has explored the impairment of nasal function beyond its local implication. Indeed, the prevalence of psychiatric disorders, specifically anxiety and depression, was found higher in patients suffering from SD or CRS than in the general population. The aim of this study was to evaluate the psychiatric burden of these conditions in terms of anxiety and depression and to assess its relationship with clinical phenotype and age. Monocentric cross-sectional observational study. Consecutive patients affected by CRS with or without nasal polyps or by SD were considered eligible. At referral, each patient underwent nasal endoscopy for clinical diagnosis and had to fill in the Hospital Anxiety and Depression Scale (HADS), the Sinonasal Outcome Test-22 (SNOT-22), and the Visual Analogue Scale (VAS) for global nasal symptoms. The population was grouped according to disease and age. One hundred fifty patients were enrolled. We observed a statistically significant difference in mean HADS score between patients affected by CRS with nasal polyps and those suffering from CRS without nasal polyps or SD both in the overall population and by age groups. Nevertheless, there was no significant difference in the HADS score between younger patients affected by CRS and SD. The mean HADS score was significantly higher in younger patients affected by SD compared to older. Furthermore, we observed an inverse correlation between age and HADS score in each disease group, statistically significant for SD. On the contrary, in the overall population, HADS score and patient-related outcomes (PROs) were directly correlated.  Conclusions: In the era of personalized medicine, our work remarks on the critical impact of anxiety and depression on the quality of life (QoL) of patients affected by sinonasal conditions. According to our results, age affects patient-reported outcomes (PROs) and should, therefore, be enhanced in the therapeutic decision process.

Background Although there are reports of otolaryngological symptoms and manifestations of CoronaVirus Disease 19 (COVID-19), there have been no documented cases of sudden neck swelling with rash in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection described in literature. Case presentation We report a case of a sudden neck swelling and rash likely due to late SARS-CoV-2 in a 64-year-old woman. The patient reported COVID-19 symptoms over the previous three weeks. Computed Tomography (CT) revealed a diffuse soft-tissue swelling and edema of subcutaneous tissue, hypodermis, and muscular and deep fascial planes. All the differential diagnoses were ruled out. Both the anamnestic history of the patient’s husband who had died of COVID-19 with and the collateral findings of pneumonia and esophageal wall edema suggested the association with COVID-19. This was confirmed by nasopharyngeal swab polymerase chain reaction. The patient was treated with lopinavir/ritonavir, hydroxychloroquine and piperacillin/tazobactam for 7 days. The neck swelling resolved in less than 24 h, while the erythema was still present up to two days later. The patient was discharged after seven days in good clinical condition and with a negative swab. Conclusion Sudden neck swelling with rash may be a coincidental presentation, but, in the pandemic context, it is most likely a direct or indirect complication of COVID-19.

BackgroundThe value of Prostate Specific Membrane Antigen (PSMA) in thyroid carcinoma (TC) is still unknown. We aimed to test the potential complementary role of PSMA expression and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake on PET/CT as biomarkers for TC outcome prediction.Materials and methodsFrom a retrospective cohort of TC patients we selected those fulfilling the following inclusion/exclusion criteria: thyroidectomy in our Institution, available primary tumor tissue PSMA immunostaining, [18F]FDG PET/CT and follow-up data. PSMA staining was visually assessed. PET/CT was considered positive in case of [18F]FDG uptake higher than the background at the site of TC confirmed by cyto-/histology, and/or follow-up. Disease recurrence, radioiodine refractoriness (RAI-R) and status at last follow-up (LFU) were used as outcome endpoints.ResultsWe included 23 subjects. Disease recurrence occurred in 18 patients (median time 11 months, range 1–40); among these 12/18 developed RAI-R (median time 28 months, range 2–221), and 13/18 had evidence of disease at LFU. PSMA expression was negative in 6/23 cases. PET/CT was negative in 11/23 patients (7/11 experienced recurrence). PET/CT was positive in 9/12 patients showing RAI-R and 10/13 cases with evidence of disease at LFU. All patients with positive PET/CT had a positive PSMA immunostaining. Six out of 11 patients with negative PET/CT were positive at immunostaining, showing lower PSMA expression (median score of 30%, range 0–80%) than patients with positive PET/CT. The TC samples without PSMA expression belonged to patients who resulted negative also at PET/CT (3 experienced recurrence, 2 were RAI-R, and 1 had disease at LFU). Four out of 11 patients who resulted negative at PET/CT exhibited very high PSMA expression (≥ 70%) and although 3 of them experienced recurrence, none resulted RAI-R, and only 1 had persistent disease at LFU.ConclusionsPrimary tumor PSMA expression and [18F]FDG uptake seem to play a complementary prognostic role in TC. The majority of patients who expressed PSMA recurred. In the intermediate ATA risk class, patients with negative PSMA immunostaining recurred less than patients expressing PSMA. Additionally, although patients with a negative [18F]FDG PET/CT had a favourable long-term outcome, PSMA assessment might be useful to timely identify subjects at higher risk of recurrence.

Introduction: International guidelines include transoral robotic surgery (TORS) as an option for selected oropharyngeal squamous cell carcinomas (OPSCCs). In the perspective of treatment de-intensification, many surgeons have started recommending and performing TORS preferentially in p16- positive OPSCC in order to reduce the long-term morbidity related to chemoradiotherapy. The aim of the present review is to analyze the current evidence supporting the above-cited strategy. Materials and Methods: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Twenty-two studies were included in this review, with a total of 3992 patients treated with primary TORS. The majority of patients were classified as HPV+ (n = 3655, 91.6%), and 8.2% (n = 327) as HPV−. The HPV status was unknown in only 10 (0.3%) patients. In particular, only five of the included studies compared survival outcomes of HPV−positive patients with HPV−negative ones treated with primary TORS, and only two of these found a significant improvement in survival in the HPV−driven cohort. Discussion: The current literature does not clarify whether HPV+ OPSCCs treated with TORS, alone or with adjuvant treatments, are associated with a better oncologic and/or functional outcome compared to those treated with radio- or chemoradiotherapy. However, TORS alone obtained good oncological outcomes in a high percentage of cases in the reviewed series. Recent data, on the other hand, suggest that TORS could represent a promising strategy for intensifying treatments in HPV− OPSCC.

(1) Background: The assessment of resection margins during surgery of oral cavity squamous cell cancer (OCSCC) dramatically impacts the prognosis of the patient as well as the need for adjuvant treatment in the future. Currently there is an unmet need to improve OCSCC surgical margins which appear to be involved in around 45% cases. Intraoperative imaging techniques, magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS), have emerged as promising tools in guiding surgical resection, although the number of studies available on this subject is still low. The aim of this diagnostic test accuracy (DTA) review is to investigate the accuracy of intraoperative imaging in the assessment of OCSCC margins. (2) Methods: By using the Cochrane-supported platform Review Manager version 5.4, a systematic search was performed on the online databases MEDLINE-EMBASE-CENTRAL using the keywords “oral cavity cancer, squamous cell carcinoma, tongue cancer, surgical margins, magnetic resonance imaging, intraoperative, intra-oral ultrasound”. (3) Results: Ten papers were identified for full-text analysis. The negative predictive value (cutoff < 5 mm) for ioUS ranged from 0.55 to 0.91, that of MRI ranged from 0.5 to 0.91; accuracy analysis performed on four selected studies showed a sensitivity ranging from 0.07 to 0.75 and specificity ranging from 0.81 to 1. Image guidance allowed for a mean improvement in free margin resection of 35%. (4) Conclusions: IoUS shows comparable accuracy to that of ex vivo MRI for the assessment of close and involved surgical margins, and should be preferred as the more affordable and reproducible technique. Both techniques showed higher diagnostic yield if applied to early OCSCC (T1–T2 stages), and when histology is favorable.