Non-Mucosa Sparing (Reboot) Surgery as a Possible Rescue Therapy in Patients Locally Unresponsive to Biologics.

Objective: Evaluation of effectiveness of non-mucosa-sparing (eg, reboot) surgery in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), poorly responders to mAb therapy, who failed repeated comprehensive endoscopic surgeries. Methods: Retrospective observational study. Patients who were under mAb for a comorbid condition but still had no control over their CRSwNP were included. Data collected were preoperative tissue eosinophilia, nasal polyp score (NPS), 22-item sinonasal outcome test (SNOT-22), visual analog scale (VAS) for nasal symptoms, Lund-Kennedy score for nasal crusts (LK-c) and synechiae (LK-s), and Lund-Mackay score (LMS). The same data were also collected postoperatively (at 12 months), besides LMS, and compared. Results: Overall, 20 patients were included. Pre-reboot scores were: NPS = 4.95 ± 1.70; SNOT-22 = 63.90 ± 19.15; VAS-global = 7.06 ± 1.50; LM = 19.0 ± 4.01; LK-c = 1.10 ± 0.64; and LK-s = 1.30 ± 0.73. Tissue biopsies revealed a high density of eosinophils in all cases, ≥10/HPF (range 10-60). Mean postoperative outcomes were: NPS = 0; SNOT-22 = 17.90 ± 6.80; VAS-global = 1.91 ± 1.17; LK-c = 1.45 ± 0.51; and LK-s = 1.50 ± 0.61. The difference of mean pre- and postoperative scores was significant for both NPS, SNOT-22 and VAS-global (P < .001). No differences were observed for LK-c and LK-s (P > .05). Nasal specimens showed markedly reduced tissue eosinophils (100% of cases). Conclusion: Reboot sinus surgery might be an effective solution for recalcitrant CRSwNP patients unresponsive to mAbs and multiple sinus surgeries.

Development of machine learning models to predict papillary carcinoma in thyroid nodules: The role of immunological, radiologic, cytologic and radiomic features.

OBJECTIVE: Approximately 30 % of thyroid nodules yield an indeterminate diagnosis through conventional diagnostic strategies. The aim of this study was to develop machine learning (ML) models capable of identifying papillary thyroid carcinomas using preoperative variables. METHODS: Patients with thyroid nodules undergoing thyroid surgery were enrolled in a retrospective monocentric study. Six 2-class supervised ML models were developed to predict papillary thyroid carcinoma, by sequentially incorporating clinical-immunological, ultrasonographic, cytological, and radiomic variables. RESULTS: Out of 186 patients, 92 nodules (49.5 %) were papillary thyroid carcinomas in the histological report. The Area Under the Curve (AUC) ranged from 0.41 to 0.61 using only clinical-immunological variables. All ML models exhibited an increased performance when ultrasound variables were included (AUC: 0.95-0.97). The addition of cytological (AUC: 0.86-0.97) and radiomic (AUC: 0.88-0.97) variables did not further improve ML models' performance. CONCLUSION: ML algorithms demonstrated low accuracy when trained with clinical-immunological data. However, the inclusion of radiological data significantly improved the models' performance, while cytopathological and radiomics data did not further improve the accuracy. LEVEL OF EVIDENCE: Level 4.

Endoscopic endonasal dacryocystorhinostomy: impact of long-standing disease on surgical outcomes.

PURPOSE: To assess whether the duration of disease may influence the surgical success of Endonasal Endoscopic DCR (EE-DCR) in patients affected by nasolacrimal duct obstruction (NLDO). METHODS: Single-center observational retrospective analysis on EE-DCR via posterior trans-ethmoidal approach. Consecutive patients were enrolled in 2021-2024 and evaluated with proper questionnaires; resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). Also, patients were asked to complete the Hospital Anxiety and Depression Scale (HADS) at each timepoint. The sample was divided based on the duration of disease (group A: ≤ 24 months, group B: > 24 months). RESULTS: Ninety-one patients were included. At baseline no differences were observed between the two groups. At both timepoints, Munk score was significantly lower in Group A compared to Group B, while a difference in dacryocystitis rate was observed only at T2. Anxiety scores differed significantly at T2, although no differences were observed for depression. At paired analysis, all groups improved significantly at T1 compared to baseline, whereas no further improvement was observed between T2 and T1. A significantly higher improvement was observed in group A for the Munk and HADS-A scores over timepoints, whereas there was no significance for dacryocystitis rate and HADS-D. Also, group A showed a higher complete success rate compared to group B (p = 0.041). Finally, linear regression confirmed a positive relationship between Munk and anxiety scores and the duration of disease at T2. CONCLUSIONS: Our findings showed that long-lasting NLDO symptoms may be associated with worse EE-DCR surgical outcomes.

Camera-based near-infrared autofluorescence versus visual identification in total thyroidectomy for parathyroid function preservation: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Hypocalcemia is the most common postoperative complication of total thyroidectomy. Near-infrared autofluorescence (NIRAF) technology is a surgical adjunct that has been increasingly utilized with the aim of preventing postoperative hypocalcemia, but its clinical benefits have not yet been firmly established. The aim of this study was to assess the clinical benefit of utilizing NIRAF technology in patients undergoing total thyroidectomy. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed according to PRISMA guidelines. RESULTS: Seven randomized clinical trials with 1437 patients (318 males, 22.13%) undergoing total thyroidectomy were included for analysis. Risk of postoperative hypocalcemia was reduced in the NIRAF arm (RR, 0.65; 95%CI, 0.50-0.84). Use of NIRAF was also associated with a reduction in the risk of permanent parathyroid dysfunction (RR, 0.46; 95%CI, 0.22-0.95) and inadvertent parathyroid gland resection (RR, 0.40; 95%CI, 0.26-0.60). CONCLUSIONS: We present a systematic review and meta-analysis of randomized clinical trials examining the impact of NIRAF technology on preservation of parathyroid function. Our results suggest that use of camera-based NIRAF technology reduces the risk of postoperative hypocalcemia, permanent parathyroid dysfunction, and inadvertent parathyroid gland resection.

Computer Vision Foundation Models in Endoscopy: Proof of Concept in Oropharyngeal Cancer.

OBJECTIVES: To evaluate the performance of vision transformer-derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging. METHODS: Computational study using endoscopic frames with a focus on the application of a self-supervised vision transformer model (DINOv2) for tissue classification. High-definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80-20 train-validation split. RESULTS: From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1-score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96. CONCLUSION: The use of large vision model-derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:4535-4541, 2024.

Psychiatric Burden in Chronic Sinonasal Diseases: A Single-Center Cross-Sectional Observational Study.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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.

The Use of Artificial Intelligence in Head and Neck Cancers: A Multidisciplinary Survey.

Artificial intelligence (AI) approaches have been introduced in various disciplines but remain rather unused in head and neck (H&N) cancers. This survey aimed to infer the current applications of and attitudes toward AI in the multidisciplinary care of H&N cancers. From November 2020 to June 2022, a web-based questionnaire examining the relationship between AI usage and professionals' demographics and attitudes was delivered to different professionals involved in H&N cancers through social media and mailing lists. A total of 139 professionals completed the questionnaire. Only 49.7% of the respondents reported having experience with AI. The most frequent AI users were radiologists (66.2%). Significant predictors of AI use were primary specialty (V = 0.455; p < 0.001), academic qualification and age. AI's potential was seen in the improvement of diagnostic accuracy (72%), surgical planning (64.7%), treatment selection (57.6%), risk assessment (50.4%) and the prediction of complications (45.3%). Among participants, 42.7% had significant concerns over AI use, with the most frequent being the 'loss of control' (27.6%) and 'diagnostic errors' (57.0%). This survey reveals limited engagement with AI in multidisciplinary H&N cancer care, highlighting the need for broader implementation and further studies to explore its acceptance and benefits.

Outcomes of Endoscopic Endonasal Dacryocystorhinostomy in Glaucoma Patients.

BACKGROUND: Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. We aimed to assess whether these effects may impair the effectiveness of endoscopic endonasal dacryocystorhinostomy (EE-DCR). METHODS: This is a single-center observational retrospective study on EE-DCR via a posterior approach. Resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score). RESULTS: Twenty patients (32 sides) were enrolled. Preoperatively, 93.75% (n = 30/32) presented severe (Munk 3-4) epiphora and 68.75% (n = 22/32) recurrent dacryocystitis. At T1, 50.0% (n = 16/32) were referred with residual epiphora (Munk ≥ 1) and 18.75% (n = 6/32) dacryocystitis. At T2, 31.25% (n = 10/32) still complained of epiphora (Munk ≥ 1) and 6.25% (n = 2/32) dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted in statistical significance (p < 0.05). At T2, 22 (68.75%) complete, 8 (25.0%) anatomical successes and 2 (6.25%) surgical failures were observed. CONCLUSIONS: Despite the chronic uptake of anti-glaucoma eye drops, EE-DCR guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis.

Management of nasal vestibule carcinomas: recommendations by the Oncological Committee of the Italian Society of Otorhinolaryngology - Head and Neck Surgery.

Objective: Squamous cell carcinoma of the nasal vestibule (NV SCC) is a head and neck malignancy for which there is no established consensus on most aspects of clinical management. The purpose of this document is to give updated recommendations that incorporate recent evidence on its clinical characteristics and the high efficacy of brachytherapy as primary treatment modality. Methods: A working group consisting of the members of the Scientific Committee for Oncology and Reconstructive Surgery of the Italian Society of Otorhinolaryngology Head and Neck Surgery and radiation oncologists expert in brachytherapy was formed to achieve a consensus. Results: Consensus was reached on a set of recommendations, proposing a refined anatomical definition of the nasal vestibule, a novel T staging system of the NV SCC, and brachytherapy as standard of care, with a new method for catheter implantation. Conclusions: The Committee emphasises the critical role of an accurate classification in clinical practice and encourages further research to validate the novel staging system and further improve treatment strategies. Where appropriate, it is recommended that patients be referred to centres with specific experience in brachytherapy for NV SCC.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

PURPOSE: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach). METHODS: A prospective observational study, recruiting 40 patients undergoing surgery for pituitary adenoma, 20 via Endonasal approach and 20 via Trans-septal approach at our institution. Surveys with Sinonasal Outcome Test-22 (SNOT-22), Chronic Sinusitis Survey (CSS), and Short Form Health Survey 36 version 2 (SF-36v2) were obtained to collect QoL data pre- and postoperatively. RESULTS: All the 40 patients completed the questionnaires. At 6 months postoperatively, the SNOT-22 and CSS score shows significant improvements both in Endonasal approach (p = 0.01) and in Trans-septal approach (p = 0.02). No significant difference in sinonasal morbidity is observed between the two groups for SNOT-22 (p = 0.13) and CSS scores, except for sinus headache (p = 0.49), with a better score in Endonasal approach. The mean SF-36v2 scores remain the same in pre- and post-operative periods, but an improvement in time is seen in general health (p = 0.027), and general health compared to one year ago (p < 0.001). CONCLUSIONS: Endoscopic transsphenoidal surgery has negligible morbidity and does not negatively affect the nasal function in the long term. Endonasal approach and Trans-septal approach are comparable in terms of morbidity outcomes and general QoL, leaving the choice of the approach to the surgeon preference.

Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Radiological Versus Clinical 1-Year Outcomes of Dupilumab in Refractory CRSwNP: A Real-Life Study.

OBJECTIVE: To provide real-life evidence on long-term radiological changes in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab, and to assess possible differences between radiological and clinical results in terms of endoscopic findings and Patient-Reported-Outcomes (PROs). METHODS: Consecutive patients treated with dupilumab for recalcitrant CRSwNP were required to undergo CT scan at baseline (T0) and after 12 (T1) since first administration. A group of patients also performed CT scan at 52 weeks (T2) to assess long-term outcomes. At each timepoint, patients underwent nasal endoscopy, assessment of Nasal-Polyp-Score (NPS), Lund-Kennedy-Score (LKS), and had to fill in the 22-item Sinonasal-Outcome-Test (SNOT-22) and Visual-Analogue-Scales (VAS) for sinonasal symptoms. RESULTS: In fifty-three included patients, from T0 to T1 we detected a significant reduction in mean Lund-Mackay score (LM), PROs (SNOT-22, VAS) and endoscopic (NPS, LKS) scores (p < 0.05). In the subset of patients that reached T2 (n = 30), compared to T1, we observed a further significant decrease in mean LM, SNOT-22, VAS, and NPS scores, but not in LKS (p = 0.420). At T1, the highest improvement was observed in PROs (SNOT-22: 56.26%), and polyp size (NPS: 49.83%). Conversely, between T1 and T2, sinus opacification was shown to be the most improved outcome (LM: 36.86%). CONCLUSIONS: Our experience showed that poorly controlled CRSwNP patients treated with dupilumab experienced significant improvement in radiologic, endoscopic and clinical disease severity. While in the initial 3 months, PROs garnered attention for showing earlier effectiveness, radiological outcomes revealed sustained and gradual efficacy in a longer term. LEVEL OF EVIDENCE: Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 134:2626-2633, 2024.

Squamous Cell Carcinoma of the Nasal Vestibule: A Multi-Centric Observational Cohort Study.

OBJECTIVES: Squamous cell carcinoma of the nasal vestibule (NV-SCC) is a rare but challenging entity, due to the complex anatomy of the region. Consensus on the best treatment strategy is still lacking, as well as a dedicated staging system. Our aim was to analyze oncological outcomes of surgically treated patients and to investigate possible prognostic factors. METHODS: We performed a retrospective multi-centric observational study including six Academic Hospitals over a 10-year period, including only patients who underwent upfront surgery for primary NV-SCC. Patients were staged according to all currently available staging systems. The Kaplan-Meier method was used to compute overall, disease-free, and disease-specific survival. Logistic regression models were used to correlate between survival outcomes and clinical and pathological variables. RESULTS: Seventy-one patients with a median follow-up of 38 months were included in the study. Partial and total rhinectomy were the most commonly performed procedures, respectively, in 49.3% and 25.4% of cases. Neck dissection was performed on 31% of patients, and 45.1% of them underwent adjuvant radiotherapy. Three years overall, disease-specific and disease-free survival were, respectively, 86.5%, 90.3%, and 74.2%. None of the currently available staging systems were able to effectively stratify survival outcomes. Factors predicting lower overall survival on multivariate analysis were age (p = 0.021) and perineural invasion (p = 0.059), whereas disease-free survival was negatively affected by age (p = 0.033) and lymphovascular invasion (p = 0.019). CONCLUSION: Currently available staging systems cannot stratify prognosis for patients who underwent surgery for NV-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2634-2645, 2024.

Preoperative systemic inflammatory markers as prognostic factors in differentiated thyroid cancer: a systematic review and meta-analysis.

BACKGROUND: Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain. OBJECTIVE: This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC. METHODS: Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model. RESULTS: A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR. CONCLUSIONS: Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Trans oral robotic surgery for oropharyngeal cancer: A multi institutional experience.

OBJECTIVES: Trans Oral Robotic Surgery (TORS) has proved to be a safe and feasible treatment for oropharyngeal squamous cell carcinoma (OPSCC). The aim of this study is to analyse oncological outcomes of OPSCC patients treated with TORS. MATERIALS AND METHODS: This study involved 139 patients with OPSCC, treated with TORS between 2008 and 2020. Clinicopathological characteristics, treatment details and oncological outcomes were evaluated retrospectively. RESULTS: The management strategies included TORS alone in 42.5%, TORS-RT in 25.2% and TORS-CRT in 30.9%. The ENE was noted in 28.8% of neck dissections. In 19 patients clinically classified as unknown primaries, the primary was found in 73.7%. Rates of local, regional relapses and distant metastasis were 8.6%, 7.2%, and 6.5%, respectively. The 5 year- Overall Survival and Disease Free Survival were 69.6% and 71.3%, respectively. CONCLUSION: TORS fits well in the modern management of OPSCC. Although definitive CRT remains a milestone, TORS is proving to be a valid and safe treatment option. The choice of the therapeutic strategy requires evaluation by a multidisciplinary team.

Image-Guided Intraoperative Assessment of Surgical Margins in Oral Cavity Squamous Cell Cancer: A Diagnostic Test Accuracy Review.

(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.

The complementary role of PSMA expression and [18F]FDG PET/CT in predicting thyroid cancer outcome: from black and white to shades of gray, in the era of precision oncology.

BACKGROUND: The 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 METHODS: From 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. RESULTS: We 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. CONCLUSIONS: Primary 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.

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.

PURPOSE: Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. METHODS: This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA-LUT alone; (3) twice daily um-PEA-LUT alone; or (4) combination of once daily um-PEA-LUT with olfactory training. Olfactory testing (Sniffin' Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T0, T1, T2 and T3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. RESULTS: All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA-LUT alone, and 41.6% receiving once daily um-PEA-LUT alone (p < 0.00001). Patients receiving treatment with um-PEA-LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo (p < 0.0001.) CONCLUSIONS: Olfactory training plus once daily um-PEA-LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. TRIAL REGISTRATION: 20112020PGFN on clinicaltrials.gov. LEVEL OF EVIDENCE: 1b (Individual Randomized Clinical Trial).