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.

Vocal Cord Monitoring by Flexible Fiberoptic Laryngoscopy During Thyroid Radiofrequency Ablation.

Introduction: Thermal injury to recurrent laryngeal nerve (RLN) during radiofrequency ablation (RFA) can produce temporary or permanent vocal cord paralysis.1 Hydrodissection with cold 5% glucose of "danger triangle" protects RLN during RFA.2 When RFA is performed under local anesthesia, RLN function is monitored by patients producing vocal sounds.3 Large lesions requiring longer RFAs warrant general sedation where voice cannot be assessed, therefore, an additional technique for RLN protection is advisable. Observation of passive symmetrical vocal cord movements during breathing by laryngeal ultrasonography is useful in assessing vocal cord function4; however, flexible-fiberoptic fibrolaringoscopy (FFL) is gold standard for assessing vocal cord movements,5 anticipating potential RLN damage. We report FFL monitoring during RFA under general sedation on a large thyroid nodule. FFL during RFA may detect RLN irritation and dysfunction if asymmetry in passive vocal cord movements is noted. Should asymmetry appear, RFA operator stops delivering energy and repositions electrode needle. Materials and Methods: Thyroid function tests, blood glucose, creatinine, transaminase, International-Normalized-Ratio, and electrocardiogram were performed. Operating room (OR) layout created sufficient space for ear-nose-throat (ENT) and RFA operators. An examination with a fiberscope camera demonstrated normal vocal cord adduction during phonation and abduction during breathing. The procedure was assisted by an anesthetist administering fentanyl 50 mcg, midazolam 1.5 to 5.0 mg, and propofol infusion 2 mg/(kg·h). General sedation was conducted so that reflexes were attenuated but still observable. Incorporating in OR by an anesthetist who performs general sedation reduces side effects and complications.6 Ultrasonography showed a 34-mL right lobe nodule abutting on the RLN area. After sedation with propofol, the ENT specialist inserted an endoscope until the glottic plane. During calm breathing, vocal cords moved symmetrically. After obtaining anterior nodule hydrodissection from strap and sternocleidomastoid muscles with 10 mL of 2% lidocaine, posterior hydrodissection was achieved by ultrasound-guided administration of 30 mL of 5% cold glucose. Anterior and posterior hydrodissections merged, separating nodule from neck structures. The radiofrequency electrode needle was then inserted into the nodule, initially positioned in inferior nodule portion adjacent to danger triangle previously isolated by hydrodissection. Initial power was 30 watts. Moving-shot technique was used. Results: FFL was performed throughout thyroid RFA. Symmetric vocal cord movements during breathing demonstrated no RLN irritation. FFL monitoring allowed observation of natural reflexive phenomena, including swallowing. Complete nodule ablation was achieved. FFL performed post-RFA confirmed normal vocal cord motility. Conclusions: We report the first-time use of FFL for vocal cord monitoring during RFA. FFL was easily performed by the ENT specialist and well tolerated by the patient. Avoiding danger triangle and precise RFA needle positioning is key in preventing RLN injury. Benign nodules regrow if total ablation is not achieved7 and some authors propose additional procedures to complete ablation8 that obviously incurs costs. Total RFA nodule ablation-assisted FFL monitoring eliminates the need for repetitive RFAs, thus reducing overall treatment costs. Finally, FFL monitoring does not prolong procedure, as it is performed simultaneously with RFA. FFL is a valid technique when used in conjunction with hydrodissection to further prevent RLN thermal injury during RFA, especially indicated for large thyroid nodule ablation and professional voice users. Patient Consent and Permission: The patient provided written consent for FFL monitoring and permission to use his portrayals and ultrasonographic images during RFA. The study was completed in accordance with the Declaration of Helsinki as revised in 2013. Adherence to institutional review board protocols was granted. Disclaimer: Representation of any instrumentation within the video does not indicate any endorsement of the product and/or company by the publisher, the American Thyroid Association, or the authors. No competing financial interests exist. Runtime of video: 9 mins 39 secs.

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).

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

Long-standing gustatory and olfactory dysfunction in COVID-19 patients: a prospective study.

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.

An approach to evaluate the quality of radiological reports in Head and Neck cancer loco-regional staging: experience of two Academic Hospitals.

OBJECTIVES: To evaluate the quality of the reports of loco-regional staging computed tomography (CT) or magnetic resonance imaging (MRI) in head and neck (H&N) cancer. METHODS: Consecutive reports of staging CT and MRI of all H&N cancer cases from 2018 to 2020 were collected. We created lists of quality indicators for tumor (T) for each district and for node (N). We marked these as 0 or 1 in the report calculating a report score (RS) and a maximum sum (MS) of each list. Two radiologists and two otolaryngologists in consensus classified reports as low quality (LQ) if the RS fell in the percentage range 0-59% of MS and as high quality (HQ) if it fell in the range 60-100%, annotating technique and district. We evaluated the distribution of reports in these categories. RESULTS: Two hundred thirty-seven reports (97 CT and 140 MRI) of 95 oral cavity, 52 laryngeal, 47 oropharyngeal, 19 hypo-pharyngeal, 14 parotid, and 10 nasopharyngeal cancers were included. Sixty-six percent of all the reports were LQ for T, 66% out of all the MRI reports, and 65% out of all CT reports were LQ. Eight-five percent of reports were HQ for N, 85% out of all the MRI reports, and 82% out of all CT reports were HQ. Reports of oral cavity, oro-nasopharynx, and parotid were LQ, respectively, in 76%, 73%, 100% and 92 out of cases. CONCLUSION: Reports of staging CT/MRI in H&N cancer were LQ for T description and HQ for N description.

Discrepancies between UICC and AJCC TNM classifications for oral cavity tumors in the 8th editions and following versions.

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.

Frozen Section Analysis and Real-Time Magnetic Resonance Imaging of Surgical Specimen Oriented on 3D Printed Tongue Model to Assess Surgical Margins in Oral Tongue Carcinoma: Preliminary Results.

BACKGROUND: A surgical margin is the apparently healthy tissue around a tumor which has been removed. In oral cavity carcinoma, a negative margin is considered ≥ 5 mm, a close margin between 1 and 5 mm, and a positive margin ≤ 1 mm. Currently, the intraoperative surgical margin status is based on the visual inspection and tissue palpation by the surgeon and intraoperative histopathological assessment of the resection margins by frozen section analysis (FSA). FSA technique is limited and susceptible to sampling errors. Definitive information on the deep resection margins requires postoperative histopathological analysis. METHODS: We described a novel approach for the assessment of intraoperative surgical margins by examining a surgical specimen oriented through a 3D-printed specific patient tongue with real-time Magnetic Resonance Imaging (MRI). We reported the preliminary results of a case series of 10 patients, prospectively enrolled, with oral tongue carcinoma who underwent surgery between February 2020 and April 2021. Two radiologists with 5 and 10 years of experience, respectively, in Head and Neck radiology in consensus evaluated specimen MRI and measured the distance between the tumor and the specimen surface. We performed intraoperative bedside FSA. To compare the performance of bedside FSA and MRI in predicting definitive margin status we computed the weighted sensitivity (SE), specificity (SP), accuracy (ACC), area under the ROC curve (AUC), F1-score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). To express the concordance between FSA and ex-vivo MRI we reported the jaccard index. RESULTS: Intraoperative bedside FSA showed SE of 90%, SP of 100%, F1 of 95%, ACC of 0.9%, PPV of 100%, NPV (not a number), and jaccard of 90%, and ex-vivo MRI showed SE of 100%, SP of 100%, F1 of 100%, ACC of 100%, PPV of 100%, NPV of 100%, and jaccard of 100%. These results needed to be validated in a larger sample size of 21- 44 patients. CONCLUSION: The presented method allows a more accurate evaluation of surgical margin status, and the first clinical experiences underline the high potential of integrating FSA with ex-vivo MRI of the fresh surgical specimen.

Preoperative predictors of difficult oropharyngeal exposure for transoral robotic surgery: The Pharyngoscore.

BACKGROUND: Insufficient exposure may require termination of procedure in transoral robotic surgery (TORS). The aim of study was to develop a "Pharyngoscore" to quantify the risk of difficult oropharyngeal exposure (DOE) before TORS. METHODS: Three-hundred six patients undergoing any surgical procedure at one Academic Hospital were prospectively enrolled. Oropharynx was exposed with Feyh-Kastenbauer retractor. Exposure was evaluated by direct and endoscopic visualization of the four oropharyngeal subsites. Preoperative clinical/anthropometric parameters were studied in good oropharyngeal exposure and DOE groups. Logistic regression was performed to explore association between clinical/anthropometric parameters and DOE. Statistically significant parameters at multivariate analysis were incorporated into a nomogram. RESULTS: Sixty-five (21.2%) subjects were characterized by DOE. Variables associated with DOE at univariate analysis were male (p = 0.031), modified Mallampati Class (MMC) ≥ III (p < 0.001), smaller interincisor gap (p < 0.001), and larger neck circumference (p = 0.006). MMC, interincisor gap, and neck circumference were significant at multivariate analysis and were presented with a nomogram for creating the Pharyngoscore. CONCLUSIONS: The Pharyngoscore is a promising tool for calculating DOE probability before TORS.

Prevalence of Taste and Smell Dysfunction in Coronavirus Disease 2019.

Importance: Early diagnosis of coronavirus disease 2019 (COVID-19) may help control the diffusion of the disease into the population. Objective: To investigate the presence of sinonasal manifestations at the onset of COVID-19 to achieve an earlier diagnosis. Design, Setting, and Participants: This retrospective telephone survey study investigated patients diagnosed with COVID-19 from March 5 to March 23, 2020, who were hospitalized or discharged from a single referral center. Patients who were unable to answer (intubated, receiving noninvasive ventilation, or deceased) or unreachable by telephone were excluded. Of 359 consecutive patients, 204 fulfilled the inclusion criteria; 76 were unable to answer, 76 were unreachable by telephone, and 3 refused. Exposures: Sinonasal manifestations reported before COVID-19 diagnosis were studied with a validated questionnaire: Italian Sino-Nasal Outcome Test 22 (I-SNOT-22). If reduction of taste and/or smell was documented by item 5 of the I-SNOT-22, further inquiries were made to score them separately on a scale from 0 to 5, with 0 indicating no problem and 5 indicating problem as bad as it can be. Main Outcomes and Measures: The prevalence of sinonasal manifestations preceding COVID-19 diagnosis. Results: Among the 204 patients enrolled (110 [53.9%] male; mean [SD] age, 52.6 [14.4] years), the median I-SNOT-22 total score was 21 (range, 0-73). I-SNOT-22 identified 116 patients (56.9%) with reduction of taste and/or smell, 113 (55.4%) with taste reduction (median score, 5; range, 2-5), and 85 (41.7%) with smell reduction (median score, 5; range, 1-5). Eighty-two patients (40.2%) reported both. Severe reduction of taste was present in 81 patients (39.7%), and severe reduction of smell was present in 72 patients (35.3%). Only 12 patients (14.8%) with severe taste reduction and 12 patients (16.7%) with severe smell reduction reported severe nasal obstruction. Severe reduction of taste and smell was more prevalent in female vs male patients (odds ratios, 3.16 [95% CI, 1.76-5.67] vs 2.58 [95% CI, 1.43-4.65]) and middle-aged vs younger patients (effect sizes, 0.50 [95% CI, 0.21-0.78] vs 0.85 [95% CI, 0.55-1.15]). No significant association was observed between smoking habits and severe reduction of taste (odds ratio, 0.95; 95% CI, 0.53-1.71) and/or smell (odds ratio, 0.65; 95% CI, 0.35-1.21). Conclusions and Relevance: The findings of this telephone survey study suggest that reduction of taste and/or smell may be a frequent and early symptom of COVID-19. Nasal obstruction was not commonly present at the onset of the disease in this study. The general practitioner may play a pivotal role in identifying potential COVID-19 in patients at an early stage if taste and/or smell alterations manifest and in suggesting quarantine before confirmation or exclusion of the diagnosis.

Trans-Oral Robotic Surgery in the Management of a Supraglottic Solitary Fibrous Tumor.

Trans-oral robotic surgery (TORS) has become increasingly widespread for the head and neck surgery procedures. In this paper, the authors describe the first reported TORS in the management of a laryngeal solitary fibrous tumor (SFT). A 77-year-old woman suffered from progressive dysphonia lasting 2 years and occasional dyspnea. A submucosal mass of about 4 cm in diameter involving the left supraglottis and left aryepiglottic fold was detected during the flexible fibre-optic laryngeal examination. Magnetic resonance imaging revealed a solid, well-demarcated mass (36 × 25 mm), hyperintense with nonhomogeneous contrast enhancement in T2-weighted sequences. The lesion was successfully removed en bloc using the daVinci Xi system (Intuitive Surgical, Sunnyvale, CA) equipped with 3 robotic arms (1 3-dimensional endoscopic arm, 1 monopolar cautery, 1 bipolar Maryland forceps). The postoperative course was regular, and the endoscopic examination at 1 month showed normal laryngeal morphology and function. Trans-oral robotic surgery has proved to be a good alternative to conventional trans-oral approaches in the treatment of laryngeal SFT. The lesion was completely removed without intraoperative complications, and postoperative morbidity was minimized. Further comparative studies are recommended to define if TORS could become the gold standard for the surgical treatment of laryngeal SFTs.

"L" shape technique for endoscopic sinus surgery: An alternative method.

BACKGROUND: Several techniques for performing ethmoidectomy have been reported. We describe a safe, effective and efficient technique during functional endoscopic sinus surgery (FESS). We present text, images and videos to illustrate our preferred technique during an antero-posterior ethmoidectomy and to provide a multimedia tool for educational purpose. METHODS: A description of the technique without prospective or retrospective data is reported. A complete ethmoidectomy with an L-shape approach is described step-by-step, using the backbiting circular and miniature cutting forceps, with safe exposure of the lamina papyracea (LP) and skull base. RESULTS: In our hands, the L-shape approach for chronic rhinosinusitis with or without polyposis, performed with punch circular cutting and miniature cutting forceps, allowed for a reliably safe and efficient ethmoidectomy. CONCLUSION: The technique described can be added to the armamentarium of the endoscopic sinus surgeon.

Preliminary clinical experience with the 4 K3-dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction.

BACKGROUND: To demonstrate the use of a 4 K 3-dimensional microvideoscope (VITOM 3D) system for free flap head and neck reconstruction. METHODS: Clinical human study of free flap harvesting and microvascular anastomosis in patients undergoing reconstruction after ablative surgery for head and neck carcinoma. The video shows the harvesting of a chimeric myofascial/fascio-cutaneous anterolateral thigh free flap and microvascular anastomosis using different techniques. RESULTS: The VITOM 3D exoscope system provided sufficient access, reach, and visualization to perform successfully free flap harvesting and microvascular anastomosis. Using the 3D glasses, both surgeons and nurses can have the same visualization throughout the entire procedure. We performed 10 arterial and venous anastomosis without significant complications. CONCLUSIONS: This study demonstrates the technical feasibility of free flap harvesting and microvascular anastomosis using the 4 K3-Dimensional Microvideoscope (VITOM 3D) System.