Importance:Intraoperative neuromonitoring (IONM) may prevent bilateral vocal cord palsy after thyroidectomy by prompting the surgeon to abort planned total thyroidectomy in case of loss of signal from the recurrent laryngeal nerve (RLN) on the first side. The International Nerve Monitoring Study Group recommends stimulation in the sequence V1 (predissection vagus nerve), R1 (predissection RLN), R2 (postdissection RLN), V2 (postdissection vagus nerve). Objectives:To investigate sensitivity of V2 stimulation for identification of postoperative vocal cord palsy vs R2 stimulation only. Design, Setting, and Participants:This retrospective cross-sectional study included patients undergoing thyroidectomy from February 2024 to October 2025, using IONM with stimulation in the sequence of V1, R1, R2, V2. The findings were compared with previous cohort of 1159 nerves at risk (NARs) for which vagal nerve stimulation was performed selectively. The study was performed at an academic tertiary referral center for thyroid surgery. Consecutive patients planned for thyroidectomy were included. Inclusion criteria were thyroidectomy performed using intermittent IONM with postoperative laryngoscopy. Exclusion criteria were preoperative vocal cord palsy, deliberate or inadvertent RLN section, or no postoperative laryngoscopy performed. Exposures:V2 stimulation. Main Outcomes and Measures:The primary outcome measure was vocal mobility on the first postoperative day. The sensitivity, specificity, negative predictive value, and positive predictive value of the 2 strategies were compared. Results:Among 240 patients (mean [SD] age, 50 [15] years; 188 [78.3%] female patients), 43 of 353 NARs (12.2%) had loss of signal (33 [9.3%] persistent). Of these, 9 (27.3%) had V2 loss of signal, with no preceding loss of signal or electrophysiological events on the RLN. Six patients planned for total thyroidectomy had change in operative plan to lobectomy only, including 2 patients with unexpected V2 loss of signal. Impaired vocal mobility was present in 7 of 9 cases with intact R2 and absent V2 response (77.8%). The sensitivity of R2 and V2 stimulation for postoperative vocal cord palsy was 57.9% and 100%, respectively. Among the earlier cohort undergoing selective vagal nerve stimulation, the sensitivity of IONM for impaired vocal cord mobility was 83.3%. Conclusion and Relevance:The findings of this cross-sectional study suggest that IONM without systematic V2 stimulation has inferior sensitivity to systematic V2 stimulation. Systematic V2 stimulation should be considered criterion standard to minimize risk of bilateral vocal cord palsy after total thyroidectomy.

PURPOSE OF REVIEW:Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been recognized as a diagnostic entity since 2017. It has been shown to exhibit indolent behaviour, and lobectomy alone is advocated as the treatment of choice. In this review, the diagnostic challenges including interobserver variation, the role of artificial intelligence, and the latest data on the risk of recurrence or metastasis, is evaluated. RECENT FINDINGS:Diagnosis of NIFTP is reliant on examination of the entire tumour-parenchymal interface. Strict criteria are required in order to establish a diagnosis. Inter-observer variation exists even among experienced thyroid pathologists. Recent studies continue to support the nonaggressive nature of NIFTP lesions. SUMMARY:NIFTP is considered a low risk follicular-cell derived thyroid neoplasm. Adherence to diagnostic criteria is crucial in accurately applying the diagnosis. Further long-term follow up is required in order to establish guidelines on the long term management of these patients.

INTRODUCTION:Regional recurrence (RR) has been reported to occur in 7%-17% of patients with oral squamous cell carcinoma (OSCC) and pathologically negative (pN0) necks. Risk factors for isolated RR, in the absence of simultaneous local recurrence, are poorly defined. Our aim was to study risk factors for isolated RR in early OSCC with clinically and pathologically negative necks. METHODS:Retrospective cohort study of 202 patients with cT1/2N0 OSCC. RESULTS:Among 130 patients undergoing elective neck dissection, 98 were pN0. Five (5.1%) developed isolated RR, and 7 (7.1%) developed any RR. Risk factors for isolated RR were worst pattern of invasion category 5 (WPOI-5) (p = 0.02), and absence of postoperative radiotherapy (PORT) (p = 0.04). Among 170 patients with pN0 or cN0/x necks, risk factors for isolated RR were WPOI-5 and depth of invasion > 10 mm. On multivariate analysis, only WPOI-5 remained significant. CONCLUSION:Isolated RR may occur in over 5% of patients with early OSCC and pathologically negative necks after elective ND. WPOI-5 would appear to be the most important risk factor for isolated RR in pN0 cases. Further work is required to define the role of PORT in patients with WPOI-5. LEVEL OF EVIDENCE: 3:

Correction for 'Mobile multi-configuration clinical translational Raman system for oral cancer application' by Siddra Maryam et al., Analyst, 2023, 148, 1514-1523, https://doi.org/10.1039/D2AN01921C.

OBJECTIVE:Lymph nodal yield (LNY) is increasingly used in oral squamous cell carcinoma (OSCC) research as a prognostic factor and quality metric but remain to be validated across independent OSCC cohorts. STUDY DESIGN:Retrospective cohort study. SETTING:Primary OSCC patients (n = 1080) who underwent a neck dissection, collected from three sites: Brescia, Cork, and Heidelberg. METHODS:The accuracy of LNY in predicting 3- and 5-year mortality was evaluated using the area under the ROC curve (AUC). Binomial regression models, adjusted for LNY and various confounders, were used to cross-validate predictive performance across independent cohorts. A model estimating the population-average treatment effect of LNY was used to estimate the effect of what would have been observed if the OSCC patients had been randomly assigned to have specific ranges of LNYs removed, irrespective of their individual characteristics. Mean LNY was estimated between the three cohorts. RESULTS:ROC curve analysis demonstrated that LNY did not improve prognostic accuracy in predicting 3- and 5-year mortality risks. Cross-validation across independent cohorts showed that adding LNY to the binomial regression models did not improve predictive accuracy. Using the LNY range of 33 to 44 as a reference, the average treatment effect model found no significant difference in the 3-year risk of death across LNY groups (LNY: 2-17, 17-25, 25-33, and 44-119) for pN-positive patients. CONCLUSION:We found no improvement in the prognostic accuracy for mortality when considering LNY in different settings. Substantial inter-center variability and lack of consistent survival benefit challenge the use of LNY as a prognostic or surgical quality metric.

AIMS:Perineural invasion (PNI) is associated with survival in oral cavity squamous cell carcinoma (OCSCC). There is evidence to suggest that PNI location and extent may be of additional significance. The primary aim of this study was to evaluate the prognostic ability of PNI, including location and extent, in early-stage OCSCC. METHODS AND RESULTS:This was a retrospective study, with the main cohort comprising of 129 patients with pT1/T2 pN0/Nx TNM8 OCSCC. Slides were re-reviewed in cases reported as having PNI to classify location as intratumoural (IT) and/or extratumoural (ET) and extent as unifocal (UF) or multifocal (MF). Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. On multivariate analysis, IT PNI was significantly associated with locoregional recurrence-free survival (LRS) [odds ratio = 5.69, 95% confidence interval (CI) = 1.50-21.63, P = 0.01]. Disease-specific survival (DSS) and overall survival (OS) were non-significant. In comparison, ET PNI was predictive of LRS (odds ratio = 20.57, 95% CI = 3.48-121.73, P = 0.001), DSS (odds ratio = 40.47, 95% CI = 5.17-316.96, P = 0.0004) and OS (odds ratio = 11.92, 95% CI = 2.18-65.22, P = 0.004). Multifocal PNI was significant on univariate analysis for all three outcome parameters evaluated, but these findings were not maintained on multivariate assessment. CONCLUSIONS:Extratumoural PNI is strongly predictive of survival outcomes, including OS, in early-stage OCSCC. These findings support the reporting of PNI location as a mandatory data element. The impact of PNI extent requires further study.

BackgroundSelective neck dissection (SND) has traditionally been applied to clinically negative (cN0) necks in mucosal squamous cell carcinoma (SCC). We aimed to examine the oncological safety and patterns of regional recurrence (RR) of SND in clinically positive (cN+) necks.MethodsRetrospective review of prospective cohort of 206 patients with mucosal SCC undergoing neck dissection. RR was classified as occurring within previously dissected levels, within ipsilateral undissected levels, within unusual locations of ipsilateral neck, or contralateral neck.ResultsSeven of seventy-seven (9.1%) cN+ patients undergoing SND developed isolated RR, versus 16.2% after MRND, and 8.7% after SND for cN0 disease. RR was rarely seen within undissected levels of the ipsilateral neck. RR and survival rates were not associated with ND extent (SND vs. MRND) among either cN+ or pN+ patients.ConclusionSND can be safely performed in most patients with cN+ SCC, who do not have gross sternocleidomastoid infiltration or level V metastases.

ImportanceUse of intraoperative neuromonitoring (IONM) during thyroidectomy can nearly eliminate the risk of postoperative bilateral vocal cord palsy (VCP) by indicating staged surgery in cases of loss of signal (LOS) on the first side of planned total thyroidectomy. However, aborting planned total thyroidectomy may lead to persistence of symptoms, delay in adjuvant treatment, and patient inconvenience and distress. There are few data to guide a selective approach to total thyroidectomy in patients with first-side LOS.ObjectiveTo investigate outcomes of immediate bilateral surgery in patients undergoing total thyroidectomy with first-side LOS.Design, Setting, and ParticipantsThis cohort study was a retrospective review of outcomes for patients undergoing thyroidectomy between January 2016 and July 2023 at an academic tertiary referral center for thyroid surgery. Consecutive patients scheduled for total thyroidectomy using IONM were included. Exclusion criteria were preoperative VCP, deliberate sacrifice of recurrent laryngeal nerve (RLN), inadvertent RLN resection, and surgery performed without IONM.ExposuresTotal thyroidectomy performed using IONM.Main Outcome MeasuresVocal mobility on first postoperative day as assessed by flexible laryngoscopy; secondary outcome measures included subjective voice assessment, other postoperative complications, and long-term vocal mobility.ResultsAmong 400 patients undergoing planned total thyroidectomy (mean age, 50.5 years [range, 4-88 years]; 318 female [79.5%]), 51 (12.8%) had first-side LOS, of whom 37 (9.3%) had persistent LOS. Twenty-nine patients (56% of procedures with first-side LOS, including 18 with persistent LOS) proceeded to immediate total thyroidectomy. Postoperatively, 16 patients (55% of patients undergoing total thyroidectomy following first-side LOS, including 14 of 18 with persistent LOS) had impaired vocal mobility. One patient had bilateral VCP that did not require tracheostomy, and 2 had postoperative hypoparathyroidism. Of those whose surgery was aborted after first-side LOS, 8 of 22 (36%) underwent completion thyroidectomy at a later stage. In those undergoing completion thyroidectomy, 2 of 8 (25%) had temporary VCP after the second surgery, 2 (25%) had permanent hypoparathyroidism, and 1 (12.5%) developed inoperable cancer. Postoperative VCP was fully reversible in all but 1 patient.Conclusion and RelevanceAmong patients planned for total thyroidectomy who develop first-side LOS, immediate total thyroidectomy may be considered among those who have pressing reasons for same, and where surgical difficulties might be anticipated in a secondary surgery.

BACKGROUND:The prognostic significance of close margins in oral squamous cell carcinoma (OSCC) is controversial. We wished to investigate the impact of close margins on the risk of local recurrence (LR) in OSCC according to the oral subsite. METHODS:A retrospective cohort study of 342 OSCC patients undergoing primary surgical treatment was conducted. Surgical margins were based on the main specimen and defined as positive (SCC at margins), close (< 5 mm), or clear (≥ 5 mm). RESULTS:Among tongue SCC cases, both positive (hazard ratio 13.48, 95% CI 2.03, 32.91) and close margins (hazard ratio 3.87, 95% CI 1.31, 11.34) were significantly associated with LR. Tongue margins < 4 mm were associated with higher LR. Among non-tongue SCC cases, only positive margins (hazard ratio 4.10, 95% CI 1.19, 14.21) were associated with LR. Close margins were not significant (hazard ratio 1.59, 95% CI 0.46, 5.42). CONCLUSIONS:Close margins appear to have a differential impact on LR in OSCC according to the oral subsite.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units. Immediate extubation is appropriate in many cases where there is a low risk of adverse airway events. Where a prolonged definitive airway is required, elective tracheostomy provides increased airway security postoperatively while delayed extubation may be appropriate in select cases to reduce postoperative morbidity. Local institutional protocols should be developed to care for a tracheostomy once inserted. We provide guidance on decision making surrounding airway management at time of head and neck surgery. All decisions should be agreed between the operating, anesthetic, and critical care teams.

Background: The non-recurrent laryngeal nerve (NRLN) is a rare anatomical variant of the recurrent laryngeal nerve (RLN). It occurs where abnormalities of the aortic arch are present, such as aberrant right subclavian artery, and may be associated with higher risk of iatrogenic injury during thyroid surgery. The presence of NRLN can be detected pre-operatively by ultrasound or volumetric imaging and intra-operatively by direct observation or intra-operative nerve monitoring. To our knowledge, no data has been published on this anomaly in an Irish population. The objective of this study was to ascertain the prevalence of NRLN in a cohort of patients undergoing thyroid surgery in a major head and neck centre in Ireland over an eleven-year period. Methods: This is a retrospective review of 301 patients in a single-centre undergoing thyroid and parathyroid surgery who underwent pre-operative volumetric imaging of the neck between 2008 and 2019. Patients were identified from a prospectively kept operative database of a single surgeon. Patient imaging and reports were reviewed to identify NRLN, calculate its prevalence and calculate the relative risk of nerve injury in patients with this anomaly. Results: A total of 1,127 patients were identified from the database, of whom 301 met the inclusion criteria. Three cases of NRLN were identified (n=3) giving a prevalence of 0.99% in this population. No statistically significant difference in nerve injury rates was found for patients with NRLN versus RLN. Conclusions: The prevalence of NRLN in this population is consistent with international studies and meta-analysis. Although rare, the NRLN represents a clinically important variant of the RLN and one which surgeons operating in the neck should be mindful of. Further data are needed to assess whether NRLN increases relative risk of vocal cord injury.

Anaplastic thyroid cancer (ATC) is considered to be one of the most virulent, treatment-refractory malignancies. Recent molecular insights into the biology of thyroid cancer have transformed ATC management, and BRAF/MEK targeted therapy is now incorporated into guideline-based multidisciplinary care. We report visceral perforation in the setting of an extreme response to such therapy in a patient with ATC. Molecularly targeted therapy afforded a dramatic but life-threatening response to treatment. This report highlights the complexities of care for the patient and treating clinicians.

This study aims to develop a multimodal scheme for diagnosing oral cancer non-invasively in its early stages and to assess the performance of an integrated diagnostic platform comprising of Raman and diffuse reflectance spectroscopy systems.

Background: Thyroglossal duct cysts (TGDCs) are the most common congenital anomaly of thyroid gland development, with a <1% risk of malignancy occurring within them. It's rare for a TGDC to be located in floor of the mouth region or the sublingual space since both these areas are not part of the typical embryological migration route of the thyroid gland. Methods: Herein we report a 42-year-old female patient presenting with a neck mass. Results: A 42-year-old female patient presented with a neck mass, shown on imaging to be located in the sublingual area, with magnetic resonance imaging (MRI) reported findings of a ranula, which on subsequent ultrasound guided fine needle aspiration cytology (FNAC) showed malignant cytology of thyroid origin. Surgical excision and histopathological analysis revealed a TGDC papillary carcinoma within the cyst, a rare diagnosis. Multidisciplinary discussion included review of the imaging, intraoperative and histopathological findings and the case was stratified as low-risk disease with no adjuvant treatment indicated at the time. The patient will be observed closely with active clinical surveillance. Conclusions: There were several important points worth gathering from this case including the need to include TGDC carcinoma in a list of differential diagnoses for a midline and/or submental neck mass despite its rarity, and the importance of a full workup for an unusual neck mass such as this one in order to avoid misdiagnosis. It also serves as another example that to provide the best management plan and optimise patient outcomes for head and neck cancers, referral to a regional subspecialty multidisciplinary team (MDT) is required.

Early diagnosis of oral cancer is critical to improve the survival rate of patients. Raman spectroscopy, a non-invasive spectroscopic technique, has shown potential in identifying early-stage oral cancer biomarkers in the oral cavity environment. However, inherently weak signals necessitate highly sensitive detectors, which restricts widespread usage due to high setup costs. In this research, the fabrication and assembly of a customised Raman system that can adapt three different configurations for the in vivo and ex vivo analysis is reported. This novel design will help in reducing the cost required to have multiple Raman instruments specific for a given application. First, we demonstrated the capability of a customized microscope for acquiring Raman signals from a single cell with high signal-to-noise ratio. Generally, when working with liquid samples with low concentration of analytes (such as saliva) under a microscope, excitation light interacts with a small sample volume, which may not be representative of whole sample. To address this issue, we have designed a novel long-path transmission set-up, which was found to be sensitive towards low concentration of analytes in aqueous solution. We further demonstrated that the same Raman system can be incorporated with the multimodal fibre optical probe to collect in vivo data from oral tissues. In summary, this flexible, portable, multi-configuration Raman system has the potential to provide a cost-effective solution for complete screening of precancer oral lesions.

There is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC. This was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. On univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95

BACKGROUND:Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS:In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS:Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION:Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING:None.

Non-conventional laryngeal malignancies (NSCC) often have limited published data to guide management despite individual histopathological subtypes often exhibiting heterogeneous behaviour, characteristics, and treatment responses compared to laryngeal squamous cell carcinoma (SCC). This study aimed to compare oncological outcomes with SCC, specifically disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Secondary objectives were to compare treatment differences and perform a state of the art review. This was a multicentre retrospective cohort study at four tertiary head and neck centres. Survival outcomes between NSCC and SCC patients were analysed with Kaplan–Meier curves and compared by log rank testing. Univariate Cox regression analysis was performed to predict survival by histopathological subgroup, T-stage, N-stage and M-stage. There were no significant differences in 3-year DFS (p = 0.499), DSS (p = 0.329), OS (p = 0.360) or Kaplan Meier survival curves (DSS/OS) between SCC and overall NSCC groups. However, univariate Cox regression analysis identified “rare” histopathologies (mostly small cell carcinoma) to be predictive of less favourable OS (p = 0.035) but this result was not observed for other NSCC histopathological subgroups. N-stage (p = 0.027) and M-stage (p = 0.048) also predicted OS for NSCC malignancies. Significant differences in treatment modalities were identified with treatment of NSCC typically involving surgical resection and SCC often managed non-surgically (e.g., primary radiotherapy). Although overall NSCC is managed differently compared to SCC, there do not appear to be differences in survival outcomes between these groups. N-stage and M-stage appear to be more predictive of OS than histopathology than many NSCC subtypes.