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The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.

Purpose: Robotic surgical techniques have transformed many surgical specialties however robotic techniques and applications have been much more limited in ophthalmology. This study aims to evaluate the feasibility of robotic assisted orbital surgery using a single-port novel robotic platform, the da Vinci SP., Methods: A series of orbital procedures were performed in cadaveric specimens utilizing the da Vinci SP robotic system. The procedures performed included lacrimal gland dissection and biopsy, medial and lateral orbital wall dissections, enucleation, and lid-sparing orbital exenteration. Successful completion of each procedure was defined by the operating surgeon and was considered the primary outcome and marker of feasibility., Results: Seven cadaveric procedures were performed in 3 cadaveric specimens. All 7 procedures were completed successfully without complication. Setup optimization occurred throughout the study and setup and operative times were acceptable. Three instrument arms and 1 endoscope were utilized throughout the study allowing 3 arm operating and dynamic retraction. Instrument size was found to limit surgical access and precision particular at the orbital apex., Conclusions: This preclinical study demonstrates that the da Vinci SP can be utilized within the orbit and is feasible for several applications. Robotic surgical systems offer significant advantages over conventional techniques and should be embraced. However, current commercially available robotic platforms are not optimized for the orbit and have their limitations although they may be suitable for some clinical applications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Orbital surgery benefits from well-designed instrumentation that offers gentle tissue manipulation, high manoeuvrability and control. Nevertheless, in confined spaces, tissue manipulation must be accomplished with exceptionally high accuracy and precision. This is where robotic surgery offers an advantage. We aimed to evaluate a robotic-assisted surgical system's feasibility, safety and outcome in assisting tumour clearance., Patients and Methods: A case series of patients with advanced periocular tumours undergoing robotic-assisted globe-sparing resection was performed using the DaVinci XI system (Intuitive Surgical, Inc). Institutional ethics and multidisciplinary approval were sought in all cases., Results: Four patients with advanced periocular tumours underwent robotic-assisted orbital surgery at a mean age of 63 years (range 42-86). Two patients were diagnosed with squamous cell carcinoma, and two had basal cell carcinoma. One patient was found to have positive lymph nodes at the time of surgery and underwent simultaneous parotidectomy and lymph node clearance. Clear resection of the primary tumour was achieved in all patients; three patients underwent further resection due to narrow margins prior to reconstruction. Patients were follow-up for at least one year, and three remained disease-free. One patient with pre-existing extra-orbital disease developed metastatic disease four months post-op. All patients preserved vision peri-operatively, with no complaints of diplopia. Moderate ocular surface disease was noted in two patients., Conclusion: Our series highlights the potential advantage of three-dimensional optics, multi-directional instrumentation and motion scaling technology to achieve globe-sparing tumour resection in advanced periocular tumours. However, further robotic instrumentation development is required for orbital surgery., (© 2024. The Author(s).)

Purpose: Transoral robotic surgery is well established in the treatment paradigm of oropharyngeal pathology. The Versius Surgical System (CMR Surgical) is a robotic platform in clinical use in multiple specialities but is currently untested in the head and neck. This study utilises the IDEAL framework of surgical innovation to prospectively evaluate and report a first in human clinical experience and single centre case series of transoral robotic surgery (TORS) with Versius., Methods: Following IDEAL framework stages 1 and 2a, the study evaluated Versius to perform first in human TORS before transitioning from benign to malignant cases. Iterative adjustments were made to system setup, instrumentation, and technique, recorded in accordance with IDEAL recommendations. Evaluation criteria included successful procedure completion, setup time, operative time, complications, and subjective impressions. Further evaluation of the system to perform four-arm surgery was conducted., Results: 30 TORS procedures were successfully completed (15 benign, 15 malignant) without intraoperative complication or conversion to open surgery. Setup time significantly decreased over the study period. Instrumentation challenges were identified, urging the need for TORS-specific instruments. The study introduced four-arm surgery, showcasing Versius' unique capabilities, although limitations in distal access were observed., Conclusions: TORS is feasible with the Versius Surgical System. The development of TORS-specific instruments would benefit performance and wider adoption of the system. 4-arm surgery is possible however further evaluation is required. Multicentre evaluation (IDEAL stage 2b) is recommended., (© 2024. The Author(s).)

Objectives: This study aims to assess the feasibility to perform transoral robotic surgery (TORS) with a new robotic platform, the Versius Surgical System (CMR Surgical, UK) in a preclinical cadaveric setting in accordance to stage 0 of the IDEAL-D framework., Design: IDEAL stage 0 preclinical assessment of the Versius Robotic System in TORS in human cadavers., Setting: All procedures were performed in a simulated operating theatre environment at a UK surgical training centre., Participants: 11 consultant head and neck surgeons from the UK, mainland Europe and the USA took part in TORS procedures on six human cadavers., Interventions: 3 key index procedures were assessed that represent the core surgical workload of TORS: lateral oropharyngectomy, tongue base resection and partial supraglottic laryngectomy., Main Outcome Measures: The primary outcome was the successful completion of each surgical procedure. Secondary outcomes included the optimisation of system setup, instrumentation and surgeon-reported outcomes for feasibility of each component procedural step., Results: 33 cadaveric procedures were performed and 32 were successfully completed. One supraglottic laryngectomy was not fully completed due to issues dividing the epiglottic cartilage with available instrumentation. Surgeon-reported outcomes met the minimal level of feasibility in all procedures and a consensus that it is feasible to perform TORS with Versius was reached. Available instrumentation was not representative of other robotic platforms used in TORS and further instrument optimisation is recommended before wider dissemination., Conclusions: It is feasible to perform TORS with the Versius Surgical System (CMR Surgical) within a pre-clinical cadaveric setting. Clinical evaluation is needed and appropriate with the system. Further instrument development and optimisation is desirable., Competing Interests: Competing interests: This study was funded by CMR Surgical Ltd. including providing access to laboratory space, cadavers and the robotic system. Mark Slack is a co-founder and current chief medical officer of CMR Surgical., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Pharyngeal leak (PL) and pharyngocutaneous fistula (PCF) are serious complications following total laryngectomy and their incidence is higher in the salvage setting. The aim of this study is to describe the accuracy of water soluble swallow (WSS) to rule out salivary postoperative leak after salvage total laryngectomy (STL) to expedite start of oral intake., Material and Methods: Retrospective study including patients undergoing STL between 2008 and 2021 at Guy's Hospital. WSS was routinely performed within 15 days post operation., Results: Sixty-six patients underwent STL. Nine developed clinically diagnosed PCF; one died before having WSS. Fifty-six patients underwent WSS post STL. WSS was performed within 15 days after STL when no postoperative complications occurred (76.8%). Among patients undergoing WSS with no clinical suspicion for fistula (56), PL was identified in 15 cases (26.8%). They were managed conservatively; PCF was avoided in 7(46.7%) cases. Three patients (7.3%) developed PCF after having started oral intake with a negative WSS. These three cases were further analysed, 2 cases where recorded at the beginning of the studied period when less experience was available possibly leading to incorrect results. Sensitivity and negative predictive value (NPV) for fistula prediction were 72.7% and 92.7%, respectively., Conclusion: Taking into account the high NPV of WSS, it is safe to start oral intake after negative WSS. Further studies to evaluate its accuracy earlier on after SLT are justified taking into account the results and the impact that delayed feeding has on patient's quality of life., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To review the clinical presentation, diagnosis, pathology and management strategies in a modern cohort of patients with thyroglossal duct cyst carcinoma., Study Design: Retrospective case series following PROCESS Guidelines., Setting: Comprehensive cancer centre., Methods: Data recorded included: gender, age at diagnosis, clinical presentation, thyroid function, diagnostic investigations, cytological results, final histology, staging and follow up status. The risk of malignancy in cytological analysis was stratified according to the Royal College of Pathologists classification in United Kingdom., Results: Twelve patients were included. The majority of patients (66.7%) presented with an isolated thyroglossal duct cyst. Only 4 patients had preoperative cytological suspicion of carcinoma (sensitivity: 33.3%). At the time of presentation all patients were euthyroid. Following diagnosis of malignancy, a total thyroidectomy was performed in all patients, with the exception of 2, who had a thyroglossal duct cyst carcinoma of less than 10mm. Among the 10 patients who underwent total thyroidectomy, 7 (70%) patients had proven carcinoma in the thyroid gland, 3 with deposits of less than 10mm. The average size of the thyroid cancer deposits was 7.2mm (1-20mm). With a mean follow-up of is 44 months (5-120), all patients were alive and free of recurrence at the end of the study period., Conclusion: Thyroglossal duct cyst carcinoma is a rare condition and its management should be discussed in a multidisciplinary meeting. As with differentiated thyroid cancer originating in the thyroid gland, it bears extraordinary survival rates. Accordingly, the management of these cancers has shifted towards a more conservative approach although its peculiarities must be taken into account: ease of extracystic invasion and possible different lymph node invasion., (Copyright © 2022 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The crosstalk between cancer and the tumour immune microenvironment (TIME) has attracted significant interest in the latest years because of its impact on cancer evolution and response to treatment. Despite this, cancer-specific tumour-TIME interactions and their mechanistic insights are still poorly understood., Methods: Here, we compute the significant interactions occurring between cancer-specific genetic drivers and five anti- and pro-tumour TIME features in 32 cancer types using Lasso regularised ordinal regression. Focusing on head and neck squamous cancer (HNSC), we rebuild the functional networks linking specific TIME driver alterations to the TIME state they associate with., Results: The 477 TIME drivers that we identify are multifunctional genes whose alterations are selected early in cancer evolution and recur across and within cancer types. Tumour suppressors and oncogenes have an opposite effect on the TIME and the overall anti-tumour TIME driver burden is predictive of response to immunotherapy. TIME driver alterations predict the immune profiles of HNSC molecular subtypes, and perturbations in keratinization, apoptosis and interferon signalling underpin specific driver-TIME interactions., Conclusions: Overall, our study delivers a comprehensive resource of TIME drivers, gives mechanistic insights into their immune-regulatory role, and provides an additional framework for patient prioritisation to immunotherapy. The full list of TIME drivers and associated properties are available at http://www.network-cancer-genes.org ., (© 2023. The Author(s).)

Background: Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues., Methods: We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1-4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×10 7 -1×10 9 T4 + T-cells, administered without prior lymphodepletion., Results: Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4 + T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product., Conclusions: These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC., Competing Interests: Competing interests: JM is founding scientist, shareholder in and chief scientific officer of Leucid Bio. FF is chief scientific officer of Virocell Biologics. AA and DMD are currently employees of Leucid Bio. SP is chief medical officer of Enara Bio. All other authors declared no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: Numerous factors are considered to impact on the rate of complications during salvage total laryngectomy procedures. Neck dissection could be one of these factors. This study analysed the pattern of lymph node metastasis and rate of occult neck disease during salvage total laryngectomy as well as the impact of neck dissection on survival and complication rates., Method: This was a retrospective analysis of a prospectively maintained laryngectomy database in two large tertiary teaching hospitals., Results: The rate of occult neck disease was 11.1 per cent. Most cases with occult neck disease had rT 4 disease. Patients with complications, advanced tumour stage and positive margins had a significant decrease in overall survival. Patients receiving elective neck dissection did not have any survival benefit. Positron emission tomography-computed tomography showed a very high specificity and negative predictive value., Conclusion: According to the low risk of occult neck disease when using contemporary imaging techniques as well as the lack of impact on survival, conservative management of the neck should be considered for crT 1 -T 3 recurrence.

Objectives: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]., Materials and Methods: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS)., Results: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11)., Conclusion: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS., (© 2021 Wiley Periodicals LLC.)

Background: The introduction of transoral robotic surgery into routine management of patients is complex. It involves organisational, logistical and clinical challenges. This study presents our experience of implementing such a programme and provides a blueprint for other centres willing to establish similar services., Methods: Implementation of the robotic surgery programme focused on several key domains: training, logistics, governance, multidisciplinary team awareness, pre-operative imaging, anaesthesia, post-operative care, finance, patient selection and consent. Programme outcomes were evaluated by assessing operative outcomes of the first 117 procedures performed., Results: The success of the transoral robotic surgery programme has been possible because of the scrupulous planning phase before the first procedure, and the time invested on team awareness and training., Conclusion: Implementation of a new transoral robotic surgery service has led to: the development of a dedicated transoral robotic surgery patient care protocol, the performance of progressively more complex procedures, the inclusion of transoral robotic surgery training and the establishment of several research projects.

Objective: This review assesses the effect on intra- and postoperative patient outcomes of the timing of neck dissection in relation to transoral surgery. Outcome measures include postoperative bleeding, intra- and postoperative fistula formation, and disease-specific and overall survival., Data Sources: A search was conducted across the MEDLINE, Embase, US National Library of Medicine, and Cochrane databases with search terms in July 2021., Review Methods: Articles that conformed with specified inclusion criteria were included. Included articles were scanned for bias with the ROBINS-I tool., Results: Nineteen articles were selected for qualitative analysis, including 546 patients who had neck dissection in conjunction with transoral robotic surgery/transoral laser microsurgery (TORS/TLM). Seventy-one (18%) patients had neck dissection prior to TORS/TLM, 39 (10%) had neck dissection performed after TORS/TLM, and 281 (72%) had concurrent procedures. In patients with neck dissection before TORS/TLM, 3% experienced major postoperative bleeding, and fistula rates were 0%. In the cohort with neck dissection after TORS/TLM, 3% experienced minor postoperative hemorrhage, and 8% had intraoperative fistulae. In the concurrent cohort of patients, 1% had major postoperative bleeds and 0.3% had minor bleeds, while 4% developed intraoperative fistulas and 0.3% developed postoperative fistulas., Conclusion: Current evidence indicated that there appears to be no correlation between timing of neck dissection and complications. This systematic review found insufficient data to comment on whether the timing of neck dissection in relation to TORS/TLM affects the outcomes of patients., (© The Authors 2022.)

Objective: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC)., Methods: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London)., Results: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [ p = 0.058] and 40% vs 8% [ p = 0.025]). Multivariate logistic regression analyses confirmed our data ( p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different ( p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%)., Conclusions: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Objective: Management of recurrent laryngeal cancer presents a major challenge, and salvage laryngectomy is complicated by previous oncologic treatments. Thyroidectomy as part of salvage laryngectomy adds a nonnegligible degree of morbidity. The purpose of this study is to assess the rate of thyroid gland invasion in patients undergoing salvage laryngectomy to determine relevant predictive factors., Study Design: Case series with chart review., Setting: Department of Otorhinolaryngology, Head and Neck Surgery, Guy's Hospital, London, United Kingdom., Methods: A retrospective review of patients undergoing salvage laryngectomy between 2009 and 2019 was undertaken. Preoperative cross-sectional imaging and histopathological analysis were performed to define evidence and predictors of thyroid gland invasion (TGI)., Results: Fifty-one patients had salvage laryngectomy. Histological evidence of TGI was found in 4 patients (7.8%). No significant relationship was found between histological TGI and subsite of primary carcinoma, degree of differentiation, T staging, or radiological TGI. Preoperative computed tomography had a high negative predictive value for TGI., Conclusion: Thyroidectomy should be carefully considered in patients undergoing salvage laryngectomy, and its extent should be defined on an individual basis. Total thyroidectomy should not routinely be performed in salvage laryngectomy or pharyngolaryngectomy in patients with no preoperative radiological evidence of TGI on cross-sectional imaging, unless there is intraoperative evidence of TGI.

Objectives: The use of transoral robotic surgery (TORS), transoral laser microsurgery (TLM) and more recently reported transoral endoscopic electrocautery (TOEC) in identifying the primary cancer in head and neck Carcinoma Unknown Primary (CUP) patients have gained popularity. This review aims to assess the effectiveness of TORS, TLM and TOEC., Materials & Methods: A systematic review and meta-analysis was carried out. EMBASE, MEDLINE and CINAHL databases were searched from inception to September 2020. All primary studies were considered for inclusion. Primary outcome measure was detection rates of primary cancer of the different techniques. Secondary outcome measures were complications and length of hospital stay., Results: 289 studies were identified of which 30 met the inclusion criteria. The primary cancer was identified in 567 /777 patients (pooled results was 64% (95% CI 54-73). The primary identification rates were 45% and 32% in lingual (n = 273) and palatine tonsillectomy (n = 118) respectively. The primary cancer identification rates by surgical techniques are: TORS was 60% (95% CI 49-70), TLM was 80% (95% CI 0.58, 1.01), TOEC was 41% (95% CI 0.05, 0.76). 529/777 (68%) tumours were Human Papilloma Virus (HPV) related. The pooled data of studies that reported on detection rates relating to HPV status were 178/216 (82%) for HPV +ve and 7/59 (12%) for HPV -ve tumours. Coefficient of variation results suggest heterogenous data for TORS and TLM. The commonest complication was haemorrhage (5.3%). The length of reported hospital stay ranged from 1.4 to 7 days., Conclusions: This is the largest systematic review in the subject. The quality of studies and heterogeneity of data limit conclusive findings. Lingual tonsillectomy is an effective procedure in CUP work up. Further larger, multicentre, prospective studies of PET CT negative CUP patients is needed to draw conclusive results., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. All rights reserved.)

Introduction: Locally advanced nonmelanoma skin cancers of the head and neck are well described in the current literature. However, data about clinical and survival outcomes are lacking. We present survival data from a tertiary head and neck cancer unit in London., Methods: A retrospective analysis of data collected from a single institution was conducted. All patients with locally advanced cutaneous scalp carcinomas invading the skull between 2011 and 2019 were included. Data included patient demographics, tumor, comorbidities, interventions, flap survival, and metal work exposure. Survival outcomes were examined using Kaplan-Meier analysis., Results: Twenty-three patients were identified. The mean age was 72 years. Eighteen patients were male, and 5 were female. Five patients were immunosuppressed. Nineteen patients underwent outer cortex drill-down/full-thickness calvarial resection, followed by reconstruction with free tissue transfer. Six patients had titanium mesh reconstruction after segmental skull resections. Three patients underwent further surgery because of exposed metalwork. Disease-free survival at 3 years after surgery was 60%., Conclusions: Locally advanced nonmelanoma skin cancers invading the bone are sporadic. There are little published data on clinical and survival outcomes in this group. Despite the nature of these skin lesions, a high degree of local control can be obtained by extensive surgical resection, outer table drill-down, and calvarial resection. We conclude that aggressive management of the bony invasion improves disease-free survival and improves local control., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Orbital exenteration is a radical oncological surgery that is usually indicated for advanced primary orbital tumors or invasion from local malignancy. We report a 5-year series from a tertiary head and neck center with particular focus on our ablative and reconstructive approach., Methods: We performed a clinicopathological review of patients referred to Guy's and St Thomas' NHS Foundation Trust Head and Neck multidisciplinary team for management input of an orbital malignancy during the period of 2013 to 2018. Cases involving local invasion from sinonasal malignancy were excluded. The reconstructive approach, perioperative complications, disease-free and overall survival were analyzed., Results: 27 patients were identified and of those treated surgically, a radical extended orbital exenteration was required in almost half (44.4%), with squamous cell carcinoma being the most common pathology (55.6%). A concurrent neck dissection and parotidectomy were commonly performed with confirmed or suspected regional disease, or in the presence of high-risk pathological features. This approach resulted in favourable 2-year overall survival in these advanced stage cases of 84.6% and disease-free survival of 73.2%, with 92% achieving a negative surgical margin. The majority of treated patients required a free flap reconstruction, especially when an extended exenteration defect or adjuvant treatment was anticipated. The anterolateral thigh flap was the most commonly used donor site, and we present our algorithm for reconstruction of these defects., Conclusions: A multidisciplinary approach to advanced orbital malignancy with a comprehensive approach to surgical resection and reconstruction results in favorable oncological outcomes and addresses functional and cosmetic patient rehabilitation.

Head and neck squamous cell carcinoma (HNSCC) has a significant impact on patients' quality of life and treatment can be associated with severe morbidity. Following completion of treatment, patients are followed up in order to detect potentially salvageable recurrences and to manage long-term toxicities. In recent years, a growing interest has been given to risk stratified follow-up interventions to prevent and detect recurrences and manage treatment toxicities in other tumour sites as well as to transfer some of that care to community services. We review the literature for HNSCC and propose a risk stratified follow up protocol to address these issues and assist clinicians in decision making. A shift in patterns of care is suggested in order to provide a basis to improve care for HNSCC patients after complete response to primary treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7., Material and Methods: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months., Results: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis., Conclusion: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The coronavirus disease 2019 pandemic resulted in the cessation of elective surgery. The continued provision of complex head and neck cancer surgery was extremely variable, with some UK centres not performing any cancer surgery. During the pandemic, Guy's and St Thomas' NHS Foundation Trust received high numbers of coronavirus disease 2019 admissions. This paper presents our experience of elective complex major head and neck cancer surgery throughout the pandemic., Methods: A head and neck cancer surgery hub was set up that provided a co-ordinated managed care pathway for cancer patients during the pandemic; the Guy's Cancer Centre provided a separate, self-enclosed coronavirus-free environment within the hospital campus., Results: Sixty-nine head and neck cancer patients were operated on in two months, and 13 patients had a microvascular free tissue transfer. Nosocomial infection with coronavirus disease 2019 was detected in two cases (3 per cent), neither required critical care unit admission. Both patients made a complete recovery and were discharged home. There were no deaths., Conclusion: Performing major head and neck surgery, including free flap surgery, is possible during the pandemic; however, significant changes to conventional practice are required to achieve desirable patient outcomes.

Background: Fourth branchial apparatus anomalies, are rare clinical entities, and present as complex cysts, sinuses and fistulae in the neck that can be difficult to manage., Methods: This is a retrospective review of a series of consecutive patients with fourth branchial apparatus anomalies treated at Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, from Apr 2014 to Nov 2019., Results: Ten patients with fourth branchial apparatus anomalies were identified, including 8 patients with fourth branchial fistula, and 2 patients with fourth branchial pouch sinus. There were 6 female patients and 4 male patients. Their age was from 6 years old to 39 years old (average age 20.4 years old, median age was 21 years old). All 8 fistulae were on the left side, while 2 pouch sinuses were both on the right side. Pre-operative examination with fiberoptic laryngoscope, barium swallow X-ray, CT or MRI identified internal orifice at pyriform fossa apex in 8 (80%) patients. All patients underwent challenging surgical resection by the senior author. Intra-operative direct laryngoscope confirmed or identified internal orifice in 9 (90%) patients. The tracts were all followed to the vicinity of inferior cornu of the thyroid cartilage and the cricothyroid space. Complete resection of cervical lesions and their attachment to hypopharynx were achieved in 9 cases. No complication occurred. One recurrence was detected, in the only patient whose internal orifice could not be located pre- or intra-operatively, and the hypopharyngeal attachment could not be removed., Conclusions: Direct laryngoscopy under general anesthesia is a reliable method of diagnosis for the fourth branchial apparatus anomalies. Complete surgical removal of fourth branchial apparatus anomalies, including their hypopharyngeal attachment, is the treatment of choice, and the key to prevent recurrence.

Three-dimensional (3D) image reconstruction of tumors based on serial histological sectioning is one of the most powerful methods for accurate high-resolution visualization of tumor structures. However, 3D histological reconstruction of whole tumor has not yet been achieved. We established a high-resolution 3D model of molecular marked whole laryngeal cancer by optimizing the currently available techniques. A series of 5,388 HE stained or immunohistochemically stained whole light microscopic images (200 ×) were acquired (15.61 TB).The data set of block-face images (96.2 GB) was also captured. Direct volume rendering of serial 6.25 × light microscopy images did not demonstrate the major characteristics of the laryngeal cancer as expected. Based on fusion of two datasets, the accurate boundary of laryngeal tumor bulk was visualized in an anatomically realistic context. In the regions of interest, micro tumor structure, budding, cell proliferation and tumor lymph vessels were well represented in 3D after segmentation, which highlighted the advantages of 3D reconstruction of light microscopy images. In conclusion, generating 3D digital histopathological images of a whole solid tumor based on current technology is feasible. However, data mining strategy should be developed for complete utilization of the large amount of data generated.

Objective: The global coronavirus disease 2019 (COVID-19) pandemic has necessitated rapid alterations to diagnostic pathways for head and neck cancer patients that aim to reduce risk to patients (exposure to the hospital environment) and staff (aerosol-generating procedures). Transoral fine needle aspiration cytology offers a low-risk means of rapidly diagnosing patients with oral cavity or oropharyngeal lesions. The technique was utilised in selected patients at our institution during the pandemic. The outcomes are considered in this study., Method: Diagnostic outcomes were retrospectively evaluated for a series of patients undergoing transoral fine needle aspiration cytology of oral cavity and oropharyngeal lesions during the COVID-19 pandemic., Results: Five patients underwent transoral fine needle aspiration cytology, yielding lesional material in 100 per cent, with cell blocks providing additional information. In one case, excision biopsy of a lymphoproliferative lesion was required for final diagnosis., Conclusion: Transoral fine needle aspiration cytology can provide rapid diagnosis in patients with oral cavity and oropharyngeal lesions. Whilst limitations exist (including tolerability and lesion location), the technique offers significant advantages pertinent to the COVID-19 era, and could be employed in the future to obviate diagnostic surgery in selected patients.

Purpose: To evaluate whether the 8th staging system is a better discriminator of overall survival (OS) than the 7th edition for oropharyngeal cancer patients after definitive (chemo)radiotherapy (CRT)., Material and Methods: Data from oropharyngeal cancer patients treated with CRT with curative intent between 2010 and 2016 at Guy's and St Thomas' Hospitals were reviewed. Human papillomavirus (HPV) status was ascertained in all cases. Patients were staged using the 7th edition and the 8th edition TNM staging system. Demographics, tumor characteristics and treatment response data were included in univariate and multivariate analysis for OS. OS and disease-free survival (DFS) were estimated using the Kaplan-Meier method. In addition, a multivariate survival Cox regression analysis of several clinical variables was performed., Results: A total of 273 patients were included. The median follow-up was 4.7 years. Overall 63 patients died. In multivariate analysis, HPV status, complete response at 3 months and ≤21 units/week alcohol were prognostic for OS. For the entire cohort, the 5-year OS and DFS rates were 78.1% (95% confidence interval CI 0.719-0.831) and 73.9% (95% CI 0.677-0.792), respectively. Better stratification of OS and DFS was recorded by 8th edition for the entire cohort. In HPV-positive cases, risk stratification based on tobacco smoking and nodal stage resulted in statistically higher discrimination in OS rates (5-year OS 90.7% in low risk patients and 84.6% in intermediate risk, p = 0.05) and DFS rates (5-year DFS 91.5% in low risk and 76.1% in intermediate risk, p = 0.001)., Conclusion: The 8th edition TNM staging system provides better OS stratification in oropharyngeal cancer after definitive CRT compared with the 7th edition. Other clinical variables, such as complete response at 3 months, alcohol and tobacco smoking, should also be considered in future classifications as they provide additional risk stratification information in both HPV-positive and HPV-negative disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To validate the use of neck dissection as part of the management of patients with parotid carcinomas, we retrospectively reviewed pathological and clinical data from the head and neck pathology archive at Guy's and St Thomas' Hospital on all patients who had primary parotid carcinomas resected between 1992 and 2014. The main outcome measure was the incidence of metastatic disease. A total of 54 of the 82 patients identified had neck dissections. Nodal metastases were detected in 10 with high-grade, invasive carcinoma ex-pleomorphic adenomas, two with salivary duct carcinomas, one with a high-grade adenocarcinoma not otherwise specified (NOS), one with an adenoid cystic carcinoma, and one with a high-grade acinic cell carcinoma. No metastases were found in those with a low-grade acinic cell carcinoma, low-grade mucoepidermoid carcinoma, epithelial-myoepithelial carcinoma, or non-invasive carcinoma ex-pleomorphic adenoma. The findings of this study support the use of routine neck dissection for the treatment of high-grade, invasive carcinoma ex-pleomorphic adenoma, salivary duct carcinoma, high-grade adenocarcinoma NOS, adenoid cystic carcinoma, and high-grade acinic cell carcinoma., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The purpose of this study was to review our recent experience of salvage surgery, comparing larynx and oropharynx recurrence patterns., Methods: A single centre, retrospective review of salvage surgery for recurrent head and neck cancer including patients between 2008 and 2016., Results: 61 patients were identified, 36 underwent salvage laryngectomy and 25 received oropharyngeal resections. The median overall survival of oropharyngeal recurrent tumors was 26 months (95% CI 15-118 months) and for laryngeal tumors was 23 months (95% CI 11-38 months), p = 0.1008. There was a significant overall survival benefit in patients with negative resection margin. The median survival in the negative margin group was 38 months (95% CI 25-108 months) compared to the positive margin group, 9 months (95% CI 5-15 months), p < 0.0001., Conclusion: Survival results following surgical salvage in the larynx and oropharynx appear to be similarly poor. Those patients with clear margins appear to have a significantly better prognosis.

Aim: To analyse the maximum standardised uptake value (SUVmax) ratio between tonsils in patients with and without tonsillar carcinoma to determine useful diagnostic thresholds., Materials and Methods: Positron-emission tomography (PET)/computed tomography (CT) examinations of patients with suspected head and neck squamous cell carcinoma (SCC) and controls from April 2013 to September 2016 were reviewed retrospectively. Tonsillar SUVmax ratios (ipsilateral/contralateral for malignant tonsils, maximum/minimum for patients without [controls]) were calculated and used to construct a receiver operating characteristic (ROC) curve., Results: Twenty-five patients had tonsillar carcinoma (mean SUVmax ratio of 2, range 0.89-5.4) and 86 patients acted as controls (mean SUVmax ratio of 1.1, range 1-1.5). Using the ROC, the most accurate SUVmax ratio for identifying malignancy was >1.2 (77% sensitivity, 86% specificity). A potentially more clinically useful SUVmax ratio is ≥1.6 with 62% sensitivity and 100% specificity., Conclusion: An SUVmax ratio between tonsils of ≥1.6 is highly suspicious for SCC and could be used to direct site of biopsy. Some malignant tonsils had normal FDG uptake; therefore, PET/CT should not be used to exclude tonsillar cancer. Minor asymmetrical uptake is frequently seen in non-malignant tonsils and does not necessarily require further investigation. Due to the single centre nature of this study and the recognised variation in SUV measurements between PET scans, other centres may need to develop their own cut-offs., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Following the inception of transoral robotic surgery (TORS) in 2005, the field of robotic head and neck surgery has undergone refinement and innovation. Optimizing patient outcome, preserving function, and limiting morbidity are the key drivers. The next leap forward is another generation of flexible robotic surgical systems. Several such systems are under clinical and preclinical evaluation. A new single-port (Sp) robotic surgical architecture is now available integrating three fully articulating instruments and a flexible three-dimensional high-definition camera delivered through a 25-mm cannula. Preclinical feasibility studies of the Sp in human cadaver and porcine models suggest improved application compared to existing platforms for oropharyngeal and nasopharyngeal resection. With 3-handed manipulation of tissue, traction and countertraction may be used to deliver a more precise surgical dissection of head and neck anatomy than is currently possible. The single-port design permits greater access and maneuverability for the bedside surgical assistant. An alternative currently available in clinical use includes the Flex® system using a robotic camera and manually controlled endoscopic instruments. The Cambridge Medical Robotics Versius system is undergoing preclinical evaluation for TORS and may offer a novel modular approach. All of these systems allow the head and neck surgeon to reach further beyond the upper aerodigestive tract with greater agility and precision, expanding the boundaries of minimal access head and neck surgery., (© 2018 S. Karger AG, Basel.)

Objectives: To analyse survival and toxicity outcomes in patients treated with primary intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma (OPSCC) in the era of routine human papilloma virus (HPV) testing., Design: Single-institution case series., Setting: Tertiary Head and Neck Cancer Unit., Participants: A total of 186 patients received IMRT (+/- chemotherapy) for radical primary treatment of OPSCC between March 2010 and December 2013. HPV status was available for 88% of cases. Median radiation dose was 65 Gy in 30 daily fractions. 90% of stage III/IV patients received concurrent chemotherapy or cetuximab., Main Outcome Measures: Overall, disease-free and disease-specific survival; rates of late xerostomia and dysphagia., Results: A total of 177 patients completed treatment (Stage I/II: 23; Stage III/IV: 154), with median follow-up of 26 months. Estimated 3-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) rates were 77.2% (70.5-83.9), 72.3% (65.4-79.2) and 80.2% (74.1-86.3). Estimated 3-year OS, DFS and DSS for HPV-positive patients were 90.9% (85.2-96.6), 87.9% (81.4-94.4) and 91.8% (86.3-97.3). A previously identified risk stratification method was validated, showing improved OS for low-risk over high-risk patients (HR 0.09, P < 0.001). The 2-year feeding tube retention rate was 6%, and 2-year grade ≥2 xerostomia rate was 38% (23% if mean contralateral parotid dose <24 Gy)., Conclusions: Outcomes with IMRT are favourable, particularly in the HPV-positive patient group. This data further supports the use of a previously described prognostication model that can be used to select patients for escalation/de-escalation clinical trials., (© 2016 John Wiley & Sons Ltd.)

Background: Sarcoma of the head and neck is a rare condition that poses significant challenges in management and often requires radical multimodality treatment., Objectives: This study aimed to analyse current clinical presentation, evaluation, management dilemmas and oncological outcomes., Methods: Computer records and case notes were analysed, and 39 patients were identified. Variables were compared using Pearson's chi-square test and the log-rank test, while survival outcomes were calculated using the Kaplan-Meier method., Results: The histopathological diagnosis was Kaposi sarcoma in 20.5 per cent of cases, chondrosarcoma in 15.3 per cent and osteosarcoma in 10.2 per cent. A range of other sarcomas were diagnosed in the remaining patients. The site of disease was most commonly sinonasal, followed by the oral cavity and larynx., Conclusion: Wide local excision with clear resection margins is essential to achieve local control and long-term survival. There is a need for cross-specialty collaboration in order to accrue the evidence which will be necessary to improve long-term outcomes.

Differentiated thyroid cancer (DTC) accounts for over 90 % of thyroid malignancies, and is frequently associated with central neck compartment nodal metastasis that requires a therapeutic central compartment neck dissection (CCND) for clinically evident nodes. Current knowledge on the expected lymph node yield from a CCND is limited, compared with data on the lateral neck. The aim of our study was to accurately quantify nodal yield from the cadaveric central neck compartment. Twenty-eight cadaveric necks were dissected and the central neck compartment was subdivided into four regions: pre-laryngeal (delphian), pre-tracheal, right and left para-tracheal regions. Each cadaver had a thyroid gland, which was also removed, and the CCND tissue in each compartment was processed and examined by a consultant histopathologist. Only lymphoid tissue with a defined microscopic fibrous capsule and subcapsular sinus was included in the node count. The median total lymph node count per cadaver was four (range 1-16), with a median of one node detectable in each para-tracheal region (range 0-7) and the pre-tracheal region (range 0-8). The median pre-laryngeal node count was 0 (range 0- 2). The average lymph node size across all compartments was 2.9 mm. This is the first European study to assess cadaveric central neck lymph nodes and establish baseline counts for nodal yield. If a prophylactic or therapeutic CCND is required during thyroid surgery, those involved in DTC management must recognise that there is a wide range, and low median yield of central neck compartment lymph nodes.

Objectives: To analyze clinical features, dosimetric parameters, and outcomes of osteoradionecrosis (ORN)., Study Design: Thirty-six patients with ORN who had been previously treated with radiotherapy (RT) were retrospectively identified between January 2009 and April 2014. ORN volumes were contoured on planning computed tomography (CT) scans. Near maximum dose (D2%), minimum dose (Dmin), mean dose (Dmean), and percentage of bone volume receiving 50 Gy (V50) were examined. Clinical and dosimetric variables were considered to compare ORN resolution versus ORN persistence., Results: Median interval time from end of RT to development of ORN was 6 months. Of the ORN cases, 61% were located in the mandible. Dmean to affected bone was 57.6 Gy, and 44% had a D2% 65 Gy or greater. Smoking was associated with ORN persistence on univariate analysis, but no factors were found to impact ORN resolution or progression on logistic regression., Conclusions: Prevention strategies for ORN development should be prioritized. Dose-volume parameters could have a role in preventing ORN., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the use of (18)F-FDG PET/CT as the principal investigation to assess tumour response, to determine the need for further surgery and to guide follow-up following radical chemoradiotherapy for stage III/IV oropharyngeal squamous cell carcinoma (OPSCC)., Methods: A retrospective analysis was undertaken in 146 patients treated at our centre with radical chemoradiotherapy for OPSCC and who had a PET/CT scan to assess response. According to the PET/CT findings, patients were divided into four groups and recommendations: (1) complete metabolic response (enter clinical follow-up); (2) low-level uptake only (follow-up PET/CT scan in 12 weeks); (3) residual uptake suspicious for residual disease (further investigation with or without neck dissection); and (4) new diagnosis of distant metastatic disease (palliative treatment options)., Results: The initial PET/CT scan was performed at a median of 12.4 weeks (range 4.3 - 21.7 weeks) following treatment. Overall sensitivity and specificity rates were 92.0 % (74.0 - 99.0 %) and 85 % (77.5 - 90.9 %). Of the 146 patients, 90 (62 %) had a complete response and had estimated 3-year overall and disease-free survival rates of 91.9 % (85.6 - 98.2 %) and 85.6 % (78.0 - 93.2 %), respectively, 17 (12 %) had residual low-level uptake only (with two having confirmed residual disease on subsequent PET/CT, both surgically salvaged), 30 (21 %) had suspicious residual uptake (12 proceeded to neck dissection; true positive rate at surgery 33 %). HPV-positive patients with reassuring PET/CT findings had an estimated 3-year progression-free survival rate of 91.7 % (85.2 - 98.2 %), compared with 66.2 % (41.5 - 90.9 %) of HPV-negative patients., Conclusion: A strategy of using PET/CT results alongside clinical examination to help select patients for salvage surgery appears successful. Despite a complete response on the 12-week PET/CT scan, HPV-negative patients have a significant risk of disease relapse in the following 2 years and further studies to assess whether surveillance imaging in this group could improve outcomes are warranted.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessment and management of patients with cancer of the oral cavity and the lip. Recommendations • Surgery remains the mainstay of management for oral cavity tumours. (R) • Tumour resection should be performed with a clinical clearance of 1 cm vital structures permitting. (R) • Elective neck treatment should be offered for all oral cavity tumours. (R) • Adjuvant radiochemotherapy in the presence of advanced neck disease or positive margins improves control rates. (R) • Early stage lip cancer can be treated equally well by surgery or radiation therapy. (R).

Background: Accurate alignment between histopathology slices and positron emission tomography (PET) images is important for radiopharmaceutical validation studies. Limited data is available on the registration accuracy that can be achieved between PET and histopathology slices acquired under routine pathology conditions where slices may be non-parallel, non-contiguously cut and of standard block size. The purpose of this study was to demonstrate a method for aligning PET images and histopathology slices acquired from patients with laryngeal cancer and to assess the registration accuracy obtained under these conditions., Methods: Six subjects with laryngeal cancer underwent a (64)Cu-copper-II-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) PET computed tomography (CT) scan prior to total laryngectomy. Sea urchin spines were inserted into the pathology specimen to act as fiducial markers. The specimen was fixed in formalin, as per standard histopathology operating procedures, and was then CT scanned and cut into millimetre-thick tissue slices. A subset of the tissue slices that included both tumour and fiducial markers was taken and embedded in paraffin blocks. Subsequently, microtome sectioning and haematoxylin and eosin staining were performed to produce 5-μm-thick tissue sections for microscopic digitisation. A series of rigid registration procedures was performed between the different imaging modalities (PET; in vivo CT-i.e. the CT component of the PET-CT; ex vivo CT; histology slices) with the ex vivo CT serving as the reference image. In vivo and ex vivo CTs were registered using landmark-based registration. Histopathology and ex vivo CT images were aligned using the sea urchin spines with additional anatomical landmarks where available. Registration errors were estimated using a leave-one-out strategy for in vivo to ex vivo CT and were estimated from the RMS landmark accuracy for histopathology to ex vivo CT., Results: The mean ± SD accuracy for registration of the in vivo to ex vivo CT images was 2.66 ± 0.66 mm, and the accuracy for registration of histopathology to ex vivo CT was 0.86 ± 0.41 mm. Estimating the PET to in vivo CT registration accuracy to equal the PET-CT alignment accuracy of 1 mm resulted in an overall average registration error between PET and histopathology slices of 3.0 ± 0.7 mm., Conclusions: We have developed a registration method to align PET images and histopathology slices with an accuracy comparable to the spatial resolution of the PET images.

Objective: To assess the prevalence and pathological nature of incidental focal thyroid uptake on (18)F-FDG (2-[(18)F]-fluoro-2-deoxy-D-glucose) PET (positron emission tomography) and examine the role of the maximum standardised uptake value (SUVmax) to differentiate benign from malignant thyroid pathology., Material and Methods: (18)F-FDG PET reports were retrospectively reviewed. Incidental focal tracer uptake in the thyroid was noted in 147 patients (0.5%). Patients with known primary thyroid malignancy were excluded. The final diagnosis was made following ultrasonography of the neck, fine-needle aspiration cytology (FNAC) or histopathology of the surgically resected specimen where surgery was indicated. A Mann-Whitney U test was used to compare the SUVmax of benign and malignant thyroid pathology. Receiver operating characteristic (ROC) analysis was performed to identify an SUVmax cutoff in differentiating benign from malignant pathology., Results: A final diagnosis was achieved in 47/147 (32%) of the patients. The diagnoses included benign lesions in 36 patients and malignancy in 9 patients. In 2 patients, FNAC demonstrated indeterminate follicular lesions; however, surgical excision was not performed. There was a highly significant difference in the mean SUVmax of malignant focal thyroid uptake (15.7 ± 5.9) compared to that of benign lesions (7.1 ± 6.8) with a p value of 0.000123. An SUVmax of 9.1 achieved a sensitivity of 81.6%, specificity of 100% and area under the curve of 0.915 in the ROC analysis differentiating benign from malignant disease., Conclusion: The malignancy potential of incidental focal thyroid uptake remains high and warrants prompt and appropriate follow-up by the clinician. The SUVmax may aid in further characterisation of the lesion and its management.