Mutation detection in saliva from oral cancer patients.

OBJECTIVES: The incidence of head and neck squamous cell carcinoma (HNSCC) continues to increase and although advances have been made in treatment, it still has a poor overall survival with local relapse being common. Conventional imaging methods are not efficient at detecting recurrence at an early stage when still potentially curable. The aim of this study was to test the feasibility of using saliva to detect the presence of oral squamous cell carcinoma (OSCC) and to provide additional evidence for the potential of this approach. MATERIALS AND METHODS: Fresh tumor, whole blood and saliva were collected from patients with OSCC before treatment. Whole exome sequencing (WES) or gene panel sequencing of tumor DNA was performed to identify somatic mutations in tumors and to select genes for performing gene panel sequencing on saliva samples. RESULTS: The most commonly mutated genes identified in primary tumors by DNA sequencing were TP53 and FAT1. Gene panel sequencing of paired saliva samples detected tumor derived mutations in 9 of 11 (82%) patients. The mean variant allele frequency for the mutations detected in saliva was 0.025 (range 0.004 - 0.061). CONCLUSION: Somatic tumor mutations can be detected in saliva with high frequency in OSCC irrespective of site or stage of disease using a limited panel of genes. This work provides additional evidence for the suitability of using saliva as liquid biopsy in OSCC and has the potential to improve early detection of recurrence in OSCC. Trials are currently underway comparing this approach to standard imaging techniques.

Incidental Thyroid Tissue in Sentinel Nodes From Oral Squamous Cell Carcinoma.

OBJECTIVE: Sentinel node biopsy (SNB) is a surgical staging test in which sentinel nodes (SNs) undergo intensive histological analysis. SNB diagnoses early cancer spread, but can also reveal unexpected findings within the SNs. We review cases of incidental thyroid cells (TC) found in SNs from patients with oral squamous cell carcinoma (OSCC) to assess the prevalence of TC, and the clinical significance of these. METHODS: Multicenter retrospective review of SNB performed for cT1-T2N0 OSCC. Incidental TC were identified by TTF-1 or thyroglobulin positivity. Anatomical location of nodes containing TC, TC morphology, and ongoing management/follow up of this incidental finding was recorded. Neck dissections performed during the same period were reviewed to establish the expected incidence of TC in neck nodes without serial sectioning analysis. RESULTS: 278 SNB cases were reviewed. Ten procedures detected TC in nine patients (10/278, 3.6%). During the same time period 725 neck dissections were performed, six containing TCs (6/725, 0.8%). One patient underwent SNB twice with TC identified on both occasions. Three patients had both OSCC metastasis and thyroid cells. All SNB patients with TC identified underwent thyroid USS with no primary tumours identified. Three patients underwent thyroidectomy, in all cases no primary thyroid tumour was found. CONCLUSION: Prevalence of incidental TC in SNs appears to be higher than that reported in neck dissections, these are not likely to be clinically relevant and can be managed on a conservative basis in the absence of clear metastatic features. LEVEL OF EVIDENCE: Multicentre retrospective cohort study, 3 Laryngoscope, 134:1278-1281, 2024.

Augmented reality presentation of the extracranial facial nerve: an innovation in parotid surgery.

Surgeons used to be unaware of the facial nerve's position during parotid surgery. Now, with special magnetic resonance imaging (MRI) sequences, it can be located and converted into a 3D model displayed on an augmented reality (AR) device for surgeons to study and manipulate. This study explores the accuracy and usefulness of the technique for the treatment of benign and malignant parotid tumours. A total of 20 patients with parotid tumours had 3-Tesla MRI scans, and their anatomical structures were segmented using Slicer software. The structures were imported into a Microsoft HoloLens 2® device, displayed in 3D, and shown to the patient for consent. Intraoperative video recording was used to record the position of the facial nerve in relation to the tumour. The predicted path of the nerve taken from the 3D model was combined with surgical observation and video recording in all cases. The imaging proved to have application in both benign and malignant disease. It also improved the process of informed patient consent. Three-dimensional MRI imaging of the facial nerve within the parotid gland and its display in a 3D model is an innovative technique for parotid surgery. Surgeons can now see the nerve's position and tailor their approach to each patient's tumour, providing personalised care. The technique eliminates the surgeon's blind spot and is a significant advantage in parotid surgery.

Systematic review of techniques used to validate the registration of augmented-reality images using a head-mounted device to navigate surgery.

Augmented-reality (AR) head-mounted devices (HMD) allow the wearer to have digital images superposed on to their field of vision. They are being used to superpose annotations on to the surgical field akin to a navigation system. This review examines published validation studies on HMD-AR systems, their reported protocols, and outcomes. The aim was to establish commonalities and an acceptable registration outcome. Multiple databases were systematically searched for relevant articles between January 2015 and January 2021. Studies that examined the registration of AR content using a HMD to guide surgery were eligible for inclusion. The country of origin, year of publication, medical specialty, HMD device, software, and method of registration, were recorded. A meta-analysis of the mean registration error was conducted. A total of 4784 papers were identified, of which 23 met the inclusion criteria. They included studies using HoloLens (Microsoft) (n = 22) and nVisor ST60 (NVIS Inc) (n = 1). Sixty-six per cent of studies were in hard tissue specialties. Eleven studies reported registration errors using pattern markers (mean (SD) 2.6 (1.8) mm), and four reported registration errors using surface markers (mean (SD) 3.8 (3.7) mm). Three studies reported registration errors using manual alignment (mean (SD) 2.2 (1.3) mm). The majority of studies in this review used in-house software with a variety of registration methods and reported errors. The mean registration error calculated in this study can be considered as a minimum acceptable standard. It should be taken into consideration when procedural applications are selected.

Extracapsular dissection (ECD) and extended ECD: description of the technique and outcome of treatment.

Over the last two decades the senior author has exclusively applied the technique of extracapsular dissection (ECD) and extended ECD to treat discrete, apparently benign parotid tumours. This article describes both techniques and evaluates their application. Simple principles are described to anticipate unexpected malignant tumours and manage lumps safely by wide excision. A retrospective analysis of 97 consecutive patients with discrete, apparently benign parotid lumps is presented. The tumours were classified using the European Salivary Gland Society (ESGS) classification for benign tumours of the parotid gland. The ECD or extended ECD technique was employed irrespective of tumour site or size. A review of patients was carried out after a minimum of six months post surgery by two independent clinicians. The mean (range) hospital stay was one (0-4) night (median 1). Complications were both modest and transient. The temporary facial nerve injury rate was 5/97 (6%). Other complications included haematoma (n=2), sialocele (n=2), and first-bite syndrome (n=2). Independent review post surgery demonstrated a mean Sunnybrook facial grading system score of 98/100 and a mean Stony Brook scar assessment score of 4.5/5. In this series 5/97 (5%) of discreet mobile lumps concealed a low-grade salivary cancer. Experience with the application of ECD in conjunction with its extended form in 97 consecutive patients with discrete parotid lumps is described. The technique is amenable to all parotid lumps, is not restricted by site or size, and has shown minimal morbidity. The risk of recurrent disease could not be addressed.

The use of mixed reality in dentistry.

Augmented reality (AR) was first described in the literature in the 1990s. It has been shown as a futuristic concept in television, film and media, and now in the twenty-first century has become a reality. AR is defined as an interactive experience of a real-world environment where the object that resides in the real world is enhanced by computer-generated perceptual information.Microsoft HoloLens is a mixed reality device which has the capability to provide a real-time, three-dimensional platform using multiple sensors and holographic processing to display information and even simulate a virtual world. With rapidly evolving technology and virtual learning on the increase, the HoloLens technology can be used as a vital tool for dental education and surgical planning. However, within dentistry at present, there is limited research regarding its benefits and potential.The authors would like to demonstrate the use of HoloLens in three common oral surgery procedures and how it can be used to distinguish anatomy and benefit surgical planning, aid in patient communication and play a role in dental education.

Outcomes of microsurgical free tissue transfer performed on international surgical collaborations in low-income and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Microsurgical free tissue transfer is the gold standard for reconstruction of significant soft tissue and bony defects following cancer resection and trauma. Many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources or training required to perform microsurgical procedures. Long-term international collaborations have been formed with annual reconstructive programmes conducting microsurgery. AIMS: To critically analyze outcomes of microsurgical free tissue transfer performed on international reconstructive collaborations in LMICs. METHODS: PRISMA-compliant systematic review and meta-analysis of outcomes for free tissue transfer performed during international collaborations in LMICs using an inverse variance model. The study protocol was published prospectively and registered with PROSPERO (ID: CRD42021225613). RESULTS: Seven studies, included 290 flaps on 284 patients. The most common sites requiring reconstruction were Head and neck (53% (n = 153)) and lower limb (7.9% (n = 23)) were lower limb reconstruction. The most common free flaps were radial forearm (22%; n = 64) and anterolateral thigh (18%; n = 51). Total Flap Failure rate was 3.8% (n = 13; 95% confidence interval (CI) = 1.9-6.3%) Overall complication rate was 38% (95% CI =27-48%), with 19% of flaps requiring emergency return to theatre (95% CI =14-26%). Flap salvage was successful in 52% of take-backs (95% CI =15% - 88%). CONCLUSIONS: Free flaps performed during international surgical collaborations in LMICs have comparable failure rates to those performed in higher-income settings. However, there are higher complication and take-back rates. This should be taken into account when planning international collaborations. These results should help preoperative counselling and the consent process.

Centralised pathology service for sentinel node biopsy in oral cavity cancer: The Southeast England Consortium experience.

BACKGROUND: Sentinel lymph node biopsy is an increasingly recognised option for accurate staging and subsequent management of the clinically negative neck in early stage oral cavity squamous cell carcinoma. However, the technique is currently underused due to several logistic constraints including increased burden on pathology services. Here, we describe the feasibility of an outsourced centralised pathology processing and reporting service for sentinel lymph node biopsies in oral cavity squamous cell carcinoma. PATIENTS AND METHODS: The Southeast England Consortium comprises four surgical centres utilising a central pathology service. Consecutive cases between January 2016 and February 2020 were retrospectively evaluated for survival outcomes and laboratory turnaround times. RESULTS: Twenty-eight per cent from a cohort of 139 patients had positive sentinel nodes. There was a trend towards greater overall, disease-free and disease-specific survival (OS, DFS and DSS, respectively) in sentinel node negative compared to sentinel node positive patients, but these differences were not statistically significant. The sensitivity, negative predictive value and false negative rate were 92.8%, 97.0% and 6.8%, respectively. The mean and mode laboratory TAT were 5 and 4 working days, respectively. CONCLUSION: An outsourced centralised pathology service is a feasible option to widen the availability of sentinel node biopsy in oral cavity squamous cell carcinoma.

The impact of the COVID-19 pandemic on international reconstructive collaborations in Africa.

Background: The SARS-CoV-2 (COVID-19) pandemic has catalysed a widespread humanitarian crisis in many low- and middle-income countries around the world, with many African nations significantly impacted. The aim of this study was to quantify the impact of the COVID-19 pandemic on the planning and provision of international reconstructive collaborations in Africa. Methods: An anonymous, 14-question, multiple choice questionnaire was sent to 27 non-governmental organisations who regularly perform reconstructive surgery in Africa. The survey was open to responses for four weeks, closing on the 7th of March 2021. A single reminder was sent out at 2 weeks. The survey covered four key domains: (1) NGO demographics; (2) the impact of COVID-19 on patient follow-up; (3) barriers to the safe provision of international surgical collaborations during COVID-19; (4) the impact of COVID-19 on NGO funding. Results: A total of ten reconstructive NGOs completed the survey (response rate, 37%). Ethiopia (n = 5) and Tanzania (n = 4) were the countries where most collaborations took place. Plastic, reconstructive and burns surgery was the most common sub-speciality (n = 7). For NGOs that did not have a year-round presence in country (n = 8), only one NGO was able to perform reconstructive surgery in Africa during the pandemic. The most common barrier identified was travel restrictions (within country, n = 8 or country entry-exit, n = 7). Pre-pandemic, 1547 to ≥ 1800 patients received reconstructive surgery on international surgical collaborations. After the outbreak, 70% of NGOs surveyed had treated no patients, with approximately 1405 to ≥ 1640 patients left untreated over the last year. Conclusions: The COVID-19 pandemic has placed huge pressures on health services and their delivery across the globe. This theme has extended into international surgical collaborations leading to increased unmet surgical needs in low- and middle-income countries.Level of evidence: Not gradable. Supplementary Information: The online version contains supplementary material available at 10.1007/s00238-021-01892-4.

Single-photon emission computed tomography (SPECT/CT) images of sentinel node distribution in oral cancer.

This audit describes the lymphatic flow from oral tumours seen on single-photon emission computed tomography (SPECT/CT) to help sentinel node (SN) identification. A total of 95 consecutive sentinel node biopsies (SNB) were taken between 2010 and 2019. Eligibility criteria for SNB were patients over 18 years of age with a T1-T2 oral or oropharyngeal squamous cell carcinoma and an N0 neck. SNs collect at high-frequency sites irrespective of the primary tumour (22.7% level Ib; 64.8% levels II/III; and 7.6% level IV), but with individual variation. Radiotracer activity did not influence the number of nodes identified, and metastatic deposits were found in the hottest nodes. SNs occur at the same high-frequency locations in the neck, so familiarity with anatomical detail may reduce false-negative results.

Increasing the Reach of the Submental Artery Island Flap Using the Y-V Pedicle Lengthening Technique: Video and Technical Considerations.

SUMMARY: This article and instructional video detail a step-by-step approach to performing the Y-V venous pedicle lengthening technique, which can be used to increase the reach of the submental artery island flap by up to 5 cm, permitting reconstruction of soft-tissue defects of the middle and upper thirds of the face. This technique can also be used to maximize advancement of many common flaps around the body, including the medial plantar and lateral arm flaps.

Protocol for a systematic review of outcomes from microsurgical free-tissue transfer performed on short-term collaborative surgical trips in low-income and middle-income countries.

BACKGROUND: In many units around the world, microsurgical free-tissue transfer represents the gold standard for reconstruction of significant soft tissue defects following cancer, trauma or infection. However, many reconstructive units in low-income and middle-income countries (LMICs) do not yet have access to the resources, infrastructure or training required to perform any microsurgical procedures. Long-term international collaborations have been formed with annual short-term reconstructive missions conducting microsurgery. In the first instance, these provide reconstructive surgery to those who need it. In the longer-term, they offer an opportunity for teaching and the development of sustainable local services. METHODS: A PRISMA-compliant systematic review and meta-analysis will be performed. A comprehensive, predetermined search strategy will be applied to the MEDLINE and Embase electronic databases from inception to August 2021. All clinical studies presenting sufficient data on free-tissue transfer performed on short-term collaborative surgical trips (STCSTs) in LMICs will be eligible for inclusion. The primary outcomes are rate of free flap failure, rate of emergency return to theatre for free flap salvage and successful salvage rate. The secondary outcomes include postoperative complications, cost effectiveness, impact on training, burden of disease, legacy and any functional or patient reported outcome measures. Screening of studies, data extraction and assessments of study quality and bias will be conducted by two authors. Individual study quality will be assessed according to the Oxford Evidence-based Medicine Scales of Evidence 2, and risk of bias using either the 'Revised Cochrane risk of bias tool for randomized trials' (Rob2), the 'Risk of bias in non-randomized studies of interventions' (ROBINS-I) tool, or the National Institute for Health Quality Assessment tool for Case Series. Overall strength of evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. DISCUSSION: To-date the outcomes of microsurgical procedures performed on STCSTs to LMICs are largely unknown. Improved education, funding and allocation of resources are needed to support surgeons in LMICs to perform free-tissue transfer. STCSTs provide a vehicle for sustainable collaboration and training. Disseminating microsurgical skills could improve the care received by patients living with reconstructive pathology in LMICs, but this is poorly established. This study sets out a robust protocol for a systematic review designed to critically analyse outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 225613.

Dentoalveolar radiation dose following IMRT in oropharyngeal cancer-An observational study.

OBJECTIVES: This observational study aims to determine individual dental doses in oropharyngeal cancer (OPC) patients managed by intensity modulated radiation treatment (IMRT). MATERIALS AND METHODS: OPC patients treated with IMRT had each tooth individually contoured on post-IMRT CT scans. The mean, maximum and minimum doses were calculated per tooth-based upon patient and tumor demographics (tumor size and nodal status). RESULTS: A total of 160 patients were included in this study. Escalating tumor size and nodal status led to an observed increase in Dmean doses to the dentition on the contralateral tumor side. A significant region in both jaws received >30 Gy in this tumor group. CONCLUSION: Tumor demographics were observed to influence RT doses to the dentition and need to be considered when providing a pre-RT dental assessment. The observed dose of >30 Gy in large spans of the dentition and jaws highlights future risk of dental deterioration and ORN with long term survival.

Adjuvant Alendronic Acid in the Management of Severe Cherubism: A Case Report and Literature Review.

Cherubism is a rare disease of the jaws characterized by bilateral symmetrical painless expansion of the mandible and maxilla. In extreme cases, larger lesions can become exophytic and have profound functional and esthetic implications. Several pharmacologic agents have been trialed in the treatment of cherubism with variable success reported. Bisphosphonates have not been significantly studied in this setting. We present a case where oral alendronic acid was used as an adjuvant treatment after surgical debulking of the maxilla in a 13-year-old boy with a severe case of cherubism.

Barriers to Obtaining Informed Consent on Shortterm Surgical Missions.

Short-term surgical missions (STSMs) enable visiting surgeons to help address inequalities in the provision of surgical care in resource-limited settings. One criticism of STSMs is a failure to obtain informed consent from patients before major surgical interventions. We aim to use collective evidence to establish the barriers to obtaining informed consent on STSMs and in resource-limited settings and suggest practical solutions to overcome them. METHODS: A systematic review was performed using PubMed and Web of Science databases and following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. In addition to the data synthesized from the systematic review, we also include pertinent data from a recent long-term follow-up study in Ethiopia. RESULTS: Of the 72 records screened, 11 studies were included in our review. The most common barrier to obtaining informed consent was a paternalistic approach to medicine and patient education. Other common barriers were a lack of ethics education among surgeons in low-income and middle-income countries, cultural beliefs toward healthcare, and language barriers between the surgeons and patients. Our experience of a decade of reconstructive surgery missions in Ethiopia corroborates this. In a long-term follow-up study of our head-and-neck patients, informed consent was obtained for 85% (n = 68) of patients over a 14-year period. CONCLUSIONS: This study highlights the main barriers to obtaining informed consent on STSMs and in the resource-limited setting. We propose a checklist that incorporates practical solutions to the most common barriers surgeons will experience, aimed to improve the process of informed consent on STSMs.