The molecular characteristics of recurrent/metastatic HPV-positive head and neck squamous cell carcinoma: A systematic review of the literature.

OBJECTIVES: About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers. DESIGN: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria. RESULTS AND CONCLUSIONS: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.

A study of variation in therapeutic approach to low-risk differentiated thyroid cancer in the UK.

BACKGROUND: The British Thyroid Association and American Thyroid Association guideline definitions for low-risk differentiated thyroid cancers are susceptible to differing interpretations, resulting in different clinical management in the UK. OBJECTIVE: To explore the national effect of these guidelines on the management of low-risk differentiated thyroid cancers. METHODS: Anonymised questionnaires were sent to multidisciplinary teams performing thyroidectomies in the UK. Risk factors that multidisciplinary teams considered important when managing low-risk differentiated thyroid cancers were established. RESULTS: Most surgeons (71 out of 75; 94.7 per cent) confirmed they were core multidisciplinary team members. More than 80 per cent of respondents performed at least 30 hemi- and/or total thyroidectomies per annum. A majority of multidisciplinary teams (50 out of 75; 66.7 per cent) followed British Thyroid Association guidelines. Risk factors considered important when managing low-risk differentiated thyroid cancers included: type of tumour histology findings (87.8 per cent), tumour size of greater than 4 cm (86.5 per cent), tumour stage T3b (85.1 per cent) and central neck node involvement (85.1 per cent). Extent of thyroid surgery (e.g. hemi- or total thyroidectomy) was highly variable for low-risk differentiated thyroid cancers. CONCLUSION: Management of low-risk differentiated thyroid cancers is highly variable, leading to a heterogeneous patient experience.

The impact of surgical set-up of endoscopic two surgeon four hand anterior skull base surgeries on surgeons' ergonomics.

BACKGROUND: The impact of different surgical set-ups of endoscopic two surgeon four hand anterior skull base surgeries on surgeons' ergonomics remain unclear. This study aims to explore the effect of surgeon, patient and surgical screen positioning on surgeons' ergonomics using the Rapid Entire Body Assessment (REBA) tool. METHODS: A total of 20 different surgical positions of anterior skull base surgery were simulated and the ergonomic impact on surgeons' neck, truck, leg and wrist were measured using the validated Rapid Entire Body Assessment (REBA) tool. To investigate the ergonomic effect of different surgical setups, the operating surgeon, assisting surgeon, patient head, camera and screen positions were positioned differently in each surgical position. RESULTS: The lowest REBA Score recorded is 3 whereas the highest score is 8. The REBA scores for the majority of positions are 3 highlighting that these positions are ergonomically favorable. Position 12 is the least ergonomically favorable position with a total REBA score of 19. In this position, operating surgeon is positioned to the right of the patient, assisting surgeon to the left of patient, patient head in central position with camera held by operating surgeon and one screen is placed to the right of patient. Positions 13 and 17 are the most ergonomically favorable positions with a total REBA score of 12. In these positions, the patient's head is positioned to the center, two screens were utilized, and the surgeons were positioned on either side of the patient. The utilization of 2 screens with a central patient head position with the surgeons placed on either side of the patient contribute towards a more ergonomically state in these positions. CONCLUSIONS: Certain positional behaviors are better at reducing musculoskeletal injury risk when compared to other. Positions with two screens and central head positions are more favourable ergonomically and surgeons should consider this set-up to reduce musculoskeletal injuries during anterior skull base surgery.

Active surveillance for PTMC warranted for the UK population?

BACKGROUND: The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1 cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the United Kingdom's (UK's) approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. OBJECTIVE: This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. DESIGN, PARTICIPANTS, AND OUTCOME MEASURES: Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. RESULTS: From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging, and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would, therefore, be realistic candidates for active surveillance. CONCLUSION: Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programmes to deal with this minority of patients, focus should be maintained on minimising detection of these low-risk cases.

Patient and physician positioning during anterior skull base surgery impacts physician ergonomics.

BACKGROUND: The effects of anterior skull base surgery on surgeon's ergonomics remain unclear and this study explores the impact of patient, surgeon and screen positioning on surgeon's ergonomics during anterior skull base surgery using the Rapid Upper Limb Assessment (RULA) tool. METHOD: A total of 20 different surgical positions involving the operating surgeon, assisting surgeon, patient head position, camera position and screen position/number were simulated. For each position, the ergonomic effects on the upper limb, neck, trunk and lower limb of surgeons were analysed using the Rapid Upper Limb Assessment (RULA) tool. RESULTS: The lowest RULA score is 2 and the maximum score is 6. The majority of scores ranged from 2 to 3 suggesting the majority of positions have acceptable postures. The average RULA score of the right side of operating surgeon was 2.8 versus 2.95 on the left-side (p = 0.297). For the assisting surgeon, the average RULA score of the right side was 3.65 versus 3.25 for the left side (p = 0.053). The average combined (left and right) RULA score for the operating surgeon was 5.76 versus 6.9 for the assisting surgeon (p < 0.001). Position 17 (operating surgeon to the right of patient, assisting surgeon to the left of patient, central patient head position and two screens) is the most ergonomically favourable position. Position 2 (operating and assisting surgeon to the right of patient, patient head position to the right and one screen position to the left of patient) is the least favourable position. CONCLUSION: This simulation raises awareness of risk of musculoskeletal injury in anterior skull base surgery and highlights that certain positional behaviours are better for reducing injury risk than others. Two screens should be considered when performing a two-surgeon, four-hand anterior skull base surgery and surgeons should consider applying this to their own ergonomic environment in theatre.

Outpatient (same-day discharge) versus inpatient parotidectomy: A systematic review and meta-analysis.

BACKGROUND: Parotidectomy is often performed as an inpatient procedure largely due to drain insertion; however, outpatient parotidectomy has increasingly become an attractive alternative for its shorter hospital stays and greater efficiency in cost-effectiveness. OBJECTIVE OF REVIEW: To assess the safety and feasibility of outpatient (or same-day discharge) parotidectomy compared with inpatient parotidectomy. TYPE OF REVIEW: Systematic review of the literature and meta-analysis, in accordance with the PRISMA guidelines. METHODS: Pubmed/Medline, Embase, CINAHL, Google Scholar, Web of Science, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published in English between 01/01/1990 and 05/10/2019. The Newcastle-Ottawa Scale was used for quality assessment and Review Manager 5.3 for meta-analyses. MAIN OUTCOME MEASURES: Primary outcomes assessed were postoperative complications including bleeding/haematoma, surgical site infection, seroma and facial weakness. Secondary outcome was readmission rate. RESULTS: Out of 445 studies identified, 6 were selected for systematic review. The overall quality of evidence was moderate. A total of 3664 patients were included (1646 in the outpatient group and 2018 in the inpatient group). Comparing the outpatient with inpatient cohorts, there were lower complications in outpatient groups though not statistically significant for haematoma (OR = 0.45; 95% CI = 0.11-1.92; P = .28), surgical site infection (OR = 0.88; 95% CI = 0.46-1.69; P = .70), seroma (0.79; 95% CI = 0.21-3.03; P = .74), facial nerve weakness (OR 0.39; 95% CI = 0.14-1.08; P = .07) and hospital readmission (OR 0.58; 95% CI = 0.33-1.04; P = .07). CONCLUSIONS: Outpatient parotidectomy appears to be safe and compares favourably to inpatient procedure in postoperative complication and readmission rates.

Exploration of temporal bone anatomy using mixed reality (HoloLens): development of a mixed reality anatomy teaching resource prototype.

Mixed reality (MR), a technology which supplements the real world with virtual objects, is increasingly becoming available as a teaching tool in medical education. The Microsoft HoloLens device allows operators to experience MR using a head-mounted device without interfering with their physical reality, stimulating a realistic learning experience using virtual objects. This project aimed to develop a MR anatomy teaching application with HoloLens for exploring the anatomy of the temporal bone. The educational application was developed from a multidisciplinary collaboration between undergraduate and postgraduate students across several academic disciplines with Medtronic, a medical technology company. 3D anatomical models were built using ZBrush and Blender, while the HoloLens1 application was developed using Windows 10, Visual Studio 2017, Unity and Mixed Reality Toolkit (MRTK). Modules developed within the application included a basic HoloLens tutorial, a virtual temporal bone with surgical anatomy landmarks and free drilling of the temporal bone. The basic tutorial allows the operator to adapt to the MR environment prior to exploring the anatomical landmarks of the 3D temporal bone. The free drilling of the temporal bone using vertex displacement and texture stretching replicates a real-time bone drilling experience and allows the operator to explore the anatomical relationship between different otological structures.

E-cigarettes and head and neck cancers: A systematic review of the current literature.

BACKGROUND: Cigarette smoking is a well-established risk factor for head and neck (HN) cancers. Use of electronic cigarettes (e-cigarettes) is gaining popularity, being advertised as benign alternatives to tobacco. A wide variety of potentially harmful chemical components with variable quantity have been identified in e-liquids and aerosols of e-cigarettes. However, use of e-cigarettes remains controversial due to conflicting evidence. OBJECTIVES: We aimed to assess the association between e-cigarettes and HN cancers. We conducted a systematic review to evaluate the literature for evidence on carcinogenic effects of e-cigarettes in the pathogenesis of HN cancers. TYPE OF REVIEW: Qualitative systematic review. SEARCH STRATEGY: A PubMed/MEDLINE, Cochrane, CINAHL Plus, Trip Medical Database and Web of Science search was done for studies on e-cigarettes and HN cancer. EVALUATION METHOD: Abstract review of all articles, full article revision of included studies, data extraction and quality assessment were performed by two independent assessors. RESULTS: The literature search resulted in the identification of 359 articles. Eighteen articles were selected for inclusion into the systematic review. The majority were laboratory-based studies, followed by several cohort and case studies, representing low-level evidence. A few reports suggested DNA damage following exposure to e-cigarettes potentially due to increased oxidative stress. Flavoured e-liquids appear to be more harmful. There is variable evidence from clinical studies. CONCLUSIONS: Our review outlines potential dangers associated with the use of e-cigarettes and their role in HN cancers. More longitudinal and controlled studies are needed to assess the possible link between e-cigarettes and HN cancers.

Pathogenicity and Penetrance of Germline SDHA Variants in Pheochromocytoma and Paraganglioma (PPGL).

Germline SDHA mutations are reported in a minority of pheochromocytoma/paraganglioma (PPGL) cases but are associated with an increased risk of malignancy, leading some to advocate cascade genetic testing and surveillance screening of "at-risk" first-degree relatives. However, such approaches rely on accurate estimates of variant pathogenicity and disease penetrance, which may have been subject to ascertainment and reporting biases, although the recent provision of large population-based DNA sequence data sets may provide a potentially unbiased resource to aid variant interpretation. Thus, the aim of the current study was to evaluate the pathogenicity and penetrance of SDHA variants reported in literature-based PPGL cases by comparing their frequency to those occurring in the Genome Aggregation Database (GnomAD) data set, which provides high-quality DNA sequence data on 138,632 individuals. In total, 39 different missense or loss-of-function (LOF) SDHA variants were identified in 95 PPGL index cases. Notably, many of the PPGL-associated SDHA alleles were observed at an unexpectedly high frequency in the GnomAD cohort, with ~1% and ~0.1% of the background population harboring a rare missense or LOF variant, respectively. Although the pathogenicity of several SDHA alleles was supported by significant enrichment in PPGL cases relative to GnomAD controls, calculations of disease penetrance based on allele frequencies in the respective cohorts resulted in much lower estimates than previously reported, ranging from 0.1% to 4.9%. Thus, although this study provides support for the etiological role of SDHA in PPGL formation, it suggests that most variant carriers will not manifest PPGLs and are unlikely to benefit from periodic surveillance screening.