Effectiveness of transoral robotic surgery for recurrent head and neck cancers: a systematic review protocol.

OBJECTIVE: The objective of this systematic review is to evaluate the best available evidence regarding effectiveness of transoral robotic surgery in patients with recurrent head and neck cancers. INTRODUCTION: Transoral robotic surgery is now an established modality of treatment for primary head and neck cancer, showing good swallowing outcomes and quality of life for patients post-treatment. In patients with recurrent disease, conventional open surgery is often used, which prolongs recovery time and necessitates tissue disruption to gain access to the tumor site. Transoral robotic surgery is an emerging technique in this field as a minimally invasive approach to resection. INCLUSION CRITERIA: The review will include experimental or observational studies that investigated the use of transoral robotic surgery in adults (aged 18 years or older) with recurrent head and neck cancers for oncological, functional, and survival outcomes. METHODS: Three databases will be searched for evidence: PubMed, Embase, and Scopus. Search terms for each database will include transoral robotic surgery, recurrent, salvage , and head and neck cancers . Reference lists of included articles will be searched for further evidence. Critical appraisal will be conducted by 2 independent reviewers using the JBI critical appraisal tools for quantitative studies. Data will be extracted by the same reviewers. Where appropriate, meta-analysis will be conducted for all outcomes. REVIEW REGISTRATION: PROSPERO CRD42023404613.

The effectiveness of fibrin sealants in head and neck surgery: a systematic review protocol.

OBJECTIVE: This review will investigate the effectiveness of fibrin sealants in adult patients who underwent head and neck surgery. INTRODUCTION: Controlling bleeding is important in head and neck surgery. Complications involving nearby vital structures increase the risk of morbidity and mortality. Surgical tissue adhesives are used in addition to other traditional hemostatic methods to reduce surgical site bleeding. Fibrin sealants have shown some success compared with other tissue adhesives, but individual studies have been inconclusive. INCLUSION CRITERIA: We will include studies comparing fibrin sealants with placebo or usual care in patients 18 years or older who have undergone soft tissue surgery of the head and neck with drain placement. Primary outcomes include wound complications and time to surgical drain removal. Secondary outcomes include length of hospital stay, drain volume output, surgical management of postoperative hematoma, rate of blood transfusions, and adverse reactions. METHODS: We will search electronic databases (PubMed, Embase, Cochrane Database of Controlled Trials) for studies published from 1975 onwards. Titles, abstracts, and full-text papers will be assessed against the inclusion criteria by 2 independent reviewers. Study screening and selection will be performed, and critical appraisal conducted using the standardized JBI appraisal tools. Data will be extracted by 2 independent reviewers. Meta-analysis will be conducted for all outcomes where appropriate, with weighted mean differences for continuous data. Risk ratios will be used for dichotomous data. Certainty will be reported using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. REVIEW REGISTRATION: PROSPERO CRD42023412820.

Oncological and functional outcomes of transoral surgery compared with non-surgical management in small-volume oropharyngeal cancer: a systematic review protocol.

OBJECTIVE: The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer. INTRODUCTION: The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy. INCLUSION CRITERIA: The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings. REVIEW REGISTRATION: PROSPERO CRD4202235209.

Disseminated thrombosis of the internal jugular vein, superior ophthalmic vein and cavernous sinus as the primary manifestation of occult malignancy: a case report.

Internal jugular vein (IJV) thrombosis is a life-threatening condition most often associated with local risk factors such as head or neck infection or central venous catheterisation. Underlying malignancy is a rare but important aetiology to consider in patients presenting with spontaneous IJV thrombosis. We describe a case of necrotic cervical lymphadenopathy with thrombosis of the IJVs, cavernous sinuses and superior ophthalmic veins in a patient with metastatic squamous cell carcinoma, which was further complicated by an orbital compartment syndrome. The differential diagnosis of IJV thrombosis includes a range of infective, metastatic and thrombophilic pathologies. This case illustrates that, in the absence of an underlying precipitating factor, spontaneous IJV thrombosis should prompt further systemic investigations. Furthermore, patients with thrombotic events affecting the orbital venous drainage system should be monitored closely for signs of an acute orbital compartment syndrome.

Customised acoustic therapy delivered through a web-based platform-An innovative approach to tinnitus treatment.

OBJECTIVES: Customised acoustic therapy aims to moderate the neural pathways implicated in the pathophysiology of tinnitus. This study aimed to assess the efficacy of customised acoustic therapy administered via a web-based treatment platform. DESIGN: Clinical trial with prospective recruitment. Fifty-eight participants underwent 6 weeks of customised acoustic therapy. SETTING: Treatment was delivered for 2 h each day using a smartphone, tablet or computer. Treatment was integrated into usual daily activities. PARTICIPANTS: Participants with subjective tinnitus were recruited through public and private otolaryngology clinics and electronic and print media. MAIN OUTCOMES MEASURED: FiveQ, a novel 5 question tinnitus questionnaire, was measured at baseline and each week of treatment. Statistical analyses, including Wilcoxon, Mann-Whitney and mixed linear regression, were used to assess treatment efficacy and identify factors associated with treatment response. RESULTS: 39/58 participants (67.2%) had an improvement in symptom severity scores, 4 had no change (6.9%) and 15 had a decline from baseline (25.9%). Mean FiveQ scores improved by 22.9% from 40.8 (SD = 21.4) at baseline to 31.5 (SD = 21.3) following 6 weeks of treatment (p < 0.001). With the exception of the slight tinnitus group, all other groups (from mild to catastrophic) demonstrated a treatment response. Participants with low frequency tinnitus (<2000 Hz) had a significantly greater treatment response (p < 0.001). CONCLUSION: Customised acoustic therapy administered via a web-based platform demonstrated encouraging efficacy. At least mild symptoms at baseline and low frequency tinnitus were associated with a greater treatment response. Customised acoustic therapy offers accessible and efficacious tinnitus treatment, however longer term clinical studies are required to confirm the observed initial benefit is maintained.

Correlation between radiologic and pathologic extranodal extension in HPV-associated oropharyngeal cancer: Systematic review.

Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Unfortunately there is no gold-standard imaging modality for radiological assessment of ENE in HPV+ OPSCC, leading to subjective assessments and complex decision making concerning ENE. A systematic review of diagnostic test accuracy was therefore undertaken, with five databases systemically searched to evaluate the diagnostic performance of an imaging modality for detection of ENE in HPV+ OPSCC. A meta-analysis was conducted on four CT studies using a random-effects model. While a narrative synthesis was provided for the studies using PET/CT and "CT and MRI." Out of 1772 hits, six studies were included in the review. Meta-analysis on four CT studies showed CT had an overall sensitivity of 77% and specificity of 60%. PET/CT had a sensitivity of 37.5% and specificity of 97%. "CT and MRI" had a sensitivity of 62% and specificity of 78%. Further diagnostic studies involving CT, PET/CT and MRI are ultimately required.

Preclinical feasibility of robot-assisted sentinel lymph node biopsy using multi-modality magnetic and fluorescence guidance in the head and neck.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a staging procedure dependent on accurate mapping of draining lymphatics via tracers. Robot-assisted SLNB enables access to multiple neck levels with a single incision and intraoperative fluorescence guidance to the SLN. METHODS: Lymphatic mapping in swine was done using a magnetic tracer and fluorescent dye, injected into the tongue. MRI preoperatively mapped lymphatic spread of the magnetic tracer. Dissection was performed using a da Vinci Xi robot guided by fluorescence-imaging of the dye. RESULTS: Robot-assisted SLNB was successfully performed in all animals (n = 5). A novel MRI protocol differentiated SLNs (n = 6) from lower echelon nodes (n = 11) based on flow progression. Fluorescence imaging provided valuable intraoperative guidance and correlated with magnetic-positive nodes. CONCLUSIONS: This study demonstrates preclinical feasibility of a robot-assisted approach to SLNB using magnetic and fluorescent tracers in the head and neck, enabling both preoperative mapping and intraoperative guidance.

FiveQ: A new easy-to-use validated clinical instrument for tinnitus severity.

OBJECTIVES: Tinnitus is a complex and debilitating phenomenon with potentially significant implications on quality of life. New presentations can be resource and time intensive for clinicians. Validated comprehensive tinnitus questionnaires may lack practical utility in the high-volume clinical setting. Concise, targeted questionnaires may offer an efficient alternative. This study aimed to assess the validity of the FiveQ, a novel five question construct designed to measure tinnitus severity. Convergent validity was assessed through correlating FiveQ against two comprehensive validated questionnaires, the Tinnitus Handicap Questionnaire (THQ) and Tinnitus Handicap Inventory (THI). DESIGN: Cross-sectional study with prospective recruitment. The 117 voluntarily recruited participants completed the FiveQ, THI and THQ questionnaires. Results were comparatively analysed. SETTING: Recruitment was via electronic and print media, audiology clinics and public and private otolaryngology outpatient clinics. Surveys were completed electronically. PARTICIPANTS: Members of the public aged over 18 with subjective tinnitus were invited to participate. MAIN OUTCOME MEASURED: Analyses for establishing the content validity, construct validity, internal consistency, explorary factor analysis, and responsiveness of FiveQ was performed. RESULTS: FiveQ demonstrated a high positive correlation with both the THI (r = 0.773, p < .001) and THQ (r = 0.808, p < .001). Internal consistency for FiveQ reached an acceptable threshold (Cronbach's alpha 0.86). Exploratory factor analysis demonstrated that one latent factor underlies the five items of the FiveQ. FiveQ demonstrated better responsiveness than both the THI and THQ after a 6 week interval repeat measurement. CONCLUSION: FiveQ demonstrated high-positive correlations with existing validated tinnitus questionnaires as well as acceptable internal consistency and factor analysis. The concise construct of FiveQ allows clinicians to efficiently estimate tinnitus severity, target treatment towards dominant symptoms and establish a reliable estimation of treatment response following interventions.

Preclinical evaluation of a mannose-labeled magnetic tracer for enhanced sentinel lymph node retention in the head and neck.

Sentinel lymph node biopsy in cancers of the head and neck offers demonstrated clinical and diagnostic value, but adoption is limited by concerns about the detrimental consequence to survival of false negative results in a highly curable setting. The aim of this study was to demonstrate potential to overcome this via application of a novel mannose-labeled magnetic iron oxide tracer. In a large animal model, preoperative imaging and intraoperative magnetometer detection were used to identify magnetic lymph nodes. Iron quantification mapped the distribution of tracer within lymphatic levels. Over a 4-week test period, uptake of magnetic tracer in lymph nodes increased in a linear-like fashion, with a substantial percentage of accumulated iron (83%) being retained in the sentinel node. This result indicates a high affinity of mannose-labeled particles to the sentinel node, while providing a means for the magnetometer probe to indicate node status based on intraoperative signal.

Accuracy of imaging modalities at detecting extracapsular spread of cervical lymph node metastases in HPV-associated oropharyngeal cancer: a systematic review protocol of diagnostic test accuracy.

OBJECTIVE: The objective of this review is to evaluate the accuracy of different imaging modalities in detecting extracapsular spread (ECS) of cervical lymph node metastases in human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). INTRODUCTION: Extracapsular spread of lymph node metastases is associated with poor prognosis, and its detection in head and neck cancer is crucial for treatment planning. Commonly used imaging modalities to detect ECS in OPSCC include computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasonography. Currently there is no gold standard imaging modality to detect ECS in OPSCC. INCLUSION CRITERIA: This review will consider published studies examining the diagnostic accuracy (including sensitivity and specificity) of an imaging modality used to detect ECS in HPV+ OPSCC. Participants will have a diagnosis of HPV+ OPSCC and suspected diagnosis of ECS of cervical lymph node metastases. The index test will be different imaging modalities used to detect ECS, and the reference test will be histopathology. METHODS: A three-step search strategy will be undertaken to identify relevant studies in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. A standardized critical appraisal tool (QUADAS-2) will be used to assess the methodological quality of the studies. The main outcomes will be sensitivity and specificity measures reported with 95% confidence intervals. Meta-analysis will be conducted using a bivariate model approach after pooling the studies according to imaging modality. Meta-regression will be used to explore heterogeneity. Meta-regression and subgroup analyses will be used to compare studies and imaging modalities. The results will be presented using either paired forest plots, summary receiver operator characteristic curves, or a narrative synthesis. A GRADE Summary of Findings will be provided. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021250626.

Trans-oral robotic surgery for head and neck cancers using the Medrobotics Flex® system: the Adelaide cohort.

Trans-oral robotic surgery for head and neck cancers can be performed using rigid, multi-port robots with linear access but the Medrobotics Flex® system offers an alternative as it is endo-luminal, single-port, and uses flexible instruments. To assess the utility of the Medrobotics Flex® system for head and neck cancer (HNC) resections. A retrospective review of all HNC resections done over a 2.5-year period (Jan 2017-July 2019) at the Memorial Hospital, using the Flex® system. Data collected include patient demographics, tumour site, tumour stage, p16 status, smoking history, surgery performed, histologic margins, complications, overall survival, recurrence, and adjuvant treatments received. There were 49 head and neck cancer cases in total done using the Medrobotics Flex® system. Median age 60 years, with M:F ratio 3.5:1. Outcomes: oropharyngeal cancers (82%), p16 positive (89%), overall survival (94%), local recurrence (6%), and adjuvant treatment (84%). Cancer procedures done included lateral oropharyngectomy (43%), tongue base mucosectomy (27%), tongue base resection (18%), and others (12%) which include a single case each of supraglottic laryngectomy, hypopharyngeal tumour resection, partial pharyngectomy, partial glossectomy, and vocal cord tumour resection. Clear margins were related to tumour T stage and achieved for T1 tonsil cancer (75%), T2 tonsil cancer (70%), T3 tonsil cancer (50%), T1 tongue base cancer (80%), and T2 tongue base cancer (66.7%). Median operating time with neck dissection was 2 h 40 min, whilst median length of hospital stay was 1 day (IQR 1-7 days). Complications included a single case each of secondary haemorrhage (managed conservatively), oro-cervical fistula, wound infection, tongue numbness, and a medical event. There was no primary haemorrhage and no mortality. The Medrobotics Flex® system is a safe and reliable tool for head and neck cancer surgery.

Diurnal Changes in Water Soluble Carbohydrate Components in Leaves and Sucrose Associated TaSUT1 Gene Expression during Grain Development in Wheat.

In plant tissues, sugar levels are determined by the balance between sugar import, export, and sugar synthesis. So far, water soluble carbohydrate (WSC) dynamics have not been investigated in a diurnal context in wheat stems as compared to the dynamics in flag leaves during the terminal phases of grain filling. Here, we filled this research gap and tested the hypothesis that WSC dynamics interlink with gene expression of TaSUT1. The main stems and flag leaves of two genotypes, Westonia and Kauz, were sampled at four hourly intervals over a 24 h period at six developmental stages from heading to 28 DAA (days after anthesis). The total levels of WSC and WSC components were measured, and TaSUT1 gene expression was quantified at 21 DAA. On average, the total WSC and fructan levels in the stems were double those in the flag leaves. In both cultivars, diurnal patterns in the total WSC and sucrose were detected in leaves across all developmental stages, but not for the fructans 6-kestose and bifurcose. However, in stems, diurnal patterns of the total WSC and fructan were only found at anthesis in Kauz. The different levels of WSC and WSC components between Westonia and Kauz are likely associated with leaf chlorophyll levels and fructan degradation, especially 6-kestose degradation. High correlation between levels of TaSUT1 expression and sucrose in leaves indicated that TaSUT1 expression is likely to be influenced by the level of sucrose in leaves, and the combination of high levels of TaSUT1 expression and sucrose in Kauz may contribute to its high grain yield under well-watered conditions.

Transoral robotic narrow field oropharyngectomy for tumours of the parapharyngeal space.

The advent of transoral robotic surgery (TORS) has allowed transoral approaches for parapharyngeal space (PPS) tumours to be re-evaluated. It provides enhanced visualisation and instrument access for appropriate tumours. We describe a specific technique, TORS narrow-field oropharyngectomy, that is ideal for benign PPS tumours which have been violated by intra-oral biopsy or incision and drainage. This allows the contaminated, overlying oropharyngeal mucosa to be resected en-bloc with the PPS tumour, reducing the risk of local recurrence. This technique provides a window into the PPS, improving visualisation of underlying neurovascular structures as well as the tumour. This reduces the risk of tumour spillage and leads to superior vascular access and haemorrhage control. This technique is only applicable to PPS tumours that are appropriate for transoral approaches and is specifically designed for those selected patients that have been placed at risk of seeding or local scarring by intra-oral procedures prior to definitive resection. We present two such cases: a 38-year-old male with a PPS inflammatory cyst and a 66-year-old female with a PSS pre-styloid Schwannoma.

How I do it: transnasal retraction during transoral robotic oropharyngeal resection.

Collapse of the resection plane presents a frustrating problem during transoral robotic resection, in a situation already typified by limited vision and access for instruments. We present a quick and cost-effective retraction technique to effectively mitigate this issue and increase the ease and reliability of robotic oropharyngeal resection. This technique utilises a simple transnasal apparatus to create greater exposure of the resection plane. A Y-suction catheter is inserted into the oropharynx via the nasal cavity. A silk suture is then used to attach it to the oropharyngeal resection specimen. When pulled from the nasal cavity, this apparatus adds a non-intrusive, tremor-free fixation point that pulls the resected specimen along a unique cephalo-posterior vector. This significantly improves access and vision of the desired dissection plane. The entire process takes approximately 1-2 min per side to properly execute. It can be adapted for various pathologies and subsites of the oropharynx. This transnasal technique is a simple, minimally invasive, and inexpensive method for improving wound tension during transoral oropharyngeal resection.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

Prognosis of oral squamous cell carcinoma with perineural invasion: A comparative study of classification types.

OBJECTIVE: To investigate the histological location and extent of perineural invasion (PNI) as prognostic factors. DESIGN: Retrospective review of medical records and histological analysis of 116 patients with oral squamous cell carcinoma (OSCC). SETTING: Two major public tertiary hospitals treating head and neck cancer, Royal Adelaide Hospital and Flinders Medical Centre, in South Australia. PARTICIPANTS: Patients diagnosed with OSCC who underwent primary surgical treatment with curative intent at these two centres from January 1, 2005 through December 31, 2015. MAIN OUTCOME MEASURES: The primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: The presence of PNI as a binary factor alone did not significantly influence the clinical outcomes. Extratumoural (ET) PNI as measured from the tumour edge was associated with worse DFS on multivariate analyses. Multifocal PNI was associated with worse DFS and DSS. DFS in multifocal PNI was worse irrespective of whether adjuvant therapy was administered. CONCLUSIONS: The presence of multifocal and ET PNI in OSCC is associated with poor clinical outcomes. Patients with multifocal PNI were associated with worse DFS even with adjuvant therapy.

Impact of metformin on disease control and survival in patients with head and neck cancer: a retrospective cohort study.

OBJECTIVE: A number of in vitro and clinical studies have suggested potential antineoplastic effects of metformin. The impact of this medication on outcomes in head and neck cancer is less clear. Our aim was to determine the effect of metformin on outcomes within our large cohort of head and neck cancer patients with Type II Diabetes (T2DM). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary Cancer Centre. SUBJECTS AND METHODS: A retrospective review of individuals with head and neck squamous carcinoma (HNSCC) and T2DM between January 2005 and December 2011 at Princess Margaret Cancer Centre was conducted. Medication history was obtained from surveys at initial presentation and electronic medical record review. Using Cox regression analyses, the association between metformin use and local, regional and distant failures was explored. Subgroup analyses were conducted for oral cavity, oropharynx and larynx. RESULTS: A total of 329 HNSCC patients with T2DM were identified, including 195 metformin users and 134 non-metformin users. Patients were well-matched in terms of clinical, pathologic, and treatment factors. No difference in local, regional, or distant failure was observed between diabetic metformin users and diabetic non-metformin users for the entire cohort or within subgroup analysis for subsite. No difference between the two groups was observed for overall survival, recurrence-free survival, and disease-specific survival at 5 years. CONCLUSION: No association between metformin use and oncologic outcomes were observed in this large cohort of HNSCC patients. Multicenter, prospective studies may be needed to verify previous studies identifying a potential anti-neoplastic effect of this medication.

Predictive value of computed tomography in identifying extracapsular spread of cervical lymph node metastases in p16 positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Extracapsular spread (ECS) of lymph node metastases is associated with poor prognosis and is an indication for adjuvant chemoradiotherapy. Accurately identifying ECS using imaging may allow us to recommend primary chemoradiotherapy to avoid trimodality treatment. We investigated the accuracy of staging CT in diagnosing ECS in P16 + oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with pathologically determined cervical nodal metastases from P16 + OPSCC were included. Two blinded radiologists scored images to predict the presence of ECS in comparison to histopathology. RESULTS: Eighty patients with a total of 91 specimens were evaluated. Pathologic ECS was identified in 53.8% of the patients. Sensitivity and specificity of CT for the two observers were 56.5% and 60.9%, and 73.3% and 66.7%, respectively. The presence of perinodal stranding was found to be significantly associated with pathological ECS. CONCLUSION: Computed tomography displays consistently high specificity, which may be used to rule out the presence of extracapsular spread in cervical nodal metastases of P16 + oropharyngeal squamous cell carcinoma.