Circulating tumour cells predict recurrences and survival in head and neck squamous cell carcinoma patients.

Patients with head and neck squamous cell carcinoma (HNSCC) are at a high risk of developing recurrence and secondary cancers. This study evaluates the prognostic and surveillance utilities of circulating tumour cells (CTCs) in HNSCC. A total of 154 HNSCC patients were recruited and followed up for 4.5 years. Blood samples were collected at baseline and follow-up. CTCs were isolated using a spiral microfluid device. Recurrence and death due to cancer were assessed during the follow-up period. In patients with HNSCC, the presence of CTCs at baseline was a predictor of recurrence (OR = 8.40, p < 0.0001) and death (OR= ∞, p < 0.0001). Patients with CTCs at baseline had poor survival outcomes (p < 0.0001). Additionally, our study found that patients with CTCs in a follow-up appointment were 2.5 times more likely to experience recurrence or death from HNSCC (p < 0.05) prior to their next clinical visit. Our study highlights the prognostic and monitoring utilities of CTCs' in HNSCC patients. Early identification of CTCs facilitates precise risk assessment, guiding treatment choices and ultimately enhancing patient outcomes.

A novel saliva-based miRNA profile to diagnose and predict oral cancer.

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD). The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n = 50), OPMD (n = 52), and controls (n = 60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p, miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was: area under curve (AUC): 0.954, sensitivity: 86%, specificity: 90%, positive predictive value (PPV): 87.8% and negative predictive value (NPV): 88.5% whereas between OC and OPMD was: AUC: 0.911, sensitivity: 90%, specificity: 82.7%, PPV: 74.2% and NPV: 89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC, revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Nutritional management of chyle leak after head and neck surgery: a systematic review and proposed protocol for management.

PURPOSE: Chyle leaks are a rare complication of neck surgery causing local damage, impairing healing and compromising free flaps. High output leaks can result in electrolyte imbalances and malnutrition. Nutritional management such as restricting the absorption of triglycerides is believed to reduce chyle, allowing spontaneous resolution of a leak. Dietary preparations and management can aid in reducing chyle production. There are no clear guidelines to aid nutritional decision-making in this complex scenario. METHODS: A systematic review of the literature was carried out to identify studies evaluating nutritional management of chyle leaks in patients after neck dissections. RESULTS: Ten studies were identified evaluating the role of nutritional therapy in the management of patients with chyle leaks after neck dissections. The level of evidence was low. Several studies identified that low volume leaks (defined as < 1000 mls per day) often resolved by dietary management and other conservative measures. High volume leaks rarely resolved with conservative measures alone. Parenteral nutrition had an established role in this context. CONCLUSIONS: There is limited evidence to guide dietary restriction and introduction of oral diet in patients with chyle leak after major head and neck surgery. Based on available evidence, local guidelines for the nutritional management of patients identified with a chyle leak were produced and adopted by the Trust and the head and neck MDT. A national database for voluntary contribution of prospective data would help to generate better quality management protocols.

Impact of dental state and surgical factors on postoperative neck infection in oral cancer patients.

Postoperative neck infection (PONI) is a known complication of neck dissection. In this study we explored the impact of dental status on the development of PONI, using orthopantomograms to assess edentulism, periodontal health, and caries status. Retrospective analysis was performed for all new oral cancer patients who had neck dissection between January 2008 and January 2020 in a tertiary head and neck centre. PONI risk factors assessed included patient characteristics, dental status, tumour, and surgical factors. Development of PONI was the primary outcome. Edentulous patients had lower risk of PONI (OR 0.06, p = 0.026) compared to those with 21 or more teeth. Periodontitis and dental caries were not statistically significant. Current smokers (OR 2.09, p = 0.044) and free flap reconstruction (OR 5.41, p < 0.001) were also significant predictors for development of PONI. This study highlights the presence of teeth as a potential source of infection post neck dissection and that orthopantomogram assessment may be inadequate to identify at risk patients. Future studies are required on direct clinical assessment of dentition to evaluate the impact of dental optimisation in prevention of PONI.

3D printing for bone regeneration: challenges and opportunities for achieving predictability.

3D printing offers attractive opportunities for large-volume bone regeneration in the oro-dental and craniofacial regions. This is enabled by the development of CAD-CAM technologies that support the design and manufacturing of anatomically accurate meshes and scaffolds. This review describes the main 3D-printing technologies utilized for the fabrication of these patient-matched devices, and reports on their pre-clinical and clinical performance including the occurrence of complications for vertical bone augmentation and craniofacial applications. Furthermore, the regulatory pathway for approval of these devices is discussed, highlighting the main hurdles and obstacles. Finally, the review elaborates on a variety of strategies for increasing bone regeneration capacity and explores the future of 4D bioprinting and biodegradable metal 3D printing.

Rigid versus non-rigid fixation for bilateral mandibular angle fractures: a retrospective multicentre review.

BACKGROUND: Fractures involving the bilateral mandibular angle are an uncommon occurrence with limited evidence to inform the ideal fixation requirements for adequate treatment. The aim of this study was to evaluate the outcomes of managing bilateral mandibular angle fractures and determine if rigid fixation on one side improves outcomes compared to bilateral non-rigid fixation. METHODS: Patients with isolated bilateral mandibular angle fractures surgically treated at the Royal Brisbane and Women's Hospital, Princess Alexandra Hospital, Gold Coast University Hospital and Townsville University Hospital between January 1, 2010 and December 31, 2022 were retrospectively identified. Data collected included patient demographics, mechanism of injury, fixation scheme, postoperative occlusion and the occurrence of postoperative complications and subsequent management. RESULTS: Eighty-four patients met the inclusion criteria. Fifty-two patients had non-rigid fixation applied to both fractures, and thirty-two had rigid fixation placed on at least one side. All cases proceeded to union. There was no statistically significant difference between the groups for occlusal outcomes, wound dehiscence, infection or plate or screw loosening. CONCLUSION: Our results suggest that bilateral non-rigid fixation can be used to treat bilateral mandibular angle fractures in the appropriate clinical context.

Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.

Tumour Necrosis Factor Alpha (TNF-α) and Oral Squamous Cell Carcinoma.

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.

An objective analysis of composite free flap donor site morbidity in head and neck surgery: Prospective series.

BACKGROUND: A poor evidence basis exists regarding the objective donor site morbidity associated with osseous free flap harvest. This study prospectively assessed the objective donor site morbidity associated with osseous free flap harvest for the fibula, scapula, and iliac crest (DCIA) donor sites. METHODS: A single-site, prospective cohort clinical research study was conducted. Sixty-four patients were recruited between 2017 and 2021. Patients were assessed using a donor site specific assessment tool pre-operatively, and again >12 months post-operatively. RESULTS: There was a significant reduction post-operatively in assessment tool scores compared to the pre-operative period for the fibula, scapula and DCIA. Females were more likely to report a greater reduction in Harris Hip Score post-operatively compared to males. CONCLUSIONS: The fibula, scapula, and DCIA donor sites are associated with reduced objective function post-operatively compared to patient's pre-operative baseline. The implications are least pronounced for the fibula.

Effectiveness of prophylactic tranexamic acid versus placebo or no intervention for reducing blood loss in healthy patients undergoing orthognathic surgery: a systematic review protocol.

OBJECTIVE: The objective of this review is to evaluate the effectiveness of perioperative prophylactic tranexamic acid for reducing blood loss in orthognathic surgery in healthy patients. INTRODUCTION: Orthognathic surgery can cause significant hemorrhage, which requires postoperative blood transfusions. The most widely studied pharmaceutical adjunct for reducing blood loss is tranexamic acid, a synthetic amino acid that reversibly inhibits plasminogen activation. It is widely used and validated in other surgical procedures to limit blood loss; however, it is not a gold standard in orthognathic surgery. INCLUSION CRITERIA: We will include clinical trials comparing tranexamic acid to appropriate controls. The primary outcomes are intraoperative blood loss, change in hematocrit/hemoglobin level, and need for blood transfusion. Secondary outcomes include operating time, length of hospital stay, and adverse reactions. Studies of patients with pre-existing coagulopathies and those undergoing only minor orthognathic surgery (eg, genioplasty) will be excluded. METHODS: We will search 3 electronic databases (PubMed, Embase, and Cochrane Library) from database inception. Titles, abstracts, and full-text papers will be assessed against the inclusion criteria by 2 independent reviewers. Risk of bias will be assessed using the Cochrane Risk of Bias 2.0 tool. Data will be extracted by 2 independent reviewers. Meta-analysis will be conducted for all outcomes where appropriate, with weighted mean differences used for intraoperative blood loss, changes in hematocrit/hemoglobin levels, operation time, and length of stay; and risk ratio for transfusion rates and adverse outcomes. Certainty of the evidence will be presented using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022314403.

Does neoadjuvant chemotherapy provide a survival benefit in maxillofacial osteosarcoma: A systematic review and pooled analysis.

Maxillofacial osteosarcoma (MFOS) is a rare disease that presents and behaves differently to the more commonly seen osteosarcoma (OS) of long bones. Neoadjuvant chemotherapy (neoCTx) has been shown to increase survival in OS of long bones, however it is contentious whether it has the same benefit when treating MFOS. The aim of this review was to determine whether neoCTx has a survival benefit for MFOS. Pubmed/Medline, EMBASE and CINAHL databases were searched. Of the 264 studies identified 18 were included reporting on the effect of neoCTx on survival. Individual data of 222 patients was pooled, and survival was estimated using Kaplan-Meier method and variables were assessed using Cox regression. NeoCTx had no significant effect on disease specific survival (p = 0.28). Margin status, age and grade of tumour had a significant effect on survival. This study did not find a consistent survival benefit for neoCTx over surgery as the primary treatment modality in the management of osteosarcomas of the head and neck.

Association of low skeletal muscle mass and systemic inflammation with surgical complications and survival after microvascular flap reconstruction in patients with head and neck cancer.

BACKGROUND: Skeletal muscle mass (SMM) and chronic inflammation are associated with postoperative complications and survival. METHODS: Patients with head and neck cancer (HNC) undergoing microvascular free flap reconstruction were included. SMM and neutrophil-to-lymphocyte ratio (NLR) were measured and their association with treatment outcomes analyzed. RESULTS: Five hundred and fifty-four patients were included. Predictors for complications were elevated NLR in all flaps (OR 1.5), low SMM in radial forearm flap (OR 2.0), and elevated NLR combined with low SMM in fibula flap surgery (OR 4.3). Patients with solely elevated NLR were at risk for flap-related complications (OR 3.0), severe complications (OR 2.2), and when combined with low SMM for increased length of hospital stays (LOS) (+3.9 days). In early-stage HNC, low SMM (HR 2.3), and combined elevated NLR with low SMM (HR 2.6) were prognostics for decreased overall survival. CONCLUSIONS: SMM and NLR are predictive for poor outcomes in patients with HNC undergoing microvascular reconstruction.

An evaluation of the clinical utility of C-reactive protein and antibiotic use in patients undergoing major head and neck reconstructive surgery with outcome assessment.

PURPOSE: This ambispective observational study aims to evaluate the local utility of peri-operative CRP testing and prophylactic antibiotics in relation to post-operative complications in patients who have undergone major head and neck oncological reconstructive surgery. RESULTS: A total of 79 patients were identified for inclusion; CRP testing was undertaken within the first 3 days postoperatively in 78/79 cases. Results demonstrated no benefit of extended prophylactic antibiotic use in reducing post-operative infection. Forty-two post-operative complications arose. In the prospective arm, CRP did not influence the decision to commence antibiotic therapy for any of the surgical site infections. Age, diabetes, smoking, or high body mass index (BMI) did not appear to affect the incidence of postoperative infection (p > 0.05). There is no evidence that more than 24 h of antibiotic prophylaxis is indicated for patients undergoing head and neck reconstructive surgery. CONCLUSION: Everyone who is involved in peri-operative patient care should be educated regarding the appropriate use of CRP testing, with the implementation of protocols required to standardize CRP testing and prophylactic antibiotic prescription.

Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS (p = 0.86) or OS (p = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS (p = 0.01) but not OS (p = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT.

Novel In-House Design for Fibula Cutting Guide With Detachable Connecting Arm for Head and Neck Reconstruction.

The use of in-house 3D planning and manufacture has become more common in high-volume head and neck reconstructive centers worldwide. Various fibula cutting guides have been designed to allow for accurate and predictable head and neck reconstruction. In this paper, we describe the design, manufacture, and operative technique for use of a novel fibula cutting guide with detachable connecting arms. This straightforward design produces a guide that is less bulky, provides better access for safe osteotomies, and is versatile and adjustable to minimize bone removal between segments.

Clear Cell Odontogenic Carcinoma: First Report of Novel EWSR1-CREM Fusion Gene in Case of Long-Term Misdiagnosis.

Clear Cell odontogenic Carcinomas (CCOC) are rare, aggressive malignant odontogenic tumours which are often misdiagnosed as benign odontogenic tumours due to the non-specific histologic appearance, and benign early clinical presentation. However, due to their propensity to metastasize, the best outcomes are experienced with they are diagnosed early and treated aggressively. In this paper, we present a case of a CCOC misdiagnosed as a clear cell calcifying epithelial odontogenic tumour which was only found to be a CCOC after cervical node metastasis. The original diagnosis was questioned and confirmed to be a CCOC by identification of the chromosomal translocation EWSR1 on fluorescence in situ hybridization. This has recently been described in CCOC and a wide variety of other mesenchymal and epithelial neoplasms. Previous reports have demonstrated EWSR1-ATF1 and EWSR1-CREB1 fusions in CCOC. Next generation sequencing of this case demonstrated the EWSR1-CREM fusion gene which has not been previously reported for CCOC. CREM fusion proteins have only recently been found in several tumour types including the closely associated hyalinizing clear cell carcinoma of salivary glands. This is discussed in this paper, and the role of the discovery of the CREM fusion protein in CCOC adds to your understating of the role of CREM in oncogenesis, and the possible link between CCOCs and hyalinizing clear cell carcinomas.

Tumefactive fibroinflammatory lesion of the maxilla: Successful resection and microvascular reconstruction after failed medical therapy.

Tumefactive fibroinflammatory lesions (TFILs) of the head and neck are rare and benign but locally aggressive lesions. The etiology and pathogenesis of these lesions are unknown. Medical management is regarded the first line of treatment. Surgical management has been rarely reported for head and neck lesions. A 51-year-old female presented with a 6-month history of left facial swelling and pain that subsequently developed into progressive inframalar hollowing and asymmetry. Biopsies confirmed tumefactive fibroinflammatory lesion of the maxilla. Initial treatment with high-dose steroids led to temporary partial involution; however, symptoms progressed. Cyclophosphamide and then rituximab were commenced, with minimal response. Imaging showed progression toward the infratemporal fossa. The patient subsequently underwent a resection and microvascular free flap reconstruction This patient had a successful surgical outcome and resolution of serum inflammatory markers with no evidence of recurrence after 18-month follow-up. A multidisciplinary approach is crucial to ensure a pragmatic patient-specific management plan is developed. Surgical resection and reconstruction can be successful in these lesions and should be considered if medical therapy has failed.

Follow up imaging of oral, oropharyngeal and hypopharyngeal cancer patients: Comparison of PET-CT and MRI post treatment.

There is currently no consensus as to the ideal timing, frequency and modality of imaging for follow up of head and neck cancer patients. The aim of this study was to analyze the diagnostic accuracy of PET-CT versus MRI, and imaging at 3 versus 6 months for follow up of head and neck cancer patients treated with curative intent with no clinical signs of treatment failure. MATERIALS AND METHODS: A retrospective study was performed for all head and neck cancers treated with curative intent at the Royal Derby Hospital. Data collected included demographic information, site of primary cancer, staging, treatment provided, type of follow up imaging performed and results of follow up imaging. Inclusion in the study was for oral, oropharyngeal and hypopharyngeal cancers treated with curative intent, asymptomatic patients, those who have had follow up imaging within 6 months of treatment, and those followed up for at least 2.5 years since treatment. RESULTS: A total of 140 patients were included in the study. 25% of patients had evidence of recurrent/metastatic disease on imaging, 60% of which were identified within 6 months post treatment. The majority (60%) of failures were due to distant metastases. The sensitivity and specificity of both MRI and PET-CT was higher at 6 months post-treatment compared to 3 months post-treatment. Overall the sensitivity and specificity for PET-CT and MRI within 3-6 months post treatment were 94.7% and 83.5% and 60% and 85.7% respectively for identifying treatment failure. CONCLUSION: Follow up Imaging at 6 months post treatment is more likely to accurately identify treatment failures with fewer false positives than imaging at 3 months. PET-CT is preferable to MRI for identifying post treatment locoregional and distant treatment failure.

Rehabilitation post maxillary and mandibular reconstruction: Current status and future approaches.

Rehabilitation post reconstruction in head and neck cancer surgery is a vital component to improving quality of life. In this paper we discuss the current approaches to reconstruction of the maxilla and mandible and how they pertain to rehabilitation. There is a detailed discussion of dental rehabilitative challenges with different composite flaps and ways to solve those challenges. We conclude with a discussion about future approaches to reconstruction and how they will impact on improving rehabilitative outcomes and ultimately improve the quality of life of our patients.