Prognostic biomarkers for malignant progression of oral epithelial dysplasia: an updated systematic review and meta-analysis.

Oral epithelial dysplasia (OED) is a premalignant condition that carries an appreciable risk of malignant progression. The current grading system for severity, as defined by the World Health Organization, is a valuable clinical tool, but further work is required to improve the accuracy of predicting OED malignant progression. This systematic review aimed to assess progress in prognostic biomarker discovery in OED over the past 16 years. The primary objective was to update the latest evidence on prognostic biomarkers that may predict malignant progression of OED, with strict inclusion criteria of studies with a longitudinal design and long-term follow-up data to enhance the robustness and translational clinical potential of the findings. Of 2829 studies identified through the searching of five databases, 20 met our inclusion criteria. These studies investigated a total of 32 biomarkers, 20 of which demonstrated significant potential to predict malignant progression of OED. Meta-analysis demonstrated the significant prognostic value of four biomarkers: podoplanin, EGFR expression, p16 methylation, and DNA aneuploidy. Our review has identified 20 reported biomarkers with prognostic potential to predict malignant progression in OED, but their translation into clinical practice remains elusive. Further research is required, and this should focus on validating the promising biomarkers identified in large cohort studies, with adherence to standardised reporting guidelines.

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.

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.

Admission patterns and outcomes of postoperative oral cavity and oropharyngeal cancer patients admitted to critical care in the UK: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

Surgery for head and neck malignancy may be complex with postoperative admission to critical care units (CCUs) often required. There are, however, increasing demands on this resource. We examined a national intensive care database to assess patterns of admission and outcomes for patients following surgery for malignancies of the oral cavity and oropharynx. An analysis was performed of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme database. Data were extracted on case mix and outcomes for patients coded as 'malignant neoplasm of the oropharynx requiring surgery' admitted to critical care between 2010 and 2019. Data included admission numbers, demographics, comorbidities, physiology scores, and outcomes including length of stay and mortality. There were 9,843 admissions for patients with malignancies of the oral cavity and oropharynx from 156 CCUs over the ten-year period. Admissions increased from 486 in 2010 to 1,381 in 2019. These admissions accounted for 0.42% of overall admissions in 2010 and 0.78% in 2019. The median age of patients was 63 years and 63.5% were male. The median length of stay in critical care was 38 hours (Interquartile range (IQR) 20.4-64.3 hours). The median length of total hospital stay was 15 days (IQR 10-23 days). Mortality in critical care was low (0.7%). Admissions to CCUs following surgery for malignancies of the oral cavity and oropharynx have increased over the last decade but remain low overall. With increasing demand for this resource, ongoing monitoring of utilisation is important.

Admission patterns and outcomes of patients admitted to critical care in the UK with surgically treated facial infection: an analysis of the Intensive Care National Audit and Research Centre Case Mix Programme database.

Facial infections are common and can occasionally be severe. A small number of patients may develop severe sepsis or airway compromise requiring critical care admission. We examined a national intensive care database to assess patterns of admission and outcomes for patients in this cohort. An analysis was performed of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme database. Data were extracted on case mix and outcomes for patients coded as 'mandible, facial bones, dental, and salivary infection' admitted to critical care between 2010 and 2019. Data included admission numbers, demographics, comorbidities, physiology scores, and outcomes including length of stay and mortality. There were 2820 admissions for patients with facial infections from 212 CCUs over the ten-year period. Admissions increased from 194 in 2010 to 368 in 2019. These admissions accounted for 0.16% of overall admissions in 2010 and 0.21% in 2019, a statistically significant increase in the rate of admissions, p < 0.001. The median age of patients was 48 years and 62.7% were male. Sepsis was present in 77.6% of patients. The median length of stay in critical care was 49 hours (IQR 23.2, 100.3 hours). The median total hospital stay was 7 days (IQR 4, 16 days). The rate of admissions to CCUs for facial infection remains low overall but has significantly increased over the last decade. With increasing demand for this resource ongoing monitoring of utilisation is important.

Septic Arthritis of the Temporomandibular Joint with Intracranial Extension: A Case Report.

Septic arthritis of the temporomandibular joint (TMJ) is rare with few cases reported in the literature. We present a case of septic arthritis of the left TMJ in an 18-year-old man who was initially referred as a suspected TMJ dislocation. He had a 3-day history of pain, trismus and malocclusion with left preauricular swelling and became clinically septic with a positive blood culture containing Fusobacterium necrophorum. Computed tomography revealed left TMJ effusion. A later scan showed evidence of a temporal space collection and development of an intracranial extension in the left middle cranial fossa. The patient underwent needle arthrocentesis and drainage, followed by six weeks of antibiotic therapy following advice from neurosurgery and microbiology. Further imaging revealed resolution of the collection. Few cases have been reported of this unusual diagnosis, and this case demonstrates the importance of close multidisciplinary input in forming an accurate diagnosis and managing appropriately.

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.

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.

Tracheal Stenosis after Tracheostomy.

INTRODUCTION: Tracheal stenosis is a late and usually non-life threatening complication of surgical and percutaneous tracheostomies (PDT) as well as delayed endotracheal extubation. METHODS: We undertook a retrospective review of all patients who underwent a surgical tracheostomy over a 10 year period. Patients were included in the study if they had CT or MRI imaging of the tracheostomy site both pre-operatively and six or more weeks post operatively. Patients whose imaging was not available were excluded (n = 3) as were those patients who still had a tracheostomy in situ (n = 8). In total 91 patients were included in the study. In the same period 1170 surgical tracheostomies were performed by the maxillofacial surgeons. The images were analysed by a radiologist and the degree of stenosis reported. RESULTS: All 91 patients underwent a tracheostomy with a window. 83 patients did not demonstrate any stenosis. Looking at the remaining 8 patients with stenosis: 6 patients had stenosis of less than 25%, 1 patient had stenosis between 25-50% and 1 patient had stenosis greater than 50%. Both patients with stenosis greater than 25% had more than one surgical tracheostomy. CONCULSION: We have shown that the risk of stenosis is 8.8%, lower than often quoted in literature, and when it occurs it is likely to be symptomatic only in severe stenosis. Our main risk of stenosis was repeat surgical tracheostomies which also seems to be linked to a greater degree of stenosis.

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.

The vessel-depleted neck in head and neck microvascular reconstruction: extreme solutions for extreme situations.

PURPOSE OF REVIEW: The vessel-depleted neck is the ultimate challenge for the head and neck reconstructive surgeon. In patients who have had previous neck dissections or radiotherapy, the arterial and venous options for future reconstruction can be very limited, and it is important for the surgeon to consider alternative options for vessels. RECENT FINDINGS: Appropriate preoperative planning is crucial in these patients with a thorough history including previous operation notes, details of previous treatments, and previously used vessels for reconstruction. Clinical examination and a dual phase CT angiogram/MR angiogram can identify vessels available for reconstruction. Arterial options are discussed including tips on using the common carotid artery and the use of Corlett loops for utilizing contralateral arteries. Venous options are also discussed including cephalic vein transposition and Corlett loops. Novel options, such as use of extracorporeal perfusion of flaps have been shown to be effective when all other options have been depleted. SUMMARY: Creative solutions are needed for these extreme circumstances, and reconstructive surgeons need to be aware of the options available to select the best one in each case. Careful planning and having multiple back-up choices is crucial to successful reconstruction in these cases.

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

Outcomes of implant-based oral rehabilitation in head and neck oncology patients-a retrospective evaluation of a large, single regional service cohort.

BACKGROUND: The study reports on implant survival outcomes in head and neck cancer patients who received implant-based oral rehabilitation in a regional service centre. METHODS: A retrospective analysis of implant survival outcomes in patients treated in a regional service from 2012 to 2017 was performed. The primary outcome measure was implant survival. The secondary outcome measure was to assess the effect of covariates associated with implant failure including bone type, radiotherapy, chemotherapy, gender and surgical implant complications. Kaplan-Meier survival curves were applied to compare differences in the survival rates of groups of variables. Cox proportional hazards models were applied to identify covariates associated with implant failure. p value was set at 0.05. RESULTS: The sample was composed of 167 head and neck cancer patients who had 779 dental implants placed. Implant survival estimates were calculated: 3 years, 95.7% [95%CI 94.3-97.2%] and 5 years, 95.5% [95%CI 93.9-97.0%], with a median follow-up of 38 months. Gender (p = 0.09), radiotherapy (p = 0.16) and chemotherapy (p = 0.17) did not significantly influence implant survival, whereas implant failure was higher in transported (reconstructed) bone sites in comparison with native bone (p < 0.01). CONCLUSION: The result of this study suggests that overall implant survival as part of the routine oral rehabilitation is high in this patient cohort; however, implant failure was found to be statistically higher for implant placed into transported bone in comparison to native bone.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Factors affecting prognosis in locoregional recurrence of oral squamous cell carcinoma.

BACKGROUND: Recurrence of oral squamous cell carcinoma (rOSCC) after primary treatment is associated with poor survival outcomes. Salvage treatment with further surgery, radiotherapy and chemotherapy has high morbidity, making patient selection crucial. However, in the recurrence setting, reliable stratification data are scarce. Decision-making in this context is consequently complex. We investigated factors influencing overall survival after rOSCC. METHODS: Retrospective cohort study of patients with rOSCC (n = 83) at the Queen Elizabeth Hospital Birmingham, UK between 2006 and 2016. Associations with overall survival were analysed using univariate and multivariate analyses to identify important clinical prognostic indicators. RESULTS: Overall survival at 1 year was 32.5% and at 5 years was 18.1% after a median follow-up of 7.4 months. Multivariate analysis identified four independent predictors of overall survival following rOSCC: size of primary tumour (HR 2.077; 95% CI 1.034-4.172), extent of recurrent disease (HR 3.286; 95% CI 1.545-6.991), history of moderate alcohol consumption (HR 0.351; 95% CI 0.162-0.763), and close or positive margins at primary resection (HR 1.955; 95% CI 1.063-3.595). CONCLUSIONS: We identified four key factors that help prognostication and risk stratification of rOSCC. Given the high morbidity associated with salvage treatment, we recommend that the multidisciplinary team (MDT) and the patient weigh these factors carefully when considering further treatment. Further investigation of the biology underlying these oncophenotypes may contribute to better patient stratification.

Circulating tumor DNA as a biomarker and liquid biopsy in head and neck squamous cell carcinoma.

The use of circulating biochemical molecular markers in head and neck cancer holds the promise of improved diagnostics, treatment planning, and posttreatment surveillance. In this review, we provide an introduction for the head and neck surgeon of the basic science, current evidence, and future applications of circulating tumor DNA (ctDNA) as a biomarker and liquid biopsy to detect tumor genetic heterogeneity in patients with head and neck squamous cell carcinoma (HNSCC).

Free Bone Grafts for Mandibular Reconstruction in Patients Who Have Not Received Radiotherapy: The 6-cm Rule-Myth or Reality?

Bony reconstruction of the mandible after surgical resection results in improved rehabilitation and aesthetics. Composite tissue transfer has transformed reconstruction, particularly in patients who have received radiotherapy. However, there is morbidity related to free tissue transfer. Free nonvascularized bone grafts have much lower morbidity. Surgeons believe that free bone grafts greater than 6.0 cm are prone to failure. The aims of this study was to assess whether bone grafts greater than 6.0 cm in length have a high risk of failure. A retrospective study was performed on all patients who had free bone grafts greater than 6.0 cm in length at Birmingham, UK, and Florida, the United States. None of the patients received radiotherapy. A total of 14 patients had undergone bone grafts for mandibular defects greater than 6.0 cm in length; 13 of the bone grafts were successful. Of these 13, none were infected and there was radiographic evidence of bony union. Some of the patients have been dentally rehabilitated with implants. Contrary to much of the literature and many surgeons belief, our study has shown that long mandibular defects (>6.0 cm) are not a contraindication to the use of free bone grafts. Key principles to achieve success are discussed in this article.