Impact of the COVID-19 Pandemic on Head and Neck Cancer Management: The Experience of the Maxillo-Facial Surgery Department of a French Regional Referral Center in a High-Incidence Area.

Background: Cancer patients are at a high risk of complications in cases of infection, and head and neck cancers (HNC) are no exception. Since late 2019, SARS-CoV-2 has caused a global health crisis, with high rates and severe forms of the disease in cancer patients. Hospitalization, surgery and radiotherapy were rapidly described as increasing the risk of infection. Since March 2020, the Amiens University Hospital (France) has been taking care of COVID-19 patients while its maxillofacial surgery department managed HNC patients without interruption, even during lockdown periods. However, many questions concerning the impact on patient care were still pending. The aim of this study is to describe HNC management in our center during the first epidemic peak and to evaluate the impact of containment measures on patient treatment. Methods: We retrospectively included 44 HNC patients treated in our department between 1 March and 31 August 2020. Two groups were defined according to the period of care: lockdown (March to May) and lighter restrictions (June to August). Results: The results show typical epidemiological characteristics, maintained management times and non-downgraded procedures. Conclusions: Thus, during the first epidemic peak, continuity of care and patients' safety could be ensured thanks to adequate means, adapted procedures and an experienced surgical team.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients.

BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.

Masseteric nerve position on the "temporomandibular joint-chin tip" artificial axis: an anatomical study.

PURPOSE: The use of the masseteric nerve develops in the surgery of facial paralysis rehabilitation. The objective of this study was to determine the topography of the masseteric nerve and to deduce and predict a precise and reproducible anatomical cluster to facilitate its clinical identification during V-VII neurotization surgery. METHOD: For the purpose of this work, a cadaveric study was performed on 31 hemi-faces. All dissections were performed bilaterally and comparatively, following steps aiming at simulating, as close as possible, the clinical conditions of a facial palsy rehabilitation by V-VII anastomosis. RESULT: For the identification of the masseteric nerve, bony reference points were used, i.e., the temporomandibular joint (TMJ) and the chin point (CT). A virtual axis was drawn between the TMJ and the CT, and the distance [TMJ-MN] determining the smallest length h was then plotted against the distance [TMJ-CT] determining the largest length H, thus allowing the calculation of an h/H proportion ratio (PR) indicating the proximal part of the masseteric nerve from the TMJ. The average length h between the TMJ and the NM was 3.5 cm (± 0.1 cm) from the TMJ, i.e., an average ratio h/H [TMJ-MN]/[TMJ-CT] of 28.1% 4.0 and a median ratio of 28.6% of the distance [TMJ-CT]. CONCLUSION: Our study opens new perspectives for facilitating its identification and use, offering practitioners a tool to make V-VII the neurotization procedure less complex, with the eventual prospect of a minimally invasive procedure combining imaging, surgery, and augmented reality.

Molecular Landscape of the Coagulome of Oral Squamous Cell Carcinoma.

BACKGROUND: Hemostatic complications, ranging from thromboembolism to bleeding, are a significant source of morbidity and mortality in cancer patients. The tumor coagulome represents the multiple genes and proteins that locally contribute to the equilibrium between coagulation and fibrinolysis. We aimed to study the coagulome of Oral Squamous Cell Carcinoma (OSCC) and examine its link to the tumor microenvironment (TME). METHODS: We used data from bulk tumor DNA/RNA-seq (The Cancer Genome Atlas), single-cell RNA-seq data and OSCC cells in culture. RESULTS: Among all tumor types, OSCC was identified as the tumor with the highest mRNA expression levels of F3 (Tissue Factor, TF) and PLAU (urokinase type-plasminogen activator, uPA). Great inter- and intra-tumor heterogeneity were observed. Single-cell analyses showed the coexistence of subpopulations of pro-coagulant and pro-fibrinolytic cancer cells within individual tumors. Interestingly, OSCC with high F3 expressed higher levels of the key immune checkpoint molecules CD274/PD-L1, PDCD1LG2/PD-L2 and CD80, especially in tumor dendritic cells. In vitro studies confirmed the particularity of the OSCC coagulome and suggested that thrombin exerts indirect effects on OSCC cells. CONCLUSIONS: OSCC presents a specific coagulome. Further studies examining a possible negative modulation of the tumor's adaptive immune response by the coagulation process are warranted.

Therapeutic Perspectives for the Perioperative Period in Oral Squamous Cell Carcinoma (OSCC).

The perioperative period is the relatively short window of time, usually measured in days or weeks, around the surgical procedure. Despite its short duration, this time period is of great importance for cancer patients. From a biological point of view, the perioperative period is complex. Synchronous with primary tumor removal, surgery has local and distant consequences, including systemic and local inflammation, coagulation and sympathetic activation. Furthermore, the patients often present comorbidities and receive several medical prescriptions (hypnotics, pain killers, anti-emetics, hemostatics, inotropes, antibiotics). Because of the complex nature of the perioperative period, it is often difficult to predict the oncological outcome of tumor resection. Here, we review the biological consequences of surgery of Oral Squamous Cell Carcinoma (OSCC), the most frequent form of primary head and neck tumors. We briefly address the specificities and the challenges of the surgical care of these tumors and highlight the biological and clinical studies that offer insight into the perioperative period. The recent trials examining neoadjuvant immunotherapy for OSCC illustrate the therapeutic opportunities offered by the perioperative period.

Bilateral bifid condyles: A rare etiology of temporomandibular joint disorders.

Background: Bifid mandibular condyle (BMC) is a rare etiology of temporomandibular joint (TMJ) disorders characterized by a duplication of the head of the mandibular condyle.Case report: The authors report the case of a 20-year-old patient complaining of a painful and clicking TMJ and mandibular hypomobility, which had been progressing for several months. Radiological investigations (dental panoramic radiograph and X-ray CT scan) revealed right and left abnormalities of the TMJ due to bilateral BMC requiring surgical management.Conclusion: Despite a prevalence of 0.31% to 1.82% and the controversies surrounding its pathophysiology, maxillofacial surgeons should be aware of BMC to avoid misdiagnosis related to the clinical presentation (pain, clicking, hypomobility, or ankylosis) and provide adequate management.

Resensitization to Nivolumab after Intratumoral Chemotherapy in Recurrent Head and Neck Squamous Cell Cancer: A Report of 2 Cases.

The survival of patients with head and neck squamous cancer with locoregional recurrence is short if salvage surgery or radiation cannot be performed. Systemic chemotherapy based on platinum salts and cetuximab produces only partial and transient responses. Immune checkpoint inhibitors (i.e., nivolumab) lead to a low complete response rate of only about 10%, but in some cases the effects can be long-lasting. Intratumoral chemotherapy (ITC) has been proposed for patients with local recurrence of head and neck squamous cell carcinoma with an objective response rate of 27-50%. However, it often leads to peritumoral tissue necrosis, and the duration of local control is limited. Here, we present 2 patients with head and neck squamous cell cancer whose local recurrences were refractory to intravenous chemotherapy and nivolumab. ITC using nonnecrotizing molecules, associated with nivolumab, led to complete stable local and distant response. ITC seems to trigger tumor resensitization to previously ineffective immunotherapy. This combination deserves an evaluation in the framework of a prospective trial.

A pain like no other: From cluster to headache to Eagle's syndrome, a case report.

BACKGROUND: Eagle's syndrome, also called stylohyoid complex syndrome, is a rare syndrome pathology characterised by latero-cervical pain radiating to the face, linked to an abnormal enlargement of the styloid or calcification of the stylo-hyoid ligament. CASE: We report here the case of a young man of 25 suffering from cluster headache resistant to treatments, revealing Eagle's syndrome. CONCLUSION: Only surgery led to a real improvement of his condition.

Use of an occlusal splint and intraoperative imaging with an intraoral approach in the management of mandibular subcondylar fractures.

INTRODUCTION: To evaluate the feasibility of safely managing subcondylar fractures using an original surgical procedure combining an intraoral approach, the use of a custom-made occlusal overlay splint, and intraoperative imaging. MATERIALS AND METHODS: Condylar fragment was freed from surrounding soft tissues, was laterally exposed to the ramus, and a miniplate was fixed in place for osteosynthesis. An overlay splint maintaining the dental occlusion was used to facilitate reduction and stabilization during fixation. Intraoperative monitoring by cone-beam computed tomography (CBCT) was performed before completing the fixation. RESULTS: Between November 2018 and June 2019, 10 patients were treated using this procedure. The median length of the proximal condylar fragment was 29 mm (range 24-39 min). Five patients had an associated mandibular fracture. The median duration of the condylar fracture surgery was 54.5 min (range 38-79 min). All patients had satisfactory reduction and osteosynthesis with no complications. CONCLUSION: It is feasible to safely manage subcondylar fractures with this surgical procedure that could facilitate open reduction using intraoral approaches. Occlusal splints maintain downward pressure on the rami bilaterally and symmetrically, helping to anatomically reposition condylar process fractures. Intraoperative imaging is used to monitor this step.

Should a neck dissection be performed on patients with cN0 adenoid cystic carcinoma? A REFCOR propensity score matching study.

BACKGROUND: Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software. RESULTS: Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages. ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity. After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) [48-81]), compared to 73 months (95% CI [52-85]) for patients without ND (HR = 1.33; 95% CI [0.82-2.16]; p = 0.2). CONCLUSION: ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.

Endosteal blood supply of the mandible: anatomical study of nutrient vessels in the condylar neck accessory foramina.

PURPOSE: In the mandible, the condylar neck vascularization is commonly described as mainly periosteal; while the endosteal contribution is still debated, with very limited anatomical studies. Previous works have shown the contribution of nutrient vessels through accessory foramina and their contribution in the blood supply of other parts of the mandible. Our aim was to study the condylar neck's blood supply from nutrient foramina. METHODS: Six latex-injected heads were dissected and two hundred mandibular condyles were observed on dry mandibles searching for accessory bone foramina. RESULTS: Latex-injected dissections showed a direct condylar medular arterial supply through foramina. On dry mandibles, these foramina were most frequently observed in the pterygoid fovea in 91% of cases. However, two other accessory foramina areas were identified on the lateral and medial sides of the mandibular condylar process, confirming the vascular contribution of transverse facial and maxillary arteries. CONCLUSIONS: The maxillary artery indeed provided both endosteal and periosteal blood supply to the condylar neck, with three different branches: an intramedullary ascending artery (arising from the inferior alveolar artery), a direct nutrient branch and some pterygoid osteomuscular branches.

Intraosseous microdialysis for bone free flap monitoring in head and neck reconstructive surgery: A prospective pilot study.

BACKGROUND: Although some researchers have positioned microdialysis catheters in the soft tissue surrounding bone, the results did not accurately reflect bone metabolism. The present study's objective was to establish the feasibility of microdialysis with a catheter positioned directly in bone. METHODS: Thirty-four patients (19 males, 15 females; median age: 59) were included in a prospective, nonrandomized clinical trial in the Department of Maxillofacial Surgery at Amiens-Picardie University Hospital (Amiens, France). Fibula or iliac crest free flaps were used in reconstructive head and neck surgery (for cancer, osteoradionecrosis, trauma, or ameloblastoma) and monitored with microdialysis catheters positioned in a hole drilled into the bone. Glucose, lactate, pyruvate, and glycerol concentrations were analyzed for 5 days. RESULTS: All catheters were positioned successfully, and thrombosis did not occur during the monitoring. In two patients, an increase in the lactate concentration and a glucose level close to 0 were associated with signs of flap necrosis, with removal on Days 9 and 50. In viable flaps, the mean glucose level was 2.02 mmol/L, the mean lactate level was 8.36 mmol/L, and the mean lactate/pyruvate ratio was 53. Forty percent of the glucose values were below 1 mmol/L, and 50% of the lactate/pyruvate ratio values were above 50-suggesting a specific metabolic pattern because these values would be considered as alert values in soft tissue. CONCLUSION: Monitoring bone free flaps with intraosseous microdialysis is feasible. This technique specifically assesses bone viability, and further studies are now necessary to define the alert values in bone.

Quantitative assessment of the flow distribution in the branches of the external carotid by non-injected flow MRI.

Owing to the lack of databases of blood flow distributions in the external carotid branches, surgeons currently rely on per-operative imaging and on their experience to choose the recipient vessels for microsurgical facial reconstructions. But, thanks to three-dimensional phase contrast angiography (PCA) and kinematic CINE phase contrast (PC) sequences, MRI technologies have the potential to provide quantitative anatomical and hemodynamic information without injection of contrast agent. Having developed and optimized PC-MRI sequences for the small facial vessels, our objective was to investigate the haemodynamic and blood flow distribution in the external carotid branches. We included 31 healthy volunteers in an MRI prospective study. Two-dimensional CINE PC-MRI sequences (average duration time of 2 min 40 s ± 24 s) were performed in the external carotid collaterals (n = 290). A statistical analysis of the flow measurements showed that, despite large interpersonal variabilities, a general flow distribution pattern was obtained by dividing the vessel flow rates by the external carotid artery one (providing local percentages of the incoming flow). The vessels could then be classified in three haemodynamic groups (p < 0.05 Student's test): "low flow" group (lingual artery-12.5 ± 5% of incoming flow), "intermediate flow" group (superior thyroid artery-16.5 ± 10%, internal maxillary artery-20.5 ± 11%, superficial temporal artery-18.4 ± 6%), "high flow" group (facial artery -26.6 ± 10%). Thanks to this general flow distribution mapping, it is now possible to estimate the flow rates in the distal branches of any individual from a single blood flow measurement in the external carotid artery.

Influence of principal component analysis acceleration factor on velocity measurement in 2D and 4D PC-MRI.

OBJECTIVE: The objective of the study was to determine how to optimize 2D and 4D phase-contrast magnetic resonance imaging (PC-MRI) acquisitions to acquire flow velocities in millimetric vessels. In particular, we search for the best compromise between acquisition time and accuracy and assess the influence of the principal component analysis (PCA). MATERIALS AND METHODS: 2D and 4D PC-MRI measurements are conducted within two in vitro vessel phantoms: a Y-bifurcation phantom, the branches of which range from 2 to 5 mm in diameter, and a physiological subject-specific phantom of the carotid bifurcation. The same sequences are applied in vivo in carotid vasculature. RESULTS: For a vessel oriented in the axial direction, both 2D and axial 4D PC-MRI provided accuracy measurements regardless of the k-t PCA factor, while the acquisition time is reduced by a factor 6 for k-t PCA maximum value. The in vivo measurements show that the proposed sequences are adequate to acquire 2D and 4D velocity fields in millimetric vessels and with clinically realistic time durations. CONCLUSION: The study shows the feasibility of conducting fast, high-resolution PC-MRI flow measurements in millimetric vessels and that it is worth maximizing the k-t PCA factor to reduce the acquisition time in the case of 2D and 4D axial acquisitions.

3T non-injected phase-contrast MRI sequences for the mapping of the external carotid branches: In vivo radio-anatomical pilot study for feasibility analysis.

An essential stage in head and neck microsurgical reconstruction is the choice of recipient vessels. To make relevant choices, surgeons must rely on accurate imaging techniques. The objective of the study was to examine the feasibility of Phase-Contrast sequences to conduct the pre-operative tests without injection and provide precise radio-anatomical data over the entire vessel region. The challenges were the large velocity range, the lack of contrast, and the large spatial resolution needed to image vessels below 5 mm in diameter. Thirty-one healthy volunteers were included in an MRI prospective study. The anatomical and morphometrical characteristics of the collaterals of the external carotid artery were determined associating 3D PCA and 2D Cine MRI-PC sequences (average protocole duration time of 49 min ± 4 min). The average diameter was measured to be 2.1 ± 1.4 mm for the superior thyroid artery, 2.2 ± 1.1 mm for the lingual artery, 2.7 ± 1.6 mm for the facial artery, 2.6 ± 1.4 mm for the internal maxillary artery, and 2 ± 1.4 mm for the superficial temporal artery. With a vessel identification success rate of 98%, the study showed for the first time that Phase Contrast MRI allowed non-invasive and non-operator dependent anatomical analyses of small caliber vessels without the use of agent contrast. It also proved that the designed sequences could be used on patients and provided valuable pre-operative information for head and neck surgery.