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The present study aimed at assessing the epidemiology including demographic variables, diagnostic features, and management of ameloblastomas at several European departments of maxillofacial and oral surgery. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, site, size, radiographic features, type, histopathological features, kind of treatment, length of hospital stay, complications, recurrence, management and complications of the recurrence. A total of 244 patients, 134 males and 110 females with ameloblastomas were included in the study. Mean age was 47.4 years. In all, 81% of lesions were found in the mandible, whereas 19% were found in the maxilla. Mean size of included ameloblastomas was 38.9 mm. The most frequently performed treatment option was enucleation plus curettage/peripheral ostectomy in 94 ameloblastomas, followed by segmental resection (60 patients), simple enucleation (46 patients), and marginal resection (40 patients). A recurrence (with a mean follow up of 5 years) was observed in 47 cases out of 244 ameloblastomas (19.3%). Segmental resection was associated with a low risk of recurrence (p = 0003), whereas enucleation plus curettage/peripheral ostectomy was associated with a high risk of recurrence (p = 0002). A multilocular radiographic appearance was associated with a high risk of recurrence (p < .05), as well as the benign solid/multicystic histologic type (p < .05). Within the limitations of the study it seems that the management of ameloblastomas will probably remain controversial even in the future. Balancing low surgical morbidity with a low recurrence rate is a difficult aim to reach.

This study aimed to investigate the clinical and prognostic relevance of the Hippo-YAP transactivators YAP1 and TAZ in oral squamous cell carcinoma, and their possible relationship with PI3K/mTOR pathway activation.Immunohistochemical analysis of YAP1, TAZ, PIK3CA (p110α), p-AKT (Ser473), and p-S6 (Ser235) was performed in paraffin-embedded tissue specimens from 165 OSCC patients. Correlations between protein expression and clinical data were further assessed.YAP1 expression was detected in both cytoplasm and nucleus of tumor cells, whereas TAZ expression was only found in the nucleus. Nuclear YAP1 was significantly associated with tumor size (p = 0.03), neck lymph node metastasis (p = 0.02), TNM stage (p = 0.02), and poor differentiation (p = 0.04). Nuclear TAZ was associated with tobacco (p = 0.03) and alcohol consumption (p = 0.04), and poor tumor differentiation (p = 0.04). There was a positive significant correlation between nuclear and cytoplasmic YAP1, nuclear TAZ, p110α expression, and mTORC1 activation p-S6 (S235). Combined expression of nuclear and cytoplasmic YAP1 was prognostic in both univariate and multivariate analyses. Active nuclear YAP1 was significantly and independently associated with poor disease-specific (p = 0.005, HR = 2.520; 95% CI = 1.319-4.816) and overall survival (p = 0.015, HR = 2.126; 95% CI = 1.155-3.916).Nuclear YAP1 is an independent predictor of poor survival in oral squamous cell carcinoma.

The radial forearm free flap (RFFF) and ulnar forearm free flap (UFFF) are used in head and neck reconstruction because they provide a thin and pliable skin paddle as well as a long vascular pedicle. However, in spite of several studies showing the safety of the UFFF, the RFFF is more popular among reconstructive surgeons based on concerns about hand ischaemia. A prospective study was designed in which 10 UFFF and 11 RFFF surgeries were performed in 20 patients undergoing oral cavity reconstruction between January 2017 and July 2018. Hand vascular parameters were evaluated preoperatively and postoperatively using Doppler ultrasound and plethysmography. The preoperative and postoperative diameters of the radial and ulnar arteries, and the flow velocities through the remainder of the forearm artery were measured preoperatively and at 3 months postoperative. Additionally, a comparison was performed between the preoperative and postoperative fingertip perfusion values according to impedance plethysmography. The preoperative mean diameter of the radial artery (2.89±0.47mm) was significantly greater than that of the ulnar artery (2.35±0.48mm) at the level of the wrist; however, 3 months after the surgery, the mean diameters of the two arteries did not differ significantly. There were no differences in digital perfusion when a UFFF was used compared with an RFFF.

Hardware complications (loosening of screws, infection, or exposure of the plate) in mandibular reconstruction with vascularized osseous free flaps impose significant morbidity, and frequently require revision surgery. Purpose of this study was to identify possible contributing factors for hardware complications.This is a retrospective cohort study involving case series of patients who underwent microvascular mandible reconstructions between 2000 and 2020. Patient demographics, pathological, clinical, and treatment-related factors were analyzed in univariate and multivariate analyses.Ninety-one patients were enrolled, encompassing 63 reconstructions with fibular free flaps, 26 reconstructions with scapular, and 2 reconstructions with iliac flaps. Rate of hardware complications and plate exposure was 14.3% and 7.7%, respectively, with a median follow-up time for extrusion of 29 months. In univariate analysis, preoperative radiotherapy (odds ratio [OR] = 6.57, p = .01), and secondary mandible reconstruction (OR = 4.3, p = .04) were significant predictors of hardware complications, and plate exposure was most frequently found in secondary reconstruction (37.5%, OR = 11.8, p = .04). Hypertension was the most commonly found comorbidity (24%), and it trended toward significance regarding plate exposure (p = .05). Only secondary mandible reconstruction was associated with osteosynthesis complications (OR = 12.53, p = .01) and plate exposure (OR = 23.86, p = .005) on multivariate analysis, while preoperative radiation therapy did not retain its relevance on plate exposure.Secondary mandible reconstructions with vascularized osseous free flaps have a higher risk of osteosynthesis complications than primary reconstructions.

The objective of the present study was to assess the epidemiology including demographic variables, diagnostic features, and the management of odontogenic keratocyst (OKCs) at several European departments of maxillofacial and oral surgery. This study is based on a systematic computer-assisted database that allowed the recording of data from treated OKCs. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, site, size, radiographic features, treatment of OKCs, length of hospital stay, complications, recurrence, management and complications of eventual recurrence. A total of 405 patients, 249 male and 156 female, with 415 OKCs (407 sporadic and 8 syndromic lesions) were included in the study: 320 lesions were found in the mandible, whereas 95 were found in the maxilla. In the mandible, the most frequently involved subsite was the angle, whereas in the maxilla it was the molar region. The most frequently performed treatment option was enucleation plus curettage/peripheral ostectomy in 204 OKCs (recurrence rate, 9%). Decompression without residual cystectomy (recurrence rate, 66%), marsupialization with residual enucleation with the use of Carnoy's solution (recurrence rate, 50%), decompression with residual cystectomy (recurrence rate, 43%), and simple enucleation (recurrence rate, 24%) were the treatment options with the highest recurrence rates. An appropriate management of odontogenic keratocysts should be individualized, taking into consideration clinical and radiological findings, as well as patients’ age and comorbidities.

INTRODUCTION: The aim of the present article was to review and depict the main radiological features of odontogenic keratocysts (OKCs), thus helping the differential diagnoses from other odontogenic cysts and neoplasms. EVIDENCE ACQUISITION: A review of articles published between January 2000 and October 2020 using Medline and the MeSH Term "odontogenic keratocyst" in combination with the following terms "imaging," "radiology," "panoramic radiograph," and "computed tomography," was performed. EVIDENCE SYNTHESIS: Radiographically, OKCs are well-defined unilocular or multilocular radiolucencies bounded by corticated margins. Most lesions are unilocular; instead, multilocular OKCs represent about the 30% of cases, mainly involving the posterior mandible. When, particularly in large lesions, OKCs display a multilocular presentation with adjacent satellite cysts (daughter cysts) a "soap-bubble appearance" can be recognized. DISCUSSION: Panoramic radiograph and CT still play an important role in the diagnosis and treatment planning of OKCs. Unfortunately, it may not be easy to differentiate OKCs from other odontogenic lesions, especially when they are small and unilocular. CONCLUSIONS: Histopathological findings are still necessary to obtain a definitive diagnosis.

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4+, CD8+ and FOXP3+ TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed. CD4+ and CD8+ TILs are significantly associated with smoking and alcohol habits. CD4+ and CD8+ TILs show an inverse relationship with NANOG and SOX2 expression, and FOXP3+ TILs is significantly correlated with Nestin and PDPN expression. High infiltration of CD4+ and CD8+ TILs and a high tumoral CD8+/FOXP3+ ratio are significantly associated with tumors harboring positive PD-L1 expression. Infiltration of stromal/tumoral FOXP3+ TILs and a low stromal CD8+/FOXP3+ ratio are significantly associated with better disease-specific survival. Multivariate analysis reveals that the stromal CD8+/FOXP3+ TILs ratio is a significant independent prognostic factor. Regarding OSCC patient survival, the CD8+/FOXP3+ TILs ratio is an independent prognostic factor. TILs may act as biomarkers and potential therapeutic targets for OSCC.

Background/aims: When facial trauma involves elderly patients, the possible presence of frailty and comorbidities in victims of trauma may worsen the posttraumatic symptoms and decrease quality of life. The aim of this multicenter study was to assess the quality of life following surgical or non-operative management of maxillofacial trauma in elderly patients. Materials and methods: This cohort study was based on the administration of validated self-administered questionnaires to all the geriatric patients (70 years or more) with facial fractures from the involved maxillofacial surgical units across Europe, since 1st January 2019 to 31st June 2019. The following questionnaires were administered: SF36 questionnaire; the VFQ-25 questionnaire; the Oral Health Impact Profile – 14 (OHIP14). Outcome variables were VFQ-25 and OHIP-14 results. Results: A total of 37 patients (14 male and 23 female patients) met the inclusion criteria and were included in the study. Elderly patients had an improvement in almost all the categories examined by the SF-36 questionnaire 6 months after trauma, with the only exception of a worsening as for role limitations due to physical health. An improvement was observed in almost all the categories at SF-36 test. A worsening of scores of OHIP-14 for all the considered dimensions in the whole study population was observed too. Conclusions: Elderly patients following facial trauma experience significant emotional, social, and functional disturbances. We observed that emotional problems, energy/fatigue, social functioning, and generally social limitations played a great role in the decrease of QoL in elderly patients following maxillofacial trauma.

Simple Summary The complex interplay between the different cellular components in the tumor microenvironment (TME) dynamically modulates the antitumor immune response. This study investigates the prognostic relevance of CD20+ tumor-infiltrating B lymphocytes in oral squamous cell carcinoma (OSCC), and also possible relationships with other immune subtypes and key players within the oral TME. Abstract Immunohistochemical analysis of stromal/tumoral CD20+ B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20+ B lymphocytes and other immune profiles (i.e., CD4+, CD8+, and FOXP3+ TILs, and CD68+ and CD163+ macrophages) both in stroma and tumor nests. Strikingly, CD20+ TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20+ TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20+ TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8+ TILs, low tumoral infiltration by CD68+ macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20+ TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003; and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20+ TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20+ TILs and CSC marker expression.

Background/Aims Management of maxillofacial trauma in the geriatric population poses a great challenge due to anatomical variations and medical comorbidities. The aim of this study was to analyze the management variables, timing, and outcomes of facial fractures in elderly patients (aged 70 years or more) at several European departments of oral and maxillofacial surgery. Materials and Methods This study was based on a systematic computer-assisted database that allowed the recording of data from all geriatric patients with facial fractures from the involved maxillofacial surgical units across Europe between 2013 and 2017. Results A total of 1334 patients were included in the study: 665 patients underwent closed or open surgical treatment. A significant association (P lt .005) was found between the presence of concomitant injuries and a prolonged time between hospital admission and treatment. The absence of indications to treatment was associated with comorbidities and an older age (P lt .000005). Conclusions Elderly patients require specific attention and multidisciplinary collaboration in the diagnosis and sequencing of trauma treatment. A prudent attitude may be kept in selected cases, especially when severe comorbidities are associated and function is not impaired., Peer-reviewed manuscript: [http://smile.stomf.bg.ac.rs/handle/123456789/2528]

INTRODUCTION: Management of body fractures in patients with edentulous atrophic mandibles represents a challenging task due to patient's age, medical comorbidities, poor bone quality, and vascularity, as well as reduced contact area between the fracture ends. The aim of the study was to assess the demographic and clinical variables, the surgical technique, and outcomes of unilateral body fractures of the edentulous atrophic mandible managed at several European departments of oral and maxillofacial surgery.METHODS: This study is based on a systematic computer-assisted database that allowed the recording of data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between 2008 and 2017. The following data were recorded for each patient: gender, age, comorbidities, etiology, synchronous body injuries, degree of atrophy of the mandible according to Luhr classification, type of surgical approach and fixation, length of hospitalization, and presence and type of complications.RESULTS: A total of 43 patients were included in the study: 17 patients' mandibles were classified as class I according to Luhr, 15 as class II, and 11 as class III. All patients underwent open reduction and internal fixation by extraoral approach in 25 patients, intraoral in 15 patients, and mixed in 3 patients. A single 2.0 miniplate was used in 16 patients, followed by a single 2.4 reconstruction plate in 13 patients, by two 2.0 miniplates, and three 2.0 miniplates. Outcome was considered to be satisfying in 30 patients, with no complications. Complications were observed in 13 cases.CONCLUSIONS: Treatment of unilateral body fractures of the edentulous mandible must still be based on the type of fracture, degree of atrophy, experience of the surgeon, and patients' preference. An adequate stability can be obtained by different plating techniques that have to be appropriately tailored to every single specific patient.

Background The purpose of this study was to investigate the clinical relevance of phosphorylated ribosomal protein S6 (p-S6), a surrogate marker of mammalian target of rapamycin (mTOR) activation, and p21 in a series of 125 patients with oral squamous cell carcinomas (OSCCs). Methods Immunohistochemical analysis was performed to ascertain the phosphorylation status of p-S6 at Ser235/236 and Ser240/244, p21, and p53 protein expression. Results Expression of phosphorylated S6 protein on either serine 235/236 or serine 240/244 was detected in 83% and 88% tumors, respectively, and both of them were inversely and significantly correlated with the tumor size and local infiltration. Positive p21 expression was found in 91.5% of the cases, and was inversely correlated with tumor size. In OSCC, p21 expression correlates with p-S6 levels, a surrogate marker of mTOR activation, independently of p53 status. Conclusion Expression of both p21 and p-S6 was found to inversely associate with tumor size but not survival outcomes in patients with OSCC.

Tumor-associated macrophages (TAMs) can be polarized into antitumoral M1 and protumoral and immunosuppressive M2 macrophages. This study investigated the clinical relevance of TAM infiltration in oral squamous cell carcinoma (OSCC), evaluating CD68 (M1 and M2 macrophage marker) and CD163 expression (M2 macrophage marker) in the tumor nests and surrounding stroma. Immunohistochemical analysis of both stromal/tumoral CD68+ and CD163+ TAMs was performed in paraffin-embedded tissue specimens from 125 OSCC patients, and correlated with clinical data. Potential relationships with the expression of cancer stem cell (CSC) markers and PD-L1 in the tumors were also assessed. Stromal CD163+ infiltration was significantly associated with the tumor location in the tongue, and stromal and tumoral CD68+ and CD163+-infiltrating TAMs were more abundant in nonsmokers and non-alcohol-drinkers. Strikingly, this study uncovers an inverse relationship between CD68+ and CD163+ TAMs and CSC marker expression (NANOG and SOX2) in OSCC. High infiltration of CD163+ TAMs in both tumor and stroma was strongly and significantly correlated with the absence of NANOG expression. Moreover, infiltration of both CD68+ and CD163+ TAMs was also significantly associated with high tumor expression of PD-L1. Our results suggest that there is a link between TAM infiltration and immune escape in OSCC.

INTRODUCTION: The objective of the present study was to assess the demographic variables, causes, and patterns of edentulous atrophic fractures of the mandible managed at several European departments of oral and maxillofacial surgery. The results of this multicenter collaboration over a 10-year period are presented.METHODS: The data of all patients with fractures of the atrophic edentulous mandible from the involved maxillofacial surgical units across Europe between January 1, 2008, and December 31, 2017 were recorded: gender; age; voluptuary habits; comorbidities; etiology; fracture sites; synchronous body injuries; atrophy of the mandible according to Luhr classification; eventual type of treatment; timing of the eventual surgery; length of hospital stay.RESULTS: A total of 197 patients (86 male and 111 female patients) with 285 mandibular fractures were included in the study. Mean age of the study population was 75 years. Statistically significant associations were found between Luhr classes I - II and condylar fractures on one hand (p < .0005), and between Luhr class III and body and parasymphyseal fractures on the other hand (p < .05). Finally, 135 patients underwent open reduction and internal fixation, 56 patients did not undergo any intervention, and 6 patients underwent closed reduction. No statistically significant association was observed between treatment, timing of treatment, comorbidities, and concomitant injuries.CONCLUSIONS: The management of edentulous atrophic mandibular fractures remains challenging. Treatment decisions should continue to be based on the clinician's previous experience and on the degree of bone resorption in edentulous mandible in relation to fracture subsites.

Potentially malignant oral lesions, mainly leukoplakia, are common. Malignant transformation varies widely, even in the absence of histological features such as dysplasia. Hence, there is a need for novel biomarker-based systems to more accurately predict the risk of cancer progression. The pluripotency transcription factor SOX2 is frequently overexpressed in cancers, including oral squamous cell carcinoma (OSCC), thereby providing a link between malignancy and stemness. This study investigates the clinical relevance of SOX2 protein expression in early stages of oral carcinogenesis as a cancer risk biomarker, and also its impact on prognosis and disease outcome at late stages of OSCC progression. SOX2 expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and in 125 patients with OSCC, and correlated with clinicopathological data and outcomes. Nuclear SOX2 expression was detected in four (7%) cases of oral epithelial dysplasia, using a cut-off of 10% stained nuclei, and in 16 (29%) cases when any positive nuclei was evaluated. Univariate analysis showed that SOX2 expression and histopathological grading were significantly associated with oral cancer risk; and both were found to be significant independent predictors in the multivariate analysis. Nuclear SOX2 expression was also found in 49 (39%) OSCC cases, was more frequent in early tumor stages and N0 cases, and was associated with a better survival. In conclusion, SOX2 expression emerges as an independent predictor of oral cancer risk in patients with oral leukoplakia. These findings underscore the relevant role of SOX2 in early oral tumorigenesis rather than in tumor progression.

NANOG, a key regulator of pluripotency and self-renewal in embryonic and adult stem cells, is frequently overexpressed in multiple cancers, including oral squamous cell carcinoma (OSCC). It has been frequently associated with poor outcomes in epithelial cancers, and recently implicated in laryngeal tumorigenesis. On this basis, we investigated the role of NANOG protein expression as an early cancer risk biomarker in oral potentially malignant disorders (OPMD), and the impact on prognosis and disease outcomes in OSCC patients. NANOG expression was evaluated by immunohistochemistry in 55 patients with oral epithelial dysplasia, and 125 OSCC patients. Correlations with clinical and follow-up data were assessed. Nuclear NANOG expression was detected in 2 (3.6%) and cytoplasmic NANOG expression in 9 (16.4%) oral dysplasias. NANOG expression increased with the grade of dysplasia. Cytoplasmic NANOG expression and the histopathological grading were significantly correlated with oral cancer risk, although dysplasia grading was the only significant independent predictor of oral cancer development in multivariate analyses. Cytoplasmic NANOG expression was also detected in 39 (31%) OSCC samples. Positive NANOG expression was significantly associated with tobacco and alcohol consumption, and was more frequent in pN0 tumors, early I-II stages. These data unveil the clinical relevance of NANOG in early stages of OSCC tumorigenesis rather than in advanced neoplastic disease. NANOG expression emerges as an early predictor of oral cancer risk in patients with OPMD.

The aim of this study was to analyze the prevalence of high-risk HPV in oral squamous cell carcinoma (OSCC) in a northern Spanish population, as well as to ascertain the prognostic role of p16INK4a expression. The examination samples were collected from paraffin tissue blocks, from 125 patients surgically treated between 1996 and 2007. All cases were histologically evaluated, and the presence of HPV was assessed by p16 and p53immunohistochemistry followed by DNA detection by in situ hybridization (ISH) and polymerase chain reaction (PCR) amplification using the combination of consensus primers MY11/GP6 + . Fourteen cases (11 %) were p16-immunopositive, and p53 was scored positive in 73 cases (58 %). Five cases (4 %) showed a simultaneous p16-positive and p53-negative immunostaining. ISH was negative in all the cases. Among the p16INK4a-immunopositive cases, PCR amplification failed to reveal HPV DNA in any tumor samples. There were no statistically significant differences in any clinical or pathological characteristics of the patients regarding p16INK4a expression. T classification, neck-node metastasis, and clinical stage showed outcome relevance. However, no significant differences in cause-specific survival based on p16INK4a were observed. We did not find any high-risk HPV types in our patients, thus, are unlikely that HPV has an important role in the etiology of OSCC. p16INK4a protein was neither an accurate marker of HPV infection nor a prognosis marker in OSCC.

Background HERG1 potassium channel plays a critical role in the cell proliferation. Methods HERG1 protein expression was analyzed by immunohistochemistry (IHC) in 62 patients with oral leukoplakias and 100 patients with oral squamous cell carcinomas (OSCC). HERG1 mRNA levels were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 patients with primary head and neck squamous cell carcinoma (HNSCC). Results Statistically significant associations were found between HERG1 expression and tobacco consumption, disease stage, tumor differentiation, tumor recurrence, and reduced survival. There was no association between HERG1 expression and the risk of progression from oral leukoplakia to OSCC. In addition, a high proportion of tumors (80%) showed increased HERG1 mRNA levels compared to normal mucosa from nononcologic patients. Conclusion Aberrant HERG1 expression increases as oral tumorigenesis progresses from oral hyperplasia to OSCC. Increased HERG1 mRNA levels were also frequently detected in OSCC and other HNSCC subsites. HERG1 expression emerges as a clinically relevant feature during tumor progression and a potential poor prognostic biomarker for OSCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Immunohistochemical analysis of stromal/tumoral CD20+ B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20+ B lymphocytes and other immune profiles (i.e., CD4+, CD8+, and FOXP3+ TILs, and CD68+ and CD163+ macrophages) both in stroma and tumor nests. Strikingly, CD20+ TILs were inversely correlated with NANOG/SOX2 expression. Stromal CD20+ TILs were significantly associated with T classification and second primary tumors. A stratified survival analysis showed that tumoral CD20+ TILs were significantly associated with prognosis in male and younger patients, with tobacco or alcohol consumption, high tumoral CD8+ TILs, low tumoral infiltration by CD68+ macrophages, positive PD-L1 expression, and negative NANOG/SOX2. Multivariate Cox analysis further revealed clinical stage and tumoral CD20+ TILs independently associated with disease-specific survival (HR = 2.42, p = 0.003, and HR = 0.57, p = 0.04, respectively). In conclusion, high CD20+ TIL density emerges as an independent good prognostic factor in OSCC, suggesting a role in antitumor immunity. This study also uncovered an inverse correlation between CD20+ TILs and CSC marker expression.

INTRODUCTION: The progressive aging of European population seems to determine a change in the epidemiology, incidence and etiology of maxillofacial fractures with an increase in the frequency of old patients sustaining craniofacial trauma. The objective of the present study was to assess the demographic variables, causes, and patterns of facial fractures in elderly population (with 70 years or more).MATERIALS AND METHODS: The data from all geriatric patients (70 years or more) with facial fractures between January 1, 2013, and December 31, 2017, were collected. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, etiology, site of facial fractures, synchronous body injuries, Facial Injury Severity Score (FISS).RESULTS: A total of 1334 patients (599 male and 735 female patients) were included in the study. Mean age was 79.3 years, and 66% of patients reported one or more comorbidities. The most frequent cause of injury was fall and zygomatic fractures were the most frequently observed injuries. Falls were associated with a low FISS value (PCONCLUSIONS: This study confirms the role of falls in the epidemiology of facial trauma in the elderly, but also highlights the frequency of involvement of females, and the high frequency of zygomatic fractures.

Background: The immune checkpoint PD-1 and its ligand PD-L1 are involved in the induction of immunological tolerance of solid tumors including oral squamous cell carcinoma (OSCC). The aim of the study was to establish the clinical and prognostic significance of PD-L1 in OSCC. Methods: Tissue microarrays of 125 resected OSCC were stained with two different commercially available PD-L1 antibodies (clones E1L3N and 22C3), alongside PD-1 immunostaining. Results: PD-L1 expression in more than 10% of tumor cells was associated with poorer survival, and established as a clinically relevant cut-off point. This relevant PD-L1 expression was detected in 10% to 15% OSCC specimens depending on the anti-PD-L1 antibody, and showed an inverse correlation with tobacco and alcohol consumption. We consistently found that PD-L1 expression was associated with tumor recurrence and lower disease-specific survival. Multivariate analysis further revealed that neck node metastasis (HR 2.304; P = 0.009) and tumor PD-L1 expression (HR 2.571; P = 0.01) were significant independent factors for poor prognosis. Conclusions: PD-L1 expression in more than 10% of tumor cells was a significant and independent factor of poor prognosis in OSCC. Impact: PD-L1 expression in more than 10% of tumor cells was consistently established as a clinically relevant cut-off point by using two different antibodies. Remarkably, PD-L1 expression emerges as an independent poor prognosis marker in patients with OSCC.

Background The purpose of this study was to determine the prevalence of level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs). Material and Methods A prospective analysis of 56 patients with OSCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection was performed. During neck dissection, level IIb lymph nodes were separately removed and processed. Neck dissection was bilateral in 26 patients (46%) and unilateral in 30 patients (54%). Results The mean number of nodes found in the level IIb specimens was 4.7 (range: 0-8 nodes). The prevalence of metastasis at level IIb was 0% in pN0 necks and 3.4% in pN+ necks, with an overall prevalence of 1.8%. A significant association between metastasis to level IIb and type of neck dissection was observed. There were no isolated metastases to level IIb without the involvement of other nodes in the remaining neck specimen. Four regional recurrences were observed during follow-up. Conclusions Based on our findings, we suggest that dissection of the level IIb region in patients with OSCC may be required only in patients with multilevel neck metastasis or if level IIa metastasis is found intraoperatively. Key words: Oral squamous cell carcinoma, neck dissection, level IIb, metastasis, spinal accessory nerve.

Recent studies have identified podoplanin, a mucin-type transmembrane glycoprotein, as a biomarker for oral cancer risk in patients with oral leukoplakia (OPL). The aim of this study was to investigate the potential association between podoplanin and the risk of malignant transformation of OPL with epithelial dysplasia.In this retrospective study, podoplanin immunoexpression was analyzed in 58 patients with oral leukoplakia that showed epithelial dysplasia. Lesions with podoplanin expression in the basal and suprabasal layers of oral epithelium at one area or showing suprabasal expression at two or more areas were considered as positive. Association between podoplanin expression and oral cancer development was analyzed.Twenty-two of the 58 lesions (38%) were classified as podoplanin-positive, and the remaining 36 (62%) lesions were considered podoplanin-negative. The expression of podoplanin was correlated with the grade of dysplasia (p0.0005), and with the risk of progression to oral cancer (p0.0005). In multivariate survival analysis, only premalignant oral lesions displaying positive podoplanin expression showed a significantly increased risk of developing an oral squamous cell carcinoma (hazard ratio=8.738, p=0.007).Podoplanin could be a valuable biomarker for risk assessment of malignant transformation in patients with OPL along with histological assessment.

The purpose of this study was to investigate the clinical relevance of phosphorylated ribosomal protein S6 (p-S6), a surrogate marker of mammalian target of rapamycin (mTOR) activation, and p21 in a series of 125 patients with oral squamous cell carcinomas (OSCCs).Immunohistochemical analysis was performed to ascertain the phosphorylation status of p-S6 at Ser235/236 and Ser240/244, p21, and p53 protein expression.Expression of phosphorylated S6 protein on either serine 235/236 or serine 240/244 was detected in 83% and 88% tumors, respectively, and both of them were inversely and significantly correlated with the tumor size and local infiltration. Positive p21 expression was found in 91.5% of the cases, and was inversely correlated with tumor size. In OSCC, p21 expression correlates with p-S6 levels, a surrogate marker of mTOR activation, independently of p53 status.Expression of both p21 and p-S6 was found to inversely associate with tumor size but not survival outcomes in patients with OSCC.

Summary There is a need for novel and accurate biomarkers based on genetic abnormalities capable of predicting the risk of malignant transformation of epithelial lesions of the oral cavity. Therefore, we investigate the role of cortactin and focal adhesion kinase (FAK) protein expression in oral dysplasias and their potential utility as cancer risk markers. Cortactin and FAK expression were immunohistochemically evaluated in 64 patients with oral epithelial dysplasia. During follow-up, 17 of 64 patients developed an oral squamous cell carcinoma (OSCC). Increased immunoexpression of cortactin and FAK was found in 52 and 27 of 64 oral dysplasias, respectively, and the expression of both proteins increased with the grade of dysplasia. Increased cortactin and FAK expression was also observed in 13 and 15 OSCC, respectively. Overall, cortactin and FAK expression was maintained or further augmented in the oral squamous cell carcinoma compared to the patient-matched preinvasive lesion. Univariate analysis showed that cortactin and FAK expression, as well as histological grading were significantly associated with oral cancer risk. Strong coexpression of both proteins reflected a significantly higher cancer risk than that of weak to moderate expression or than whenever only one of those proteins showed a strong expression. In multivariate analysis, premalignant oral lesions which exhibited a high coexpression of cortactin and FAK showed a significant risk of developing an OSCC (HR = 6.298). Our results indicate that strong immunoexpression of cortactin and FAK, and not only one of them, is a predicting factor for increased cancer risk in oral premalignant lesions.

HERG1 potassium channel plays a critical role in the cell proliferation.HERG1 protein expression was analyzed by immunohistochemistry (IHC) in 62 patients with oral leukoplakias and 100 patients with oral squamous cell carcinomas (OSCC). HERG1 mRNA levels were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 patients with primary head and neck squamous cell carcinoma (HNSCC).Statistically significant associations were found between HERG1 expression and tobacco consumption, disease stage, tumor differentiation, tumor recurrence, and reduced survival. There was no association between HERG1 expression and the risk of progression from oral leukoplakia to OSCC. In addition, a high proportion of tumors (80%) showed increased HERG1 mRNA levels compared to normal mucosa from nononcologic patients.Aberrant HERG1 expression increases as oral tumorigenesis progresses from oral hyperplasia to OSCC. Increased HERG1 mRNA levels were also frequently detected in OSCC and other HNSCC subsites. HERG1 expression emerges as a clinically relevant feature during tumor progression and a potential poor prognostic biomarker for OSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Aims The expression of the voltage-gated potassium channel Kv3.4 was investigated in both oral squamous cell carcinomas (OSCC) and oral leucoplakias to establish its clinical significance during the development and progression of OSCC. Materials and methods Tissue specimens from 62 patients with oral leucoplakia were collected prospectively and 100 patients with OSCC who underwent surgical treatment were collected retrospectively, and Kv3.4 expression was analysed by immunohistochemistry. Results Thirty-nine of 100 tumours exhibited Kv3.4-positive expression, and staining was associated with the degree of differentiation (P = 0.05) but showed no impact on patient prognosis. Abnormal Kv3.4 expression was detected in 16% (7 of 43) hyperplastic lesions and at a significantly higher proportion in oral dysplasias (50%, 8 of 16 cases; P = 0.008), whereas expression was negligible in normal adjacent epithelia. Furthermore, patients carrying Kv3.4-positive lesions exhibited a higher progression risk than those with Kv3.4-negative lesions; however, histology but not Kv3.4 expression predicted oral cancer development significantly in this prospective cohort. Conclusion This study provides original evidence to demonstrate the early occurrence and high prevalence of abnormal Kv3.4 expression in oral leucoplakias. Our results support a role for Kv3.4 potassium channel in OSCC tumorigenesis rather than tumour progression and disease outcome.

Claudin dysregulation has been described in various tumor types; however, its clinical relevance is poorly understood. We present a study in which we assessed the expression of claudin 1 (CLDN1) and CLDN4 in oral squamous cell carcinoma (OSCC), as well as their prognostic relevance. Immunohistochemical analysis of CLDN1 and CLDN4 expression was carried out on tissue sections from 65 OSCCs. The presence of CLDN1 in the invasive front of tumor islands was associated with neck node metastasis, and the expression of CLDN4 was associated with higher histological grade, and tumor recurrence. Membranous staining for CLDN4 in tumor cells, and weak intensity of CLDN4 immunoexpression were predictive for poorer survival. In a multivariate analysis for disease recurrence, CLDN1 immunostaining was statistically significant. Specifically, CDLN1 expression in the tumor invasive front was associated with tumor recurrence. Our results indicate that CLDN4 expression is correlated with poor prognosis, and CLDN1 expression may be an indicator of recurrence of OSCC.

Podoplanin is involved in actin remodeling of the cytoskeleton of tumor cells and may promote tumor cell invasion by increasing cell motility and formation of filopodia-like membrane protrusions. Podoplanin is expressed in a variety of tumors, but its role in head and neck cancer, particularly in oral squamous cell carcinoma, remains unclear. We studied podoplanin expression by immunohistochemistry in 92 oral squamous cell carcinomas (OSCC) using a monoclonal antibody against an epitope of podoplanin (D2-40). In terms of the number of stained cells, 34 OSCC (38 %) had low podoplanin expression (less than 33 % of cells), 33 (36 %) showed moderate expression (between 34 and 66 % of cells), and 21 (22 %) showed high expression. The intensity of immunostaining was strong in 26 (28 %) cases, moderate in 36 (40 %), and weak or negative in the remaining 30 tumors (32 %). Immunohistochemical expression of podoplanin was associated with a tumor histological grade. A diffuse pattern of podoplanin expression significantly decreased in moderately differentiated (37 %) and poorly differentiated (20 %) carcinomas compared to well-differentiated (43 %) carcinomas. In addition, the focal expression of podoplanin in the invasion front of the tumor, without expression in the tumor center, was observed in 72 % of well-differentiated tumors, 27 % of moderate tumors, and 0 % of poorly differentiated tumors. Moreover, a trend was found toward an association of diffuse podoplanin staining with the development of second primary carcinomas (13 %), in contrast to its expression in the invasion front (3 %). No association was observed between podoplanin expression and nodal metastasis.

Inflammatory myofibroblastic tumor (IMT) is a rare mass-forming lesion characterized by fibroblastic or myofibroblastic spindle cell proliferation with varying degrees of inflammatory cell infiltration. Although it has been reported in virtually every organ in the body, the lung is the most common site of involvement. Extrapulmonary IMTs, although rare, have been reported and are characterized by different, more aggressive behavior. We report an extremely rare case of maxillary metastases of pulmonary IMT. Lung IMT was initially misdiagnosed, and oral lesion mimicked clinically and radiologically a radicular cyst. On histologic examination, cells exhibited diffuse and intense immunoreactivity forα-smooth muscle actin and vimentin whereas both pulmonary and oral IMTs presented absence of cellular atypia and lack of expressivity of oncogenic determinants. Distant metastases of lung IMT are extremely unusual, and this is the first report to our knowledge with this particular clinical course. Despite the possibility that the present case could also represent a metachronous multifocal IMT, with pulmonary and extrapulmonary lesions, similar histopathological and immunohistochemical patterns in lung and maxillary region suggest a metastatic course.

Orbital tumors can present with different symptoms, especially ophthalmic disturbances. We describe 1 patient with an orbital metastasis from prostate carcinoma presenting with proptosis and give details of his presentation, diagnostic tools, and treatment. This is a rare case. Possible ocular spread of prostate adenocarcinoma and the diagnostic techniques used are discussed. It is stressed that immunohistochemical studies and comparison with primary tumor may be essential for a definitive diagnosis. The treatment of prostate orbital metastases is also reviewed.

Purpose The purpose of the present study was to assess the effect of free-flap reconstruction on the survival of patients treated for oral squamous cell carcinoma. Patients and Methods The present study was based on a retrospective cohort of 98 patients. Of the 98 patients, 49 underwent surgical reconstruction with microvascular tissue transfer (test group) and in 49 (control group), only local or regional flaps were used. Results For the free-flap group, the average follow-up period was 34.6 months. For the control group, the average follow-up was 39.8 months. At the end of the follow-up period, 23 (47%) and 33 (67.3%) patients had died of oral squamous cell carcinoma in the microvascular reconstructive and control group, respectively. The difference in the final status between the 2 groups was statistically significant ( P = .03). In the free-flap group, the mean and median survival time was 65 and 60 months. In the locoregional flap group, the mean and median survival time was 54 and 24 months, respectively. No difference was seen in the survival time between the free-flap and local flap groups ( P = .2). Univariate Kaplan-Meier analysis revealed that positive surgical margins were significantly associated with shortened survival in the free-flap group and that recurrence was significant in both reconstructive groups. On multivariate Cox regression analysis, the status of the resection margin ( P = .07) and tumor recurrence ( P Conclusion Patients with free-flap reconstruction of surgically created defects after oral cancer resection showed a trend toward better 5-year survival.

Purpose Free flaps have proved to be superior in both functionality and aesthetics in front of classical treatment with locoregional flaps in the treatment of patients with large tumors in the oral cavity. The aim of the present study is to assess if free-flap reconstruction is an economically profitable option. Material and methods The present study was based on a retrospective cohort of 60 patients. Of the 60 patients, 30 underwent surgical reconstruction with microvascular tissue transfer and in 30 only local or regional flaps were used. The 6 months of which the overall management costs according to the hospital perspective were calculated were divided into three periods: operative period, the postoperative phase, follow-up during first 6 months. The following outcome variables were analyzed: operative time; blood loss; admission length, including intensive care unit; complications; secondary interventions; readmissions; and feeding status. Cumulative costs were calculated. Statistical analysis was applied. Results Total estimated costs within the first 6 month were comparable in both. The lower costs of hospital admission in the postoperative phase outweighed the higher costs of the surgical procedure in free flap group when compared with local flaps patients. Conclusions In experienced centers, the reconstruction using free flaps in patients treated for tumors of the oral cavity is safe, improves patient quality of life and is economically sustainable. Forty patients who underwent immediate free radial forearm flap reconstruction for oral or oropharyngeal soft tissue defects were matched with patients who underwent pectoralis major myocutaneous flap reconstruction for similar defects. The 2 years of which the overall management costs according to the hospital perspective were calculated were divided into four periods: operative period, the postoperative phase, follow-up during first year and follow-up during second year after discharge. Results The total costs within the first 2 years were comparable at approximately 50,000 Euros. The lower costs of hospital admission (24 days versus 28 days; P = 0.005) in the postoperative phase outweighed the higher costs of the surgical procedure (692 min versus 462 min; P Conclusions Oral and oropharyngeal reconstruction with radial forearm flap is not more costly than pectoralis major flap reconstruction. Given the better functional outcome and the present cost analysis, reconstruction of oral and oropharyngeal defects is preferably performed using free tissue transfer.