Clinical insights into traumatic injury of the inferior alveolar and lingual nerves: a comprehensive approach from diagnosis to therapeutic interventions.

OBJECTIVES: This scoping review explores the risk and management of traumatic injuries to the inferior alveolar and lingual nerves during mandibular dental procedures. Emphasizing the significance of diagnostic tools, the review amalgamates existing knowledge to offer a comprehensive overview. MATERIALS AND METHODS: A literature search across PubMed, Embase, and Cochrane Library informed the analysis. RESULTS: Traumatic injuries often lead to hypo-/anesthesia and neuropathic pain, impacting individuals psychologically and socially. Diagnosis involves thorough anamnesis, clinical-neurological evaluations, and radiographic imaging. Severity varies, allowing for conservative or surgical interventions. Immediate action is recommended for reversible causes, while surgical therapies like decompression, readaptation, or reconstruction yield favorable outcomes. Conservative management, utilizing topical anesthesia, capsaicin, and systemic medications (tricyclic antidepressants, antipsychotics, and serotonin-norepinephrine-reuptake-inhibitors), proves effective for neuropathic pain. CONCLUSIONS: Traumatic nerve injuries, though common in dental surgery, often go unrecorded. Despite lacking a definitive diagnostic gold standard, a meticulous examination of the injury and subsequent impairments is crucial. CLINICAL RELEVANCE: Tailoring treatment to each case's characteristics is essential, recognizing the absence of a universal solution. This approach aims to optimize outcomes, restore functionality, and improve the quality of life for affected individuals.

The Magic Triangle in Oral Potentially Malignant Disorders: Vitamin D, Vitamin D Receptor, and Malignancy.

OPMDs (oral potentially malignant disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of various diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also suggest a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD and investigate their potential association and ramifications for clinical management of OPMDs.

The Sympathetic Nervous System in Dental Implantology.

The sympathetic nervous system plays a vital role in various regulatory mechanisms. These include the well-known fight-or-flight response but also, for example, the processing of external stressors. In addition to many other tissues, the sympathetic nervous system influences bone metabolism. This effect could be highly relevant concerning osseointegration, which is responsible for the long-term success of dental implants. Accordingly, this review aims to summarize the current literature on this topic and to reveal future research perspectives. One in vitro study showed differences in mRNA expression of adrenoceptors cultured on implant surfaces. In vivo, sympathectomy impaired osseointegration in mice, while electrical stimulation of the sympathetic nerves promoted it. As expected, the beta-blocker propranolol improves histological implant parameters and micro-CT measurements. Overall, the present data are considered heterogeneous. However, the available publications reveal the potential for future research and development in dental implantology, which helps to introduce new therapeutic strategies and identify risk factors for dental implant failure.

Hard and soft tissue regeneration of severe peri-implantitis defects with the laser-assisted peri-implant defect regeneration technique: 3-year results.

PURPOSE: This retrospective cohort study evaluates the regeneration of severe peri-implantitis deficiencies treated with the laser-assisted peri-implant defect regeneration (LAPIDER) approach within a 3-year follow-up. METHODS: Twenty-four implants with severe peri-implantitis in 18 patients were treated according to the LAPIDER technique. In contrast to classic techniques for reconstructive peri-implantitis surgery with a marginal incision, a buccal split-flap preparation avoiding papillae separation was used. After a coronal flap elevation and a laser-assisted peri-implant defect cleaning, connective tissue and autogenous bone grafting was performed. Primary outcomes were the changes of the marginal bone levels (MBL) and the buccal bone thickness. Secondary outcomes included implant survival, peri-implant probing depths (PPD), bleeding on probing (BOP), recession, width of keratinized mucosa (KMW), thickness of keratinized mucosa (KMT), soft tissue esthetics (PES), and implant success. RESULTS: MBL improved interproximal by 3.10 ± 2.02 mm (p < 0.001), buccal by 3.49 ± 2.89 mm (p < 0.001), and lingual by 1.46 ± 1.98 mm (p = 0.003); buccal bone thickness by 0.55 ± 0.60 mm (p = 0.005), and 1.01 ± 1.25 mm (p = 0.001) at 1 and 3 mm below reference level. Two implants were removed; 22 implants were still in function at a mean follow-up of 36 months. PPD changed from 5.05 ± 1.39 to 3.08 ± 0.71 mm (p < 0.001); recession was reduced from 2.07 ± 1.70 to 0.91 ± 1.13 mm (p = 0.001); KMW increased from 2.91 ± 1.81 to 4.18 ± 1.67 mm (p = 0.006); KMT improved from 1.73 ± 0.50 to 2.44 ± 0.43 mm (p < 0.001); PES changed from 7.7 ± 2.8 to 10.7 ± 1.9 (p < 0.001). 45.8% to 54.2% of the implants met the criteria of implant success. CONCLUSIONS: The favorable results document the proof of principle for the regeneration of severe peri-implant hard and soft tissue deficiencies by the LAPIDER treatment approach.

Surgical safety checklists for dental implant surgeries-a scoping review.

OBJECTIVES: In both elective surgeries and aviation, a reduction of complications can be expected by paying attention to the so-called human factors. Checklists are a well-known way to overcome some of these problems. We aimed to evaluate the current evidence regarding the use of checklists in implant dentistry. METHODS: An electronic literature search was conducted in the following databases: CINHAL, Medline, Web of Science, and Cochrane Library until March 2022. Based on the results and additional literature, a preliminary checklist for surgical implant therapy was designed. RESULTS: Three publications dealing with dental implants and checklists were identified. One dealt with the use of a checklist in implant dentistry and was described as a quality assessment study. The remaining two studies offered suggestions for checklists based on literature research and expert opinion. CONCLUSIONS: Based on our results, the evidence for the use of checklists in dental implantology is extremely low. Considering the great potential, it can be stated that there is a need to catch up. While creating a new implant checklist, we took care of meeting the criteria for high-quality checklists. Future controlled studies will help to place it on a broad foundation. CLINICAL RELEVANCE: Checklists are a well-known way to prevent complications. They are especially established in aviation, but many surgical specialties and anesthesia adopt this successful concept. As implantology has become one of the fastest-growing areas of dentistry, it is imperative that checklists become an integral part of it.

Diagnostic tests for titanium hypersensitivity in implant dentistry: a systematic review of the literature.

PURPOSE: There are rising concerns about titanium hypersensitivity reaction regarding dental endosseous implants. This review aims to summarize and compare the validity and reliability of the available dermatological and laboratory diagnostic tests regarding titanium hypersensitivity. The following PICO design was used: In Patients with titanium dental implants (P) does epicutaneous testing (ECT) (I), compared to lymphocyte transformation test (LTT) or Memory Lymphocyte Immunostimulation Assay (MELISA) (C) detect hypersensitivity reactions (O)? A literature search was performed including all studies dealing with this topic. Studies regarding orthopedic implants were excluded. METHODS: Three databases (MEDLINE PubMed, Cochrane Library, SciELO) were screened for suitable studies and an additional manual search was also performed. Literature regarding hypersensitivity reactions in orthopedic implants, hypersensitivity reactions regarding implants not related to dental or maxillofacial surgery, animal studies and in vitro studies were excluded. A quality assessment of all selected full-text articles was performed. Randomized, controlled trials were evaluated with the Cochrane Risk of Bias Tool I. Cohort studies were assessed according to the New Castle-Ottawa Scale and case series according to Moga et al. (Development of a quality appraisal tool for case series studies using a modified Delphi technique. 2012). RESULTS: 10 studies were included in the quantitative synthesis and available for the endpoint diagnostics of intolerance reactions to titanium dental implants: 2 clinical studies, 7 cohort studies and 1 case series. The potential for bias (internal validity) for these studies was overall rated as high. CONCLUSIONS: The study of the available literature regarding ECT and MELISA or LTT in patients with suspected titanium hypersensitivity showed inconsistent results in terms of reliability and validity and thus, those tests should be regarded cautiously. There is strong evidence that titanium hypersensitivity in dental implants is associated with innate immunity: unspecific pro-inflammatory responses due to particle induced hyperreactivity of macrophages or toxicological responses especially towards nanoparticles rather than activation of the adaptive immune system. Therefore, tests detecting allergies do not seem expedient and inflammatory clinical signs should be regarded as leading parameters.

Dental implants in patients with head and neck cancer-A systematic review and meta-analysis of the influence of radiotherapy on implant survival.

PURPOSE: The purpose of this meta-analysis was to compare implant survival in irradiated and non-irradiated bone and to investigate potential risk factors for implant therapy in oral cancer patients. MATERIAL AND METHODS: An extensive search in the electronic databases of the National Library of Medicine was performed. Systematic review and meta-analysis were conducted according to PRISMA statement. The meta-analysis was performed for studies with a mean follow-up of at least three and five years, respectively. RESULTS: The systematic review resulted in a mean overall implant survival of 87.8% (34%-100%). The meta-analysis revealed a significantly higher rate of implant failure in irradiated bone compared to non-irradiated bone (p < .00001, OR 1.97, CI [1.63, 2.37]). The studies also showed that implants placed into irradiated grafted bone were more likely to fail than those in irradiated native bone (p < .0001, OR 2.26, CI [1.50, 3.40]). CONCLUSION: Even though overall implant survival was high, radiotherapy proves to be a significant risk factor for implant loss. Augmentation procedures may also increase the risk of an adverse outcome, especially in combination with radiotherapy. CLINICAL RELEVANCE: The treatment of patients receiving radiotherapy of any form requires precise individual planning and a close aftercare. Implants should be placed in local bone rather than in bone grafts, if possible.

Importance of keratinized mucosa around dental implants: Consensus report of group 1 of the DGI/SEPA/Osteology Workshop.

OBJECTIVES: To assess the literature on (i) the relevance of the presence of a minimum dimension of keratinized peri-implant mucosa (KPIM) to maintain the health and stability of peri-implant tissues, and; (ii) the surgical interventions and grafting materials used for augmenting the dimensions of the KPIM when there is a minimal amount or absence of it. MATERIAL & METHODS: Two systematic reviews complemented by expert opinion from workshop group participants served as the basis of the consensus statements, implications for clinical practice and future research, and were approved in plenary session by all workshop participants. RESULTS: Thirty-four consensus statements, eight implications for clinical practice, and 13 implications for future research were discussed and agreed upon. There is no consistent data on the incidence of peri-implant mucositis relative to the presence or absence of KPIM. However, reduced KPIM width is associated with increased biofilm accumulation, soft-tissue inflammation, greater patient discomfort, mucosal recession, marginal bone loss and an increased prevalence of peri-implantitis. Free gingival autogenous grafts were considered the standard of care surgical intervention to effectively increase the width of KPIM. However, substitutes of xenogeneic origin may be an alternative to autogenous tissues, since similar results when compared to connective tissue grafts were reported. CONCLUSION: Presence of a minimum width of KPIM should be assessed routinely in patients with implant supported restorations, and when associated with pathological changes in the peri-implant mucosa, its dimensions may be surgically increased using autogenous grafts or soft-tissue substitutes with evidence of proven efficacy.

Oral Squamous Cell Carcinomas Developing from Oral Lichen Planus: A 5-21 year Retrospective Study.

Background and Aims: There is insufficient data regarding clinical characteristics, relapse rates, as well as lymph node metastasis of squamous cell carcinomas of the oral cavity (OSCC) developing from oral lichen planus (OLP-OSCC). The aim of this retrospective study was to evaluate clinical characteristics, as well as relapse, recurrence and survival rates of OLP-OSCC. Methods: In a retrospective monocenter analysis, all consecutive patients with an OSCC treated in the time period 1st January 2000-December 31 2016 were reviewed. All patients with OSCC developing from OLP/OLL (oral lichenoid lesions) were identified and analyzed for epidemiological data, risk profile, location of primary tumor, pTNM classification, lymph node metastasis, primary therapy, recurrence, and outcome. Results: A total of 103 patients (45%♂/ 55%♀) with an average age of 62 ± 14 year were included in this study. At the time of initial diagnosis, 17% (n = 18) of patients had cervical metastases (CM) whereas only 11% (11 patients) displayed advanced tumor sizes (T > 2). T-status (p = 0.003) and histopathological grading (p = 0.001) had an impact on the incidence of CM. 39.6% of the patients developed a relapse after an average of 24 months with a mean of two recurrences per patient. Advanced tumor size had a significant impact on the 5 year overall survival and was associated with disease-free survival of the patients (p < 0.001, respectively p = 0.004). Conclusion: Although initial lymph node metastases were not more frequent, more aggressive recurrence patterns compared to OSCC were seen for OLP-OSCC. Therefore, based on the study results, a modified recall for these patients is suggested.

Buccal Bone Thickness in Anterior and Posterior Teeth-A Systematic Review.

(1) Background: Immediate dental implant placement has been a subject of great interest over the last decade. Here, information regarding the anatomy and bone thickness of the jaw prior to dental implant placement is crucial to increase the surgery's success and the patient's safety. The clinical premises for this approach have been controversially discussed. One of those heavily discussed premises is a buccal bone thickness of at least 1 mm thickness. This meta-analysis aims to systematically review buccal bone thickness (BBT) in healthy patients. Thus, the feasibility of immediate dental implant placement in daily practice can be assessed. (2) Methods: A search in the electronic databases was performed to identify articles reporting on BBT that was measured by computed tomography in adults. (3) Results: We were able to find 45 studies, including 4324 patients with 25,452 analyzed teeth. The analysis showed a BBT at the alveolar crest of 0.76 ± 0.49 mm in the maxillary frontal and of 1.42 ± 0.74 mm in the maxillary posterior region. In the mandible, the average measured values were similar to those in the maxilla (front: 0.95 ± 0.58 mm; posterior: 1.20 ± 0.96 mm). In the maxillary frontal region 74.4% and in the mandibular frontal region 61.2% of the crestal buccal bones showed widths <1 mm. (4) Conclusions: In more than 60% of the cases, the BBT at the alveolar crest is <1 mm in maxillary and mandibular frontal regions. This anatomic data supports careful pre-surgical assessment, planning of a buccal graft, and critical selection of indication for immediate implant placement, especially in the maxillary and mandibular frontal and premolar region.

Clinical long-term and patient-reported outcomes of dental implants in oral cancer patients.

BACKGROUND AND PURPOSE: The aim of this clinical study was to investigate the clinical long-term and patient-reported outcome of dental implants in patients with oral cancer. In addition, analysis of the influence of radiation therapy, timing of implant insertion, and augmentation procedures on implant survival was performed. MATERIAL AND METHODS: This retrospective study investigated the clinical outcome of 711 dental implants in 164 oral cancer patients, inserted by experienced surgeons of the Department of Oral and Maxillofacial Surgery, University Medical Center Mainz, Germany. Oral health-related quality of life (OHRQoL) was evaluated. RESULTS: Cumulative 5-year and 10-year implant survival rates for all included implants were 87.3% and 80.0%. Implants placed straight after ablative surgery (primary implant placement) and implants placed after completing the oncologic treatment (secondary implant placement) showed a comparable implant survival (92.5% vs. 89.5%; p = 0.635). Irradiation therapy had no significant influence on implant survival of secondary placed implants (p = 0.929). However, regarding implant site (native bone vs. augmented bone) and radiation therapy (non-irradiated bone vs. irradiated bone), implants inserted in irradiated bone that received augmentation procedures showed a statistically significant lower implant survival (p < 0.001). Patients reported a distinct improvement in OHRQoL. CONCLUSIONS: Promising long-term survival rates of dental implants in patients after treatment of oral cancer were seen. In addition, patients benefit in form of an improved OHRQoL. However, bone augmentation procedures in irradiated bone may result in an impaired implants' prognosis.

A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone.

BACKGROUND: The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo. METHODS: Eight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with ("+";n = 20) and without ("-";n = 20) collagen membrane was applied. Blood and bone was collected 24, 72 h, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points. RESULTS: Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in "+" group when compared to "-" (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in "+" (all p < 0.05). Fourteen days after surgery, the significant highest values for all bone turnover markers were detected in "-" (all p < 0.05). A significant difference in favor of group "-" could also be detected after 3 weeks in terms of both acid phosphatases (p < 0.05). In histology, no significant differences could be detected. CONCLUSION: Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.

Biofunctionalization of porcine-derived collagen matrices with platelet rich fibrin: influence on angiogenesis in vitro and in vivo.

OBJECTIVES: Porcine-derived collagen matrices (CM) can be used for oral tissue regeneration, but sufficient revascularization is crucial. The aim of this study was to analyze the influence of platelet-rich fibrin (PRF) on angiogenesis of different CM in vitro and in vivo. MATERIALS AND METHODS: Three different CM (mucoderm®, jason®, collprotect®) were combined with PRF in a plotting process. Growth factor release (VEGF, TGF-ß) was measured in vitro via ELISA quantification after 1,4 and 7 days in comparison to PRF alone. In ovo yolk sac (YSM) and chorion allantois membrane (CAM) model, angiogenic potential were analyzed in vivo with light- and intravital fluorescence microscopy after 24 h, then verified with immunohistochemical staining for CD105 and αSMA. RESULTS: Highest growth factor release was seen after 24 h for all three activated membranes in comparison to the native CM (VEGF 24 h: each p < 0.05; TGF-ß: each p < 0.001) and the PRF (no significant difference). All activated membranes revealed a significantly increased angiogenic potential in vivo after 24 h (vessels per mm2: each p < 0.05; branching points per mm2: each p < 0.01; vessel density: each p < 0.05) and with immunohistochemical staining for CD105 (each p < 0.01) and αSMA (each p < 0.05). CONCLUSIONS: PRF improved the angiogenesis of CM in vitro and in vivo. CLINICAL RELEVANCE: Bio-functionalization of CM with PRF could easily implemented in the clinical pathway and may lead to advanced soft tissue healing.

The risk of tooth root injuries using cortical screws for intermaxillary fixation and osteosynthesis plates - A retrospective analysis.

Intermaxillary fixation (IMF) and osteosynthesis plates (OP) are widely used for the non-surgical and surgical treatment of mandible and condyle fractures. The aim of this retrospective study was to analyze the frequency of tooth root injuries by IMF and OP screws. Electronic patient reports (2004-2013) were screened for patients treated with either IMF screws and/or OP in the Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Germany. The frequency and the position of endangered and injured teeth were analyzed by orthopantomogram (OPTG) and cone beam computer tomography (CBCT). Next, possible predictive factors for tooth root injuries, namely interdental- and crestal distance, screw length and distance between tooth root and screw were evaluated. Further, the accuracy of OPTG vs. CBCT concerning the diagnosis of tooth root injuries was analyzed. Three-hundred sixty-six patients were included and 3388 teeth were defined as endangered by IMF- and OP screws. Overall, 16 injured teeth (0.5%) in 13 patients (3.55%) were detected. Nine injuries (56.3%) were caused by IMF- and seven injuries (43.8%) by OP screws. Three teeth were non-vital, one tooth had to be extracted. No correlation between the predictive factors crestal distance, screw length and tooth root injuries was found. If tooth injury occurred, a significant correlation between the interdental distance and the distance between tooth root and screw was found (κ = 0.48; p < 0,0001). Comparison between OPTG vs. CBCT demonstrated that many of the injuries that were seen in the OPTG (n = 230) could not be verified in the CBCT scans (n = 16) (κ = 0.12). To conclude, screws for IMF and OP can be considered as a safe procedure concerning the risk of tooth root injuries.

Postgraduate training in Oral- and Maxillofacial Surgery: Results of a survey among 74 German interns.

The aim of this study was to asses a survey of residents to obtain relevant information about their current situation in training in Oral and Maxillofacial Surgery in Germany. Special focus was given to the personal and clinical preferences of the residents, their main subjects of interest and plans after residency. Furthermore, the different principles of education at German teaching hospitals were evaluated. Overall, 74 questionnaires were completed on a voluntary and anonymous basis by German residents for Oral and Maxillofacial Surgery. Participants' mean age was 32.74 years (68% male, 27% female). Most participants were in the fifth year of training (32%) and members of the German Association of Oral and Maxillofacial Surgery (70%). This rate increased with progress in residency (p = 0.006). Most residents (70%) were employed at university hospitals, followed by non-university hospitals (26%) and private practices (4%). Residents from university hospitals (3.06 ± 0.39 years) were less advanced in training compared to residents from non-university hospitals and private practices (4.10 ± 0.54 years; p = 0.005). Part-time employed residents were significantly younger (30.64 ± 2.37 years) than full-time employed residents (33.25 ± 0.64 years, p = 0.002). Structured concepts of training existed in 64% of the hospitals, while training depending on the current year of residency (42%) was most common. Most of the residents would prefer a systematic rotation system (59%). Main subjects of clinical interest were aesthetic (50%) and orthognathic surgery (46%). The interest in dento-alveolar surgery (34%) significantly increased with participants' age (p = 0.008). Clefts and malformations were favoured by few residents (16%). Most participants planned to specialize in facial plastic surgery after residency (76%). The data collected might give evidence for an increasing importance of structured training concepts in Oral and Maxillofacial Surgery. It might be relevant to enhance the interest and the excitement of residents for oncology, traumatology, cleft and malformation surgery.

Early cell response of osteogenic cells on differently modified implant surfaces: Sequences of cell proliferation, adherence and differentiation.

OBJECTIVES: Osseointegration of dental implants is a crucial prerequisite for long-term survival. Therefore, surface modifications are needed to interact with the extracellular environment and to trigger osteogenic cell responses such as cell proliferation, adherence, and differentiation. The purpose of this study was to investigate different surface modifications in vitro over 2 weeks. MATERIALS AND METHODS: Commercially available cells from a human osteogenic cell line (HHOB-c) were cultivated on the following surfaces: titanium with smooth surfaces (polished titanium (P), machined titanium (M), polyetheretherketone (Peek)), titanium with rough and hydrophilised surfaces (acid etched titanium (A), sandblasted acid etched titanium (SA and SA2), sandblasted acid etched hydrophilised (SAH), titanium plasma painted titanium (TPS)), titanium with calcium phosphate-containing surfaces (titanium plasma painted calcium phosphate modified titanium (TPS-CaP), sandblasted calcium phosphate modified titanium (S-CaP), sandblasted acid etched calcium phosphate modified titanium (SA-CaP)), and zirconium-oxide (yttrium amplified zirconium (Z), yttrium amplified Ca2+ delivering zirconium (Z-Ca)). Tissue culture polystyrene (TCPS) served as a control. Cell count was assessed after 24 h, 48 h, 72 h, 7 d, and 14 d; osteogenic cell adherence and differentiation were analysed by using cellular Quantitative Immuno-Cytochemistry (QIC) assay for alkaline phosphatase (AP), osteocalcin (OC), integrin alpha V (ITGAV), and talin (T). RESULTS: All tested surfaces showed a positive influence on the differentiation and adherence of osteogenic cells, especially P, M, A, TCPS, and Peek. After 48 h, the surfaces M, SA and SAH had induced a positive influence on adherence, whereas SA2, SA, and SAH triggered proliferation after 14 d. CONCLUSIONS: Rough and hydrophilised surface modifications, such as SAH, trigger osteogenic cell responses. These in vitro results highlight the potential use of SAH surface modifications of dental implants and indicate further clinical studies are warranted.

Proinflammatory cytokines as serum biomarker in oral carcinoma-A prospective multi-biomarker approach.

BACKGROUND: Inflammation and cell-mediated immunity have a key role in different stages of carcinogenesis. The aim of this prospective study was to assess serum levels of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-α), and MHC class I polypeptide-related sequence B (MICB) in patients with oral premalignant lesion (OPL), oral squamous cell carcinoma (OSCC), and healthy controls in a multi-biomarker approach as a potential diagnostic and prognostic tool for OSCC. MATERIAL AND METHODS: A total of 205 patients (81 with OSCC, 75 with OPL, and 49 healthy controls) were included in this prospective study. Cytokine concentrations were measured by commercial enzyme linked immunoassay and chemiluminescence immunoassay. RESULTS: IL-6, IL-8, and sIL-2R were significantly elevated in OSCC patients compared to healthy controls and to OPL patients. Higher T-Grade (>T2) and positive lymph node involvement resulted in significantly higher IL-6 values (P < .001 and P = .037). IL-6 serum values ≥5 pg/mL (n = 45) and sIL-2R serum values ≥623 U/mL (n = 19) indicated a significant lower survival rate compared to OSCC patients with low IL-6 (n = 36) and sIL-2R values (n = 62, P = .023 and P = .026). ROC and classification tree analyses identified the combination of IL-6 and IL-8 as diagnostic markers with good diagnostic accuracy. CONCLUSION: In conclusion, IL-6, IL-8, and sIL-2R are strongly associated with OSCC oncogenesis and IL-6 and sIL-2R seem to be promising and potent biomarkers for evaluating patients' prognosis.

Hemoglobin, C-reactive protein and ferritin in patients with oral carcinoma and their clinical significance - A prospective clinical study.

AIM: For oral squamous cell carcinoma (OSCC), biomarkers are much in need to predict prognosis and to overcome possible resistance mechanisms to adjuvant therapies. The aim of this study was to evaluate serum level of hemoglobin, C-reactive protein (CRP) and ferritin as possible liquid biopsy to predict survival, metastasis and tumor relapse of OSCC. MATERIAL AND METHODS: A prospective clinical study was conducted. Overall, serum levels of hemoglobin, CRP and ferritin in 82 OSCC patients and 63 controls were preoperatively investigated. RESULTS: Patients with an anemia showed a significant lower survival than patients with no anemia preoperative. Patients with T3/T4 cancer had significant lower hemoglobin values (p = 0.002). CRP and ferritin were statistically overexpressed in late tumor stages T3/T4 (ferritin: p = 0.045, CRP: p < 0.05) compared to control. Log Rank testing indicated a statistical correlation of up regulated ferritin levels with local tumor recurrence (p = 0.012) and local lymph node metastasis (p = 0.008). CONCLUSION: Presented biomarker CRP, ferritin and hemoglobin may serve as a liquid biopsy for prediction of OSCC especially for larger tumor sizes, overall survival and tumor relapse and demand a more radical therapy approach.

The matrix metalloproteinase and insulin-like growth factor system in oral cancer - a prospective clinical study.

AIM: The absence of reliable single serum biomarkers for oral premalignant lesion (OPL) and oral squamous cell carcinoma (OSCC) limits early diagnosis, monitoring of advanced disease, and prediction of prognosis. METHODS: In this prospective study, serum levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-13, insulin-like growth factor (IGF)-1, and IGF-binding protein (IGFBP)-3 were measured in 81 untreated OSCC patients, 49 healthy subjects, and 75 individuals with OPLs, and correlated with clinicopathological parameters. RESULTS: Serum levels of MMP-3 were significantly higher in OSCC patients compared to healthy subjects (p=0.004). Mean IGF-1 and IGFBP-3 levels in OSCC patients were significantly lower in healthy subjects (p=0.001 and p<0.001). OSCC patients with an IGF-1 serum value <130 ng/mL (median) showed a significantly lower survival rate compared to ≥130 ng/mL (p=0.049). Combined use of IGF-1 (<130 ng/mL) and IGFBP-3 (<3.1 µg/mL) resulted in a significantly lower 12-month cumulative survival compared to the complementary set (78.5% vs 93.8%; p=0.031). There was a significantly positive correlation between IGF-1 and IGFBP-3 serum values (rs =0.625, p<0.001). CONCLUSION: This study shows that IGF-1 and IGFBP-3 have a vital role in the pathogenesis of OSCC and indicates for the first time that IGF-1 and IGFBP-3 in combination may be applied as potential tools for prognosis of OSCC.

Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature.

Oral squamous cell carcinoma (OSCC) represents the sixth most common cancer, accounting for 2-4% of all malignancies worldwide. The overall survival rate of less than 60% remains generally poor, with prognosis heavily relying on the TNM staging system. Tumor size as well as the presence and extent of lymph node metastases are widely recognized as the most important predictors. However, the underlying mechanisms that lead to an aggressive phenotype are not yet fully understood. Therefore, possible biomarkers are much in need to predict prognosis, to help individualize therapy approaches, and to overcome possible resistance mechanisms. Despite a multitude of recently published biomarkers for OSCC, there is still an ongoing debate regarding their implementation in the clinical workflow. Thus, a systematic literature search via PubMed was performed to update the current literature with the latest evidence. In total, 128 studies were included and over 100 different biomarkers evaluated with reference to their influence of survival, tumor recurrence, advanced grading and lymph node metastasis. In this review, we highlight the important molecular mechanism underlying possible markers in tissue, blood or saliva samples for OSCC. As a major result, no clinical trials could be obtained to prove clinical importance of the validated predictors for survival, tumor recurrence, lymph node metastasis and therapy resistance. Therefore, further clinical investigations are much needed.