Inter and intra-operator reliability of Lekholm and Zarb classification and proposal of a novel radiomic data-driven clustering for qualitative assessment of edentulous alveolar ridges.

OBJECTIVES: The present study was conducted to evaluate the reproducibility of Lekholm and Zarb classification system (L&Z) for bone quality assessment of edentulous alveolar ridges and to investigate the potential of a data-driven approach for bone quality classification. MATERIALS AND METHODS: Twenty-six expert clinicians were asked to classify 110 CBCT cross-sections according to L&Z classification (T0). The same evaluation was repeated after one month with the images put in a different order (T1). Intra- and inter-examiner agreement analyses were performed using Cohen's kappa coefficient (CK) and Fleiss' kappa coefficient (FK), respectively. Additionally, radiomic features extraction was performed from 3D edentulous ridge blocks derived from the same 110 CBCTs, and unsupervised clustering using 3 different clustering methods was used to identify patterns in the obtained data. RESULTS: Intra-examiner agreement between T0 and T1 was weak (CK 0.515). Inter-examiner agreement at both time points was minimal (FK at T0: 0.273; FK at T1: 0.243). The three different unsupervised clustering methods based on radiomic features aggregated the 110 CBCTs in three groups in the same way. CONCLUSIONS: The results showed low agreement among clinicians when using L&Z classification, indicating that the system may not be as reliable as previously thought. The present study suggests the possible application of a reproducible data-driven approach based on radiomics for the classification of edentulous alveolar ridges, with potential implications for improving clinical outcomes. Further research is needed to determine the clinical significance of these findings and to develop more standardized and accurate methods for assessing bone quality of edentulous alveolar ridges.

Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. METHODS: A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. RESULTS: The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. CONCLUSIONS: Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Diamond-Like Carbon Coating Reduces Connection Screw Head Stripping After Multiple Tightening Instances.

The stability of implant-abutment joint is fundamental for the long-term success of implant rehabilitation. The screw loosening, fracture, and head deformation are among the most common mechanical complications. Several surface treatments of titanium screws have been proposed to improve their resistance and stability. Diamond-like carbon (DLC) coating of the materials is widely used to increase their wear resistance and durability. The present study aimed to evaluate the effect of carbon fiber coating on the screw head on screw removal torque and screw head stripping. One hundred titanium implant screws were used, 50 without coating (Group 1) and 50 with DLC coating of the screw head (Group 2). Each screw was tightened with a torque of 25 Ncm and unscrewed 10 times. The removal torque was measured with a digital cap torque tester for each loosening. Optical 3d measurement of the screw head surface was performed by a fully automatic machine before and after multiple tightening to investigate surface modifications. The reverse torque values decreased with repeated tightening and loosening cycles in both groups without significant differences (P > .05). Optical measurements of surface dimensions revealed average changes of 0.0357 mm in Group 1 and 0.02312 mm in Group 2, which resulted to be statistically significant (P < .001). The DLC coating of the retention screw head can prevent its distortion and wear, especially after multiple tightening.

Can radiomic features extracted from intra-oral radiographs predict physiological bone remodelling around dental implants? A hypothesis-generating study.

AIM: The rate of physiological bone remodelling (PBR) occurring after implant placement has been associated with the later onset of progressive bone loss and peri-implantitis, leading to medium- and long-term implant therapy failure. It is still questionable, however, whether PBR is associated with specific bone characteristics. The aim of this study was to assess whether radiomic analysis could reveal not readily appreciable bone features useful for the prediction of PBR. MATERIALS AND METHODS: Radiomic features were extracted from the radiographs taken at implant placement (T0) using LifeX software. Because of the multi-centre design of the source study, ComBat harmonization was applied to the cohort. Different machine-learning models were trained on selected radiomic features to develop and internally validate algorithms capable of predicting high PBR. In addition, results of the algorithm were included in a multivariate analysis with other clinical variables (tissue thickness and depth of implant position) to test their independent correlation with PBR. RESULTS: Specific radiomic features extracted at T0 are associated with higher PBR around tissue-level implants after 3 months of unsubmerged healing (T1). In addition, taking advantage of machine-learning methods, a naive Bayes model was trained using radiomic features selected by fast correlation-based filter (FCBF), which showed the best performance in the prediction of PBR (AUC = 0.751, sensitivity = 66.0%, specificity = 68.4%, positive predictive value = 73.3%, negative predictive value = 60.5%). In addition, results of the whole model were included in a multivariate analysis with tissue thickness and depth of implant position, which were still found to be independently associated with PBR (p-value < .01). CONCLUSION: The combination of radiomics and machine-learning methods seems to be a promising approach for the early prediction of PBR. Such an innovative approach could be also used for the study of not readily disclosed bone characteristics, thus helping to explain not fully understood clinical phenomena. Although promising, the performance of the radiomic model should be improved in terms of specificity and sensitivity by further studies in this field.

Development and international validation of logistic regression and machine-learning models for the prediction of 10-year molar loss.

AIM: To develop and validate models based on logistic regression and artificial intelligence for prognostic prediction of molar survival in periodontally affected patients. MATERIALS AND METHODS: Clinical and radiographic data from four different centres across four continents (two in Europe, one in the United States, and one in China) including 515 patients and 3157 molars were collected and used to train and test different types of machine-learning algorithms for their prognostic ability of molar loss over 10 years. The following models were trained: logistic regression, support vector machine, K-nearest neighbours, decision tree, random forest, artificial neural network, gradient boosting, and naive Bayes. In addition, different models were aggregated by means of the ensembled stacking method. The primary outcome of the study was related to the prediction of overall molar loss (MLO) in patients after active periodontal treatment. RESULTS: The general performance in the external validation settings (aggregating three cohorts) revealed that the ensembled model, which combined neural network and logistic regression, showed the best performance among the different models for the prediction of MLO with an area under the curve (AUC) = 0.726. The neural network model showed the best AUC of 0.724 for the prediction of periodontitis-related molar loss. In addition, the ensembled model showed the best calibration performance. CONCLUSIONS: Through a multi-centre collaboration, both prognostic models for the prediction of molar loss were developed and externally validated. The ensembled model showed the best performance in terms of both discrimination and validation, and it is made freely available to clinicians for widespread use in clinical practice.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

BACKGROUND: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. METHODS: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. RESULTS: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. CONCLUSIONS: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

Prognostic significance of tumor budding thresholds in oral tongue squamous cell carcinoma.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. AIMS: The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. MATERIALS & METHODS: TB was evaluated on hematoxylin and eosin-stained sections in the hotspot area of the infiltrative front (×200-magnification). It was scored using a two-tier system, a three-tier system, and according to BD-model and revised-Grading system. Univariate and multivariate Cox regression analyses of disease-specific survival (DSS) and disease-free survival (DFS) were performed. A p < 0.05 was considered as statistically significant. RESULTS: The two-tier and three-tier systems resulted an independent prognostic factor of DSS. High-risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low-risk group. It is significantly increased even for intermediate-risk group. No significant differences emerged classifying patients according to BD-model and revised-Grading system. DISCUSSION: These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5-bud cutoff significantly discriminates their outcomes. CONCLUSION: Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

Cost/effectiveness analysis of treatment options for the rehabilitation of the total edentulous mandible.

BACKGROUND: Several solutions are available for the rehabilitation of edentulous jaws. Each treatment option is characterised by specific advantages and drawbacks. OBJECTIVE: The aim of this research was to perform a cost-effectiveness (CE) analysis of the main rehabilitative solutions of totally edentulous mandibles. METHODS: Decision tree models were built using TreeAge Pro Healthcare 2021 software to compare the following strategies: Conventional Denture (CD), Overdenture retained by two implants (OD-2), Overdenture retained by a bar on two implants (ODbar), Overdenture retained by 4 mini-implants (ODmini) and Fixed denture supported by 4 implants (FD). Costs were estimated using data from public rate tables. Effectiveness measures were obtained from a meta-analysis of literature data, normalising the different scales in 0-1 range. A value of 30 000€ per 1 normalised utility points was set as threshold of willingness to pay (WTP). Probabilistic sensitivity analysis (PSA) with 1000 Monte Carlo Simulations was performed to characterise uncertainty. RESULTS: Total costs ranged between 1804,40€ for CD and 10 008,80€ for FD rehabilitations, with an effectiveness of 0,69 and 0,95 normalised points (0-1 scale) for the two solutions. The ODbar resulted to be the most CE strategy at the established WTP value, with the highest Net Monetary Benefit (22 001,20€), followed by the OD-2 rehabilitation (21 866,80€). PSA analysis confirmed the dominance of OD-2 and ODbar strategies, confirming a net separation from the other alternatives. CONCLUSION: OD stabilised by 2 implants could represent a good rehabilitative solution for patients with edentulous mandible, being a good trade-off in terms of costs and effectiveness. Nevertheless, a standardised measure of oral health-related quality of life is needed to obtain more reliable results.

Impact of Circulating Cell-Free DNA (cfDNA) as a Biomarker of the Development and Evolution of Periodontitis.

In the last few decades, circulating cell-free DNA (cfDNA) has been shown to have an important role in cell apoptosis or necrosis, including in the development and evolution of several tumors and inflammatory diseases in humans. In this regard, periodontitis, a chronic inflammatory disease that can induce the destruction of supporting components of the teeth, could represent a chronic inflammatory stimulus linked to a various range of systemic inflammatory diseases. Recently, a possible correlation between periodontal disease and cfDNA has been shown, representing new important diagnostic-therapeutic perspectives. During the development of periodontitis, cfDNA is released in biological fluids such as blood, saliva, urine and other body fluids and represents an important index of inflammation. Due to the possibility of withdrawing some of these liquids in a non-invasive way, cfDNA could be used as a possible biomarker for periodontal disease. In addition, discovering a proportional relationship between cfDNA levels and the severity of periodontitis, expressed through the disease extent, could open the prospect of using cfDNA as a possible therapeutic target. The aim of this article is to report what researchers have discovered in recent years about circulating cfDNA in the development, evolution and therapy of periodontitis. The analyzed literature review shows that cfDNA has considerable potential as a diagnostic, therapeutic biomarker and therapeutic target in periodontal disease; however, further studies are needed for cfDNA to be used in clinical practice.

A Reciprocal Link between Oral, Gut Microbiota during Periodontitis: The Potential Role of Probiotics in Reducing Dysbiosis-Induced Inflammation.

Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome's functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.

Cast-free fabrication of a digital removable partial denture with a polyetheretherketone framework.

Digital workflows for removable partial dentures have enabled new machinable framework materials, including polyetheretherketone (PEEK). In addition, all denture components can be designed and manufactured digitally. Nonetheless, physical casts are still required for assembly of the components. The adoption of a cast-free fabrication procedure may enhance benefits, including a reduced number of procedures, faster processing, and reduced material waste. The purpose of this technical report was to demonstrate a workflow for the fabrication of a removable partial denture with a PEEK framework, milled teeth, and milled flanges, which uses intraoral scanning and no physical casts.

Intaglio surface trueness of milled and 3D-printed digital maxillary and mandibular dentures: A clinical study.

STATEMENT OF PROBLEM: While the dimensional accuracy of the intaglio surface of a removable complete denture is key to its adaptation, comfort, and clinical performance, information on the ability of milling and 3D-printing workflows to accurately reproduce this surface is lacking. PURPOSE: The purpose of this clinical study was to compare the trueness of the intaglio surface of milled and 3D-printed removable complete digital dentures. MATERIAL AND METHODS: Intraoral scans were obtained from 14 participants for a total of 20 edentulous arches. Ten maxillary and 10 mandibular denture bases were then designed and fabricated with a completely digital workflow, both with milling and 3D-printing. Fabricated dentures were digitized with the same intraoral scanner used to obtain intraoral digital scans of the edentulous arches. Standard tessellation language (STL) files of the printed and milled denture bases were used for 3D analysis and comparisons with the STL file of the corresponding designed denture base. Specifically, a reverse engineering software program was used to trim and extract intaglio surfaces, align them, and measure their global mean 3D distance. In order to evaluate the homogeneity of production accuracy of each manufacturing process, the intaglio surfaces were also divided into several regions of interest and the corresponding 3D distances measured. Within- and between-group differences and maxillary and mandibular dentures differences were assessed with parametric and nonparametric tests (α=.05). RESULTS: Milling showed a global better trueness of the entire intaglio surface (-0.002 mm) than 3D-printing (0.018 mm), both for the whole data set (P<.001) and for maxillary (P=.032) or mandibular (P=.049) denture base subgroups. Within each fabrication technology, maxillary (P<.11) and mandibular dentures (P=.2) showed no significant difference in trueness. Measured deviations were significantly different from zero for the 3D-printed dentures (P<.001), but not for the milled dentures (P=.487). Additionally, for milled dentures, no significant difference in trueness was found among the 11 regions of interest identified for the maxillary dentures (P=.085) and the 13 regions of interest for the mandibular dentures (P=.211). Conversely, 3D-printing showed significant variations in trueness among the same zones of interest, both in maxillary (P<.001) and mandibular (P=.004) dentures. CONCLUSIONS: Within the limits of the manufacturing methodologies used for complete dentures, milling can provide a slightly better trueness of the intaglio surface than 3D-printing, with less variation across several zones of interest. However, given the magnitude of such differences, they may be reasonably considered to be of limited, if any, clinical significance.

Accuracy of trial complete dentures fabricated by using fused deposition modeling 3-dimensional printing: An in vitro study.

STATEMENT OF PROBLEM: Three-dimensional (3D) printing technologies commonly used for trial complete dentures use photopolymerizing resins. Although effective, some clinical, process-related, and practical issues associated with them are still unclear. The option of using alternative printing technologies may help in overcoming limitations. PURPOSE: The purpose of this in vitro study was to evaluate the trueness of trial dentures fabricated by using 3D-printing fused deposition modeling (FDM). MATERIAL AND METHODS: Ten maxillary and 10 mandibular digital complete trial dentures designed from intraoral scans were fabricated from polylactic acid by using a FDM 3D-printer. Each denture was scanned, and the scans were compared with the digital file of the designed denture by means of a surface-matching software program. The mean distance (both signed and absolute) was measured and recorded for the intaglio surface, as well as for the entire denture surface. Statistical analysis was performed to investigate the significance of the extent of measured distances, as well as differences between intaglio and global deviations; subgroup analysis for arch type was also performed (α=.05). RESULTS: Mean values of the intaglio distance were not significantly different from zero (P=.223). The manufacturing accuracy of the intaglio surface was higher than that measured for the entire denture (P<.001), confirmed both by the averaged signed (0 mm and -0.028 mm, respectively) and the absolute mean deviations (0.06 mm and 0.08 mm, respectively). No significant differences were found between maxillary and mandibular trial dentures. CONCLUSIONS: 3D-printing may constitute a valid and practical option for accurate and affordable digital trial dentures.

Assessment of tooth displacement during the cast-free digital processing of milled dentures.

STATEMENT OF PROBLEM: Denture tooth displacement may have a significant impact on denture occlusion. This aspect has seldom been investigated, especially for digital denture processing techniques. PURPOSE: The purpose of this clinical study was to evaluate the accuracy of tooth position with milled digital dentures processed without physical casts. MATERIAL AND METHODS: Ten maxillary and 10 mandibular dentures designed from intraoral scans, milled, and processed without physical casts were investigated. The standard tessellation language (STL) files of the digitally designed dentures were compared with the scan of the dentures after processing (milling the denture base, milling teeth in a complete arch, and then bonding teeth into the base). The STL files were superimposed by using a surface-matching software program. After a preliminary alignment, the STL meshes were trimmed and reoriented; then, the final alignment was carried out by using the cameo surface. Six reference points (the mesiobuccal cusp on the most distal molar, the canine cusp, the middle of the incisal edge of the central incisor on both the left and the right side) were selected to measure tooth displacements along the X-, Y-, and Z-axes, corresponding (from the preliminary reorientation) to anteroposterior, mediolateral, and occlusal displacement, respectively. Tooth position accuracy was assessed by using median and interquartile range values. Univariate and multivariate statistical analyses were used to investigate the significance of the extent of displacements, as well as differences among displacement directions, reference teeth, side, and denture arch type (α=.05). RESULTS: Only the median (0.2 mm; interquartile range: 0.27 mm) occlusal displacement was significantly different from zero. A generalized estimated equation model addressing occlusal displacement as a dependent variable showed no significant effect of tooth type, side, or denture arch type, either alone or in combination. CONCLUSIONS: The tooth position of both maxillary and mandibular milled digital dentures processed without physical casts was accurate in the anteroposterior and mediolateral directions. Occlusal displacement seemed to be within the range of clinical acceptability; its consistency throughout the arch allowed optimization or compensation at the design or manufacturing step.

Three Dimensional Printed Surgical Guides: Effect of Time on Dimensional Stability.

PURPOSE: To analyze, in vitro, the dimensional stability over time of 3D-printed surgical guides. MATERIALS AND METHODS: Ten surgical guides, manufactured by digital light processing 3D-printing technology, were scanned immediately after post-processing and then after 5, 10, 15, and 20 days. The corresponding standard tessellation language (STL) files were used for comparison with the reference CAD project. Mean absolute deviation (MAD) of the intaglio surface, axial, and linear deviations of the sleeves' housings were measured. Generalized estimated equations models (α = 0.05) were used to investigate the effect of time. RESULTS: MAD of the teeth intaglio surface showed less variation (minimum: 0.002, maximum: 0.014 mm) than that of the mucosa (minimum: 0.026, maximum: 0.074 mm). Axial variations of the sleeves' housings on the sagittal (minimum: -0.008°, maximum: -0.577°) and frontal plane (minimum: -0.193°, maximum: 0.525°) changed with similar patterns, but opposite trends (decreasing for the former). Linear deviations of center points of the sleeves' housings had a shifting (minimum: -0.074, maximum: 0.02 mm) pattern with a decreasing tendency. Time after processing had a significant effect, either alone or nested with guides volume, on all outcomes of interest, except for MAD of the mucosa intaglio surface (p < 0.001), which was significantly affected only by the time-volume nested effect (p = 0.012). CONCLUSIONS: Within the limitations of the experimental design, postmanufacturing dimensional variations of surgical guides were statistically significant. Although limited, they are an additional source of variability affecting the overall accuracy of computer-guided surgery. As such, they should be addressed by further research.

Effects of Fermented Wheat Germ Extract on Oral Cancer Cells: An In Vitro Study.

Oral carcinoma is one of the most aggressive cancers, and despite the advances in the therapy, its mortality is still high. An attention in cancer treatment has focused on natural compounds due to their potential beneficial effects on human health. In this study, the effects of dietary supplement Fermented Wheat Germ Extract (FWGE) on oral tongue squamous cell carcinoma (OTSCC) cells were investigated In Vitro using three cell lines (HSC-3, SAS, SCC-25) with variable aggressiveness. The cell viability was significantly decreased by the treatment with high concentration of FWGE in every cell line. Regarding migration and invasion, HSC-3 and SCC-25 cells were most sensitive to FWGE since their movement was significantly reduced with 5 and 10 mg/ml FWGE, while SAS was inhibited only with 10 mg/ml FWGE. Chemotherapeutic compounds (cisplatin and 5-fluorouracil) significantly reduced all OTSCC cells viability. Importantly, combination of these drugs with 10 mg/ml FWGE significantly decreased the cell viability compared to the treatment with the chemotherapeutics or FWGE alone. Based on these In Vitro experiments, the use of FWGE seems to improve the anticancer effects on OTSCC cells. Further In Vivo and clinical studies should be conducted to verify the positive effects of FWGE for OTSCC patients.

Pre-treatment neutrophil-to-lymphocyte ratio is an independent prognostic factor in head and neck squamous cell carcinoma: Meta-analysis and trial sequential analysis.

Inflammation seems to play a critical role in the development and progression of different cancers. Neutrophil-to-lymphocyte ratio (NLR) is an easily measurable marker of systemic inflammation. The purpose of this systematic review and meta-analysis was to evaluate the prognostic role of the pre-treatment NLR, in terms of overall survival (OS) and disease-free survival (DFS), in patients with primary head and neck squamous cell carcinoma (HNSCC) treated by surgery alone or followed by chemo/radiotherapy. This systematic review was performed according to the guidelines reported in the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Meta-analysis of OS and DFS was performed using the inverse of variance test. Fixed-effect models were used on the basis of the presence of heterogeneity. Risk of bias assessment and trial sequential analysis (TSA) were also performed; the quality of the evidence was evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The analysis revealed that a higher value of pre-treatment NLR correlates with a statistically significant decrease of OS (HR, 1.56; 95% CI: [1.35, 1.80]; p < 0.00001) and a lower DFS (HR, 1.64; 95% CI: [1.30, 2.07]; p < 0.0001) in HNSCC patients.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer.

BACKGROUND: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. METHODS: Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. RESULTS: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . CONCLUSION: The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.