Search

To evaluate the advantages of dual-energy computed tomography (DECT) virtual non-hydroxyapatite color mapping (VNHAP) in combination with standard bone CT (BCT) in the identification of subtle or occult traumatic fractures referred to emergency and acceptance departments (DEAs). Forty patients (22 men; mean age 83 ± 23.7 y) with suspected traumatic fractures referred to our emergency department and examined with a fast kilovoltage-switching single-source spectral CT scan between January and October 2023 were retrospectively reviewed. The BCT and VNHAP images were blindly evaluated by two radiologists with >10 years and <2 years of experience in musculoskeletal imaging. Both techniques were evaluated in terms of sensitivity (SE), specificity (SP), positive and negative predictive values (PPVs and NPVs) and accuracy for fracture detection, as confirmed at a 3-month clinical–instrumental follow-up. Inter-observer agreement and examination times were also analyzed. Fractures were confirmed in 18/40 cases. The highest values of diagnostic performance for VNHAP images were obtained in terms of SP (90.9% and 95%) and PPV (87.5% and 92.8%) and for the less experienced operator. No statistically significant differences were observed between the diagnostic accuracy of the two readers in the evaluation of VNHAP images. Inter-observer agreement was moderate (κ = 0.536) for BCT and substantial (κ = 0.680) for VNHAP. Comparing the two operators, a significantly longer examination time for BCT and no significant difference for VNHAP were registered. Our preliminary experience may encourage the employment of VNHAP maps in combination with BCT images in emergency settings. Their use could be time-saving and valuable in terms of diagnostic performance, especially for less experienced operators. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody‐drug conjugate (ADC) therapy. Methods: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT‐PCR, Western Blot analysis, and ELISA. Results: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer‐derived extracellular vesicles. Moreover, LGALS3BP high‐expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC‐payload DM4, with an IC50 around 0.3 nM. Conclusions: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC‐based therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Periodontitis is a multifactorial and infective oral disease that leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, exploring new therapeutic strategies for a personalized approach is urgent. For this reason, the aim of this study is to summarize recent advances and the potential of oxidative stress biomarkers in the early diagnosis and personalized therapeutic approaches in periodontitis. Recently, ROS metabolisms (ROMs) have been studied in the physiopathology of periodontitis. Different studies show that ROS plays a crucial role in periodontitis. In this regard, the reactive oxygen metabolites (ROMs) started to be searched for the measures of the oxidizing capacity of the plasma understood as the total content of oxygen free radicals (ROS). The oxidizing capacity of plasma is a significant indicator of the body's oxidant state as well as homocysteine (Hcy), sulfur amino acid, which has pro-oxidant effects as it favors the production of superoxide anion. More specifically, the thioredoxin (TRX) and peroxiredoxin (PRX) systems control reactive oxygen species (ROS), such as superoxide and hydroxyl species, to transduce redox signals and change the activities of antioxidant enzymes to remove free radicals. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), among other antioxidant enzymes, change their activity when ROS are produced in order to neutralize free radicals. The TRX system is triggered and transduces redox signals to do this. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm. [ABSTRACT FROM AUTHOR]

Introduction: The number of patients with metastatic castration-resistant prostate cancer (mCRPC) is expected to increase due to the long life expectancy of those with advanced disease who are also more commonly diagnosed today because of stage migration. Several compounds are available for treating these patients.Areas Covered: We reviewed currently available treatments for mCRPC, their mechanism of action and resistance, and we explored possible predictors of treatment success useful to predict survival in mCRPC patients.Expert Opinion: A combination of molecular, clinical, pathological, and imaging features is necessary to correctly estimate patients' risk of death. The combination of these biomarkers may allow clinicians to tailor treatments based on cancer history and patients' features. The search of predictive biomarkers remains an unmet medical need for most patients with mCRPC. [ABSTRACT FROM AUTHOR]

Simple Summary: The results of tumor budding are an independent prognostic factor of locoregional recurrences in many solid cancers, including colorectal, nasopharyngeal, esophageal, and lung cancer. Regarding oral squamous cell carcinoma, tumor budding predicts poor survival outcomes regardless of the tumor subsite and the pathological stage. Several detection methods for tumor budding have been proposed in the literature in order to reach an agreement on a standardized scoring system. However, the lack of a standardized assessment method prevents its evaluation in a multidisciplinary setting. In this context, this study aims to critically review the literature data regarding the prognostic role of tumor budding in oral squamous cell carcinoma. The validation of a tumor budding detection method based on tumor stage and site could be relevant to improving risk stratification and planning the clinical management of patients. Moreover, tumor budding could be included in daily pathological practice to better predict the patient's outcomes. Tumor Budding (TB) represents a single cancer cell or a small cluster of less than five cancer cells on the infiltrative tumor front. Accumulating evidence suggests TB is an independent prognostic factor in oral squamous cell carcinoma (OSCC). However, its exact role is not yet elucidated, and a standardized scoring system is still necessary. The study aims to extensively review the literature data regarding the prognostic role of TB in OSCC. The results of TB are an independent prognostic factor of poor survival outcomes in OSCC. To date, the manual detection of hematoxylin and eosin-staining or pancytokeratin-immunostaining sections are the most commonly used methods. Between the several cut-offs, the two-tier system with five buds/field cut-offs provides better risk stratification. The prognostic role of the BD model in predicting survival outcomes was extensively validated; however, the inclusion of DOI, which is already a staging parameter, encouraged other authors to propose other models, integrating TB count with other adverse risk factors, such as the tumor–stroma ratio and tumor-infiltrated lymphocytes. The prognostic relevance of TB in OSCC highlights its evaluation in daily pathological practice. Therefore, the TB detection method and the TB scoring system should be validated based on tumor stage and site. [ABSTRACT FROM AUTHOR]

Western blot analysis and immunohistochemistry were carried out to evaluate PON2 expression levels in two different cohorts of matched cancer and normal tissue samples, obtained from patients affected from OSCC. Immuno-histochemistry was carried out to evaluate PON2 expression in tumor (C) and surrounding healthy margin (D) related with FFPE tissue samples obtained from 30 OSCC patients (200 × magnification). 1 PON2 protein level was evaluated in 11 paired tumor (T) and normal (N) tissue specimens collected from patients affected with OSCC. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

The aims of this study were to propose an automatic color-based segmentation method to separate mixed and unmixed colors of images that were derived from the application of the two-color chewing-gum mixing test and to determine the validity of this method in the assessment of masticatory performance (MP). Fifty young adults (mean age: 24.3 ± 2.7 years) were enrolled in the study. Each participant chewed a double-colored chewing gum for 5, 10, 20, 30, and 50 masticatory cycles. Boluses were collected and flattened. Both sides of each bolus were photographed, and images were processed using a novel k-means clustering method. The specimens corresponding to 20 masticatory cycles were re-analyzed by the same investigator in order to evaluate the intra-rater reliability and by a second investigator to assess the inter-rater reliability. To assess the test–retest reliability, 25% of the participants performed a second test with 20 chewing cycles. Each bolus was subjectively scored as either poorly, moderately, or highly mixed by an investigator to assess the construct validity. The percentage of mixed colors in the samples increased with an increase in the number of strokes. Significative differences were detected when varying from 5 to 10 strokes, from 10 to 20 strokes, and from 30 to 50 strokes (p < 0.05). The Pearson correlation coefficient explained these relations (r = 0.78, p < 0.05). The interclass correlation coefficient (ICC) showed a good correlation concerning both the intra- and inter-rater reliability (r = 0.85 and r = 0.77, respectively) and an excellent test–retest correlation (r = 0.93). The subjective assessment was coherent with the digital one. The proposed digital method was proved to be able to automatically quantify the percentage of the mixed color area by providing quantitative data with minimal human interaction. [ABSTRACT FROM AUTHOR]

Background: In patients with squamous cell carcinoma of the oral tongue (OTSCC), current tumor node metastasis staging system fails to identify at‐risk patients associated with early relapse and poor prognosis despite complete surgical resection. Given the importance of tumor‐infiltrating lymphocytes (TILs) in the development of cancers, here we investigated the prognostic significance of the immune phenotype in OTSCC. Methods: Hematoxylin‐eosin stained sections of OTSCCs from 211 patients were evaluated. Cancers were classified as (a) immune‐inflamed when TILs were found next to tumor cell nests; (b) immune‐excluded when TILs were found in the stroma, outside the tumor; and (c) immune‐desert for tumors lacking lymphocyte infiltrate. The prognostic significance of these immune phenotypes classes was investigated. Data were further validated on an independent cohort from The Cancer Genome Atlas database. Results: Immune‐desert phenotype was the least represented group of OTSCCs in our cohort (11.8%) and served as an independent prognostic factor. Patients with immune‐desert tumors exhibited worse disease‐specific survival (HR = 2.673; [CI: 95% 1.497‐4.773]; P =.001), overall survival (HR = 2.591; [CI: 95% 1.468‐4.572]; P =.001), and disease‐free survival (HR = 2.313; [CI: 95% 1.118‐4.786]; P =.024) at multivariate analysis. Conclusions: We identified a specific subgroup of OTSCCs with poor prognosis. Tumor‐infiltrating lymphocytes density and localization could serve as an integrative parameter to the current staging system and inform the selection of most appropriate treatments. In particular, the tumor immune phenotype could improve the stratification of patients with more aggressive disease. [ABSTRACT FROM AUTHOR]

Aims: One of the objectives of current research is to customise the treatment of cancer patients. The achievement of this objective requires stratification of patients based on the most significant prognostic factors. The aims of this study were to evaluate the prognostic value of the tumour–stroma ratio (TSR), defined as the proportion of tumour cells relative to surrounding stroma, in patients with oral tongue squamous cell carcinoma (OTSCC), and to develop a prognostic nomogram based on the most significant clinicopathological features. Methods and results: Clinicopathological data of 211 patients treated at 'Ospedali Riuniti' General Hospital (Ancona, Italy) for OTSCC were collected. One hundred and thirty‐nine patients were restaged according to the 8th edition American Joint Committee on Cancer (AJCC) staging system. Evaluation of the TSR was performed on haematoxylin and eosin‐stained slides, and correlation with survival outcomes was evaluated. In addition, with the aim of integrating the independent value of the TSR with the 8th edition AJCC staging system, a prognostic nomogram for OTSCC has been developed. OTSCC with a low TSR (i.e. a high proportion of stroma and a low proportion of tumour cells) was shown to have negative prognostic value in terms of disease‐specific survival, with a hazard ratio (HR) of 1.883 and a 95% confidence interval (CI) of 1.033–3.432 (P = 0.039), and overall survival (HR = 1.747, 95% CI 0.967–3.154; P = 0.044), independently of other histological and clinical parameters. For the cohort of 139 patients restaged according to the 8th edition AJCC staging system, variables correlating with a poor prognosis were: the TSR, perineural invasion, and sex. The nomogram built on these parameters showed good predictive capacity, outperforming the 8th edition AJCC staging system in stratifying disease‐specific survival in OTSCC patients. Conclusions: Including the TSR in the predictive model could improve risk stratification of OTSCC patients and aid in making treatment decisions. [ABSTRACT FROM AUTHOR]

Objectives: The frequency of oral squamous cell carcinoma in young adults has increased in the last decades, and there are conflicting results in literature about its prognosis in young subjects. The aim of this study was to analyse the clinical and pathological features of oral squamous cell carcinoma in a cohort of young adults in order to investigate the presence of new independent prognostic markers. Materials and Methods: Only HPV‐negative young patients (under 40‐year‐old) affected by oral squamous cell carcinoma were considered in this study. Clinical and pathological data were collected. Patients were re‐staged according to the 8th edition of AJCC. Results: Overall, 66 patients were considered in this study. Perineural invasion significant correlated with both 7th and 8th edition of AJCC, and lymphovascular invasion (p‐value <.05). The multivariate survival analysis showed that patients with perineural invasion had a significant worse prognosis (HR = 6.384 95% C.I. 1.304–31.252; p‐value =.022). Conclusions: Perineural invasion emerged as an independent prognostic factor for disease‐specific survival in young patients with oral squamous cell carcinoma. Furthermore, the evaluation of this parameter is simple, inexpensive and can be used to augment the risk stratification of oral cancer based on the 8th edition of AJCC. [ABSTRACT FROM AUTHOR]

Background: Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long‐term clinical and radiological follow‐up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N‐methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). Materials and methods: A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. Results: NNMT expression was significantly higher in recurrent than primary AMs (P =.0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P =.0470). NNMT expression was significantly lower in recurrent than primary OKC (P =.0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P =.0276). Conclusions: This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker. [ABSTRACT FROM AUTHOR]

Salivary glands (SG) arise from ectodermal tissue between 6 and 12th weeks of intrauterine life through finely regulated epithelial-mesenchymal interactions. For this reason, different types of structural congenital anomalies, ranging from asymptomatic anatomical variants to alterations associated with syndromic conditions, have been described. Notable glandular parenchyma anomalies are the SG aplasia and the ectopic SG tissue. Major SG aplasia is a developmental anomaly, leading to variable degrees of xerostomia, and oral dryness. Ectopic SG tissue can occur as accessory gland tissue, salivary tissue associated with branchial cleft anomalies, or true heterotopic SG tissue. Among salivary ducts anomalies, congenital atresia is a rare developmental anomaly due to duct canalization failure in oral cavity, lead to salivary retention posterior to the imperforate orifice. Accessory ducts originate from the invagination of the developing duct in two places or from the premature ventral branching of the main duct. Heterotopic ducts may arise from glandular bud positioned in an anomalous site lateral to the stomodeum or from the failure of the intraoral groove development, hindering their proximal canalization. These anomalies require multidisciplinary approach to diagnosis and treatment. While ectopic or accessory SG tissue/ducts often do not require any treatment, patients with SG aplasia could benefit from strategies for restoring SG function. This article attempts to review the literature on SG parenchyma and ducts anomalies in head and neck region providing clinicians with a comprehensive range of clinical phenotypes and possible future applications of bioengineered therapies for next-generation of regenerative medicine. [ABSTRACT FROM AUTHOR]

An altered oral microbiota has been linked with the development of several oral diseases, such as dental caries, periodontal disease, and oral stomatitis. Moreover, poor oral health has been linked to head and neck cancer, particularly oral cancer. In recent years a growing number of studies indicate that oral microbiota could be involved in the development of primary tumours outside of head and neck region. The aim of this article is to review the recent studies based on high-throughput technology to present evidences of a relationship between oral microbiota and "non-head and neck tumours." Oral dysbiosis seem to be more pronounced in patients with tumours of gastrointestinal tract, in particular oesophageal, gastric, pancreatic, and colorectal cancers, paving the way for developing specific oral microbiota test to allow early cancer detection. Regarding other tumour types, the results are promising but highly preliminary and still debated. Currently, there are several factors that limit the generalization of the results, such as the small sample size, the lack of adequate clinical information about patients, the different sequencing techniques used, and biological sample heterogeneity. Although only at the beginning, the analysis of oral microbiota could be the next step in the evolution of cancer therapy and will help clinicians to develop individualised approaches to cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Objective: In this study, we evaluated the 8th edition of American Joint Committee on Cancer (AJCC) staging criteria and lymph node ratio (LNR) to identify patients affected by squamous cell carcinoma of the tongue (SCCT) with a poor prognosis.Study Design: Seventy-three cases of SCCT were analyzed retrospectively. Tumor staging was revised according to the 7th and 8th editions of the AJCC criteria. Depth of invasion (DOI), extranodal extension (ENE), and LNR were evaluated.Results: Twenty-five cases were reclassified: 17 patients received an upstage in the staging score, and in 8 cases in the same stage group, pT or pN was changed. In the pT-upstaged group, 7 patients experienced recurrence, and 8 died. In the pN-upstaged group, 9 patients developed recurrence, and 10 died. The number of disease recurrence or death was higher in the groups of patients who received an upstage in pN and in the staging score (P < .05). The pN-upstaged group showed worse disease-free survival (DFS) and overall survival (OS) (P < .05). LNR was higher in patients with recurrence, and among these, LNR was lower in patients with ENE (P <.05).Conclusions: The 8th edition of the AJCC criteria allows for better stratification of patients with SCCT. The implementation of ENE and LNR to pN classification seems to identify patients with worse DFS and OS. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, and despite advances in cancer therapies, the overall 5-year survival rate has remained below 50% over the past decades. OSCC is typically preceded by potentially malignant disorders (PMD), but distinguishing high-risk from low-risk PMD is challenging. In the last years, several diagnostic methods as light-based detection systems (LBDS) have been proposed to facilitate the detection of OSCC and PMD. Furthermore, the recent evolution of nanotechnology may provide new opportunities to detect PMD and OSCC at an early stage. Indeed, several preclinical studies showed the potential of nanotechnology to enhance diagnostic accuracy. For these reasons, it is fundamental to conduct studies to evaluate the efficacy of nanotechnology implementation in LBDS. The aim of this article is to review the current literature on LBDS and to provide a summary of the sensitivity and specificity of each technique, and possible future applications of nanotechnologies. The LBDS showed great potential for screening and monitoring oral lesions, but there are several factors that hinder an extensive use of these devices. These devices seem to be useful in assessing lesion margins that must be biopsied. However, to date, conventional oral examination, and tissue biopsy remain the gold standard for OSCC diagnosis. The use of nanotechnologies could be the next step in the evolution of LBDS, thus providing devices that can help clinicians to detect and better monitor oral lesions. [ABSTRACT FROM AUTHOR]

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) are multipotent cells able to differentiate into specialized cells developing from mesoderm and to regenerate different tissues [[1]]. Lorenzo Lo Muzio Marco Mascitti Marcella La Noce Francesca Posa Yasusei Kudo Nicola Cirillo REFERENCES 1 Dimarino A. M., Caplan A. I., Bonfield T. L. Mesenchymal stem cells in tissue repair. Interestingly, L. Li et al. have demonstrated the ability of the microporous composites, developed combining OPF/BP with SDF-1 I i , in promoting migration and osteogenic differentiation of rat bone marrow MSCs (BMSCs), which makes it a good material useful to increase bone regeneration. [Extracted from the article]

Odontogenic tumors are a group of lesions arising from the odontogenic apparatus. Although the mechanism of oncogenesis and tumor progression in these lesions remains unknown, certain proteins, such as those involved in apoptosis, seem to be involved in the differentiation and proliferation of odontogenic epithelial cells. The aim of this study was to analyze the expression of p73 and TNF-related apoptosis-inducing ligand (TRAIL) in odontogenic tumors and cysts, and to clarify changes in the expression of these proteins. Immunohistochemical analysis was performed on 21 ameloblastomas, 15 keratocystic odontogenic tumors and 15 dentigerous cysts. We carried out quantitative assessment of p73 and TRAIL expression by determining the percentages of positive cells on a continuous scale. Five cases of orthokeratinized odontogenic cyst were also examined. The percentages of cells immunohistochemically positive for p73 were 52.6 ± 25.4% in ameloblastomas, 76.0 ± 13.1% in keratocystic odontogenic tumors, and 26.7 ± 30.7% in odontogenic cysts, whereas the corresponding figures for TRAIL were 57.6 ± 16.1%, 8.9 ± 10.0%, and 1.5 ± 0.5%, respectively. Imbalance of the apoptosis pathway, with dysregulation of p73 and TRAIL, seems to play a role in the oncogenesis of odontogenic tumors.(J Oral Sci 58, 459-464, 2016). [ABSTRACT FROM AUTHOR]

The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT. [ABSTRACT FROM AUTHOR]

Oral cancer is the most common tumor of the head and neck region. Its management is based on surgical and systemic therapies. Taste disorders represent the most common side effect of these treatments; indeed, dysgeusia is noted by 70% of oral cancer patients. Despite survival remaining the primary endpoint of cancer patients, taste impairments can cause psychological distress. This comprehensive review describes the last decade's knowledge from the literature regarding taste alterations in patients with oral and oropharyngeal squamous cell carcinoma. A total of 26 articles in English, including prospective, cross-sectional, and case–control studies, and clinical trials were evaluated. Literature analysis shows that anti-cancer treatments can destroy taste cells, decrease and alter their receptors, and interrupt nerve transmission. Furthermore, the tumour itself can destroy the oral mucosal lining, which encloses the taste buds. Dysgeusia typically occurs in 3–4 weeks of treatments, and usually taste sensation is recovered within 3–12 months. However, some patients exhibit incomplete or no recovery, even several years later. Thus, dysgeusia can become a chronic issue and negatively influence patients' quality of life, worsening their dysphagia and their nutritional status. Physicians should be focused on preventing oncological treatment-related symptoms, offering the most suitable personalized support during therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer (HNC) is a complex and extremely heterogeneous disease that includes a wide variety of cancer subtypes. Despite notable advances in understanding the molecular mechanisms involved in the disease, which allowed the increase of the therapeutic armamentarium, HNC treatment remains very challenging. In fact, to date the average 5-year survival rate for this disease is around 65%; hence, HNC continues to be one of the most aggressive solid tumors. Surgical removal is the first treatment of choice for HCN; however, in addition to this treatment modality, a broad spectrum of new therapies has been developed so far, ranging from multimodal chemotherapy to targeted and immune-therapy, mainly through the use of antibodies. In this work, we systematically reviewed the progress obtained in antibody-drug conjugate (ADC) development for the treatment of HNC. Background: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC. Methods: This review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database. Results: In total, 19 studies were included. Due to the significant heterogeneity of the outcome measures, meta-analysis was not performed, and data were summarized in tables. HNC results are poorly represented in the cohorts of completed clinical trials; published data are mostly focused on safety evaluation rather than efficacy of ADCs. Conclusions: Although several novel agents against a wide range of different antigens were investigated, showing promising results at a preclinical level, most of the targets reported in this review are not specific for HNC; hence, the development of ADCs tailored for the HNC phenotype could open up new therapeutic perspectives. Moreover, the results from the present systematic review call attention to how limited is the application of current clinical trials in HNC. [ABSTRACT FROM AUTHOR]