BCAT1 promotes cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway in oral squamous cell carcinoma.

OBJECTIVES: To analyze the expression, biological function of branched chain amino-acid transaminase 1 (BCAT1) in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Real-time PCR and immunohistochemistry were used to analyze the expression of BCAT1 protein in OSCC and normal oral tissues. Based on the clinicopathological information of patients, the relationship between the expression of BCAT1 protein and other clinicopathological factors was analyzed. Real-time PCR and western blot assays were used to analyze the expression of BCAT1 gene and protein in normal human oral keratinocytes (HOK) and human OSCC cells, respectively. After BCAT1 overexpression or knockdown, the proliferation, cell cycle, migration, and invasion of human OSCC cells were analyzed by CCK8, flow cytometry, wound healing, and transwell invasion assays, respectively. After adding the BCAT1 inhibitor EGR240 to OSCC cells, the changes in cell proliferation, migration, and invasion ability in OSCC cells were analyzed. Based on the TCGA database, the involved signal pathway in BCAT1-related and BCAT1-binding genes was obtained for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, verified by western blot assays. After inhibiting PI3K, the effect of BCAT1 on the expression of the downstream phosphorylated protein of the PI3K-Akt signaling pathway was analyzed by western blot assays. The relationship between the expression of BCAT1 and EMT-related protein of OSCC cells was also analyzed. RESULTS: The expression of BCAT1 gene and protein were upregulated in OSCC tissue, which positively correlated with the pathological grade of patients with OSCC. Compared with normal oral keratinocytes, BCAT1 gene and protein were upregulated in OSCC cells. BCAT1 overexpression promoted the proliferation, migration, and invasion of OSCC cells. BCAT1 knockdown or inhibition could reduce the proliferation, migration, and invasion abilities of OSCC cells. The results of bioinformatics analysis and Western bolt showed that BCAT1 could regulate the activation of PI3K-Akt signaling pathway, and promote epithelial-mesenchymal transition (EMT) of OSCC cells. CONCLUSIONS: BCAT1 could promote the proliferation, migration, and invasion of OSCC cells via PI3K-Akt signaling pathway, which is a potential therapeutic target for OSCC.

Soluble CD44 in oral rinses for the early detection of cancer: a prospective cohort study in high-risk individuals.

BACKGROUND: There are 54,000 new cases of oral cavity and oropharyngeal cancer in the United States and more than 476,000 worldwide each year. Oral cavity and oropharyngeal squamous cell carcinoma make up most tumors with five-year survival rates of 50% due to prevalence of late-stage diagnoses. Improved methods of early detection in high-risk individuals are urgently needed. We aimed to assess the tumorigenic biomarkers soluble CD44 (solCD44) and total protein (TP) measured using oral rinses as affordable convenient screening tools for cancer detection. METHODS: In this prospective cohort study, we recruited 150 healthy current or former smokers through a community screening program. Baseline and four annual visits were conducted from March 2011-January 2016 with records followed until August 2020. Participants provided oral rinses, received head and neck exams, and completed questionnaires. SolCD44 and TP levels were measured and compared across groups and time. Participants were placed in the cancer group if malignancy developed in the study period, the suspicious group if physical exams were concerning for premalignant disease or cancer in the head and neck, and the healthy group if there were no suspicious findings. This analysis used two-sample t-test for comparison of means and two-sample Wilcoxon Test for comparison of medians. For subjects with follow-ups, estimated means of biomarkers were obtained from a fitted Repeated Measures Analysis of Variance (RANOVA) model including group, visit, and their interaction. Pairwise comparisons of mean solCD44 were made, including intergroup and intragroup comparison of values at different years. RESULTS: Most participants were males (58.7%), < 60 years of age. (90.7%), and Black (100%). Baseline mean solCD44 was elevated (2.781 ng/ml) in the cancer group compared to the suspicious group (1.849 ng/ml) and healthy group (1.779 ng/ml). CONCLUSION: This study supports the feasibility of a CD44-based oral rinse test as an affordable and convenient adjunctive tool for early detection of aerodigestive tract and other cancers in high-risk populations.

Reconstruction of Defects After Oral Cancer Surgery With the Superior Thyroid Artery Perforator Flap.

OBJECTIVE: The superior thyroid artery perforator flap (STAPF) was previously presented as a type of locoregional pedicled flap for lateral facial and temple defects. In this study, we aimed to present our clinical experience with this flap for the reconstruction of soft tissue defects after oral cancer surgery. METHODS: From February 2019 to December 2022, 24 patients with oral cancers at the School and Hospital of Stomatology, Peking University were included. Among these patients, 10 had cancers located in the tongue, five in the cheek inside the oral cavity, three in the lower gingiva, two in the upper gingiva, two in the floor of the mouth, and two in the palate. All patients were treated with extended tumor resection, neck dissection, and STAPFs to reconstruct the soft tissue defects. The details of the flap, including the flap size, venous flow, vascular pedicle length, the attatched muscle, and operation time were evaluated. RESULTS: The dimensions of the flap skin paddle ranged from 3 cm × 5 cm to 6 × 14 cm. Fourteen patients had a closely concomitant superior thyroid vein perforator. Ten patients had non-closely concomitant superior thyroid veins perforators which retrograde external jugular vein. The vascular pedicle length ranged from 5 to 9 cm. The infrahyoid muscle group or sternocleidomastoid muscle was included in the flaps in three patients. A total of 23/24 flaps were successful. CONCLUSIONS: The STAPF is a viable reconstructive option for patients with oral cancers. It has the advantages of being robust, being thin, short operation time, and minor donor site complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Efficacy of tracheostomy for respiratory management in patients with advanced oral cancer.

BACKGROUND: Many studies have been reported on tracheostomy to prevent upper airway obstruction after surgery. Among these, the scoring system proposed by Cameron et al. quantifies various factors that influence postoperative respiratory failure. This system provides a basis for surgeons to decide whether to perform an elective tracheostomy. In this study, the authors applied the Cameron scoring system retrospectively to patients undergoing severe oral cancer surgery to reevaluate the indications for elective tracheostomy and to investigate its clinical efficacy in airway management. In this study, a sample of 20 patients who underwent oral cancer surgery was selected and divided into two groups: 10 underwent tracheostomy and 10 did not. The Cameron scoring scores for each patient were extracted, to verify whether elective tracheostomy was performed in accordance with the threshold scores. Differences in scores and significant clinical impact factors between the two groups were analyzed and compared. RESULT: The 10 patients who underwent tracheostomy had an average Cameron score of 6.4, all scoring above the recommended threshold of 5 for tracheostomy. For the 10 patients who did not undergo tracheostomy, the average score was 2.5, with 8 out of these 10 patients scoring below 5. Significant clinical impact factors observed included the location and size of the tumor, the performance of mandibulectomy and neck dissection, and the type of reconstruction surgery. CONCLUSION: In planning surgery for oral cancer patients, it is essential to consider the use of elective tracheostomy based on preoperative assessment of the risk of postoperative airway obstruction using tools like the Cameron scoring system, and patients' condition. Research confirms that elective tracheostomy effectively enhances airway management in patients with severe oral cancer.

A deep learning approach to detection of oral cancer lesions from intra oral patient images: A preliminary retrospective study.

INTRODUCTION: Oral squamous cell carcinomas (OSCC) seen in the oral cavity are a category of diseases for which dentists may diagnose and even cure. This study evaluated the performance of diagnostic computer software developed to detect oral cancer lesions in intra-oral retrospective patient images. MATERIALS AND METHODS: Oral cancer lesions were labeled with CranioCatch labeling program (CranioCatch, Eskisehir, Turkey) and polygonal type labeling method on a total of 65 anonymous retrospective intraoral patient images of oral mucosa that were diagnosed with oral cancer histopathologically by incisional biopsy from individuals in our clinic. All images have been rechecked and verified by experienced experts. This data set was divided into training (n = 53), validation (n = 6) and test (n = 6) sets. Artificial intelligence model was developed using YOLOv5 architecture, which is a deep learning approach. Model success was evaluated with confusion matrix. RESULTS: When the success rate in estimating the images reserved for the test not used in education was evaluated, the F1, sensitivity and precision results of the artificial intelligence model obtained using the YOLOv5 architecture were found to be 0.667, 0.667 and 0.667, respectively. CONCLUSIONS: Our study reveals that OCSCC lesions carry discriminative visual appearances, which can be identified by deep learning algorithm. Artificial intelligence shows promise in the prediagnosis of oral cancer lesions. The success rates will increase in the training models of the data set that will be formed with more images.

Perimarginal quadrangle dissection: Pushing the boundaries of neck dissection in gingivo-buccal complex cancer.

OBJECTIVES: Perimarginal nodes (PMN) lie in close relationship with marginal mandibular nerve (MMN), in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible and remain unaddressed in conventional neck dissection. We have aimed to define the boundaries of perimarginal node dissection, explore incidence of PMN metastasis and its correlation with histopathological characteristics. MATERIALS AND METHODS: A prospective study was conducted on 112 consecutive patients of GB carcinoma. PMN dissection was performed in an anatomically defined quadrangle. Prospective clinical characteristics included subsite, tumor and nodal stage, location of primary and clinical skin involvement. Histopathological characteristics analyzed included grade, size, pathological tumor, nodal stage, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN function was graded at 3 and 6 months post-operatively. RESULTS: The PMN were identified histologically in 75.89 % patients. 15.2 % patients harboured metastasis in PMN. 16.7 % patients had clinically occult metastasis with 11.7 % having isolated PMN metastasis. None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p = 0.01) and pathological skin involvement (p = 0.03) were found statistically significant on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. CONCLUSION: There is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent predictors for PMN metastasis. PMN dissection must be performed in all cases of GB cancer.

Formulation of 1% α-mangostin in orabase gel induces apoptosis in oral squamous cell carcinoma.

BACKGROUND: Plant-derived compounds have chemopreventive properties to be used as alternative medicine. Pericarp of Mangosteen (Garcinia mangostana Linn.), a tropical fruit in Southeast Asia contains a phytochemical α-mangostin (α-MG) that demonstrates potent anticancer effects against various types of cancer. α-MG has been reported to be the most effective agent in human cancer cell lines. The objectives of this study were to develop oral gel formulations containing α-MG and determine their (1) anticancer activity, (2) anti-HPV-16 and antimicrobial activities, (3) nitric oxide (NO) inhibitory activity, and (4) wound healing effect. METHODS: Formulations of oral gel containing α-MG were developed. Anticancer activity on SCC-25 was assessed. Apoptotic induction was determined using flow cytometry technique. Antiviral activity against HPV-16 pseudovirus and antimicrobial activity against S. mutans, P. gingivalis and C. albicans were investigated. NO inhibition was carried out. Fibroblast cell migration was determined by in vitro scratch assay. RESULTS: The formulation of 1% α-MG in orabase gel demonstrated anticancer activity by promoting apoptosis in SCC-25. The induction of apoptotic activity was dose dependent with pronounced effect in late apoptosis. The formulation appeared to reduce cell viability of oral keratinocytes (OKC). At CC50 it showed an inhibition against HPV-16 pseudovirus infection. The formulation had no antimicrobial activity against S. mutans, P. gingivalis and C. albicans. No significant NO inhibitory activity and wound healing effects were found. CONCLUSIONS: 1% α-MG in orabase gel exhibited anticancer activity by inducing apoptosis although low level of cytotoxicity observed in OKC was present. The appropriate carrier for novel nano-particles targeting cancer cells should be further investigated.

Stimuli-Responsive Nanocomposite Hydrogels for Oral Diseases.

Oral diseases encompassing conditions such as oral cancer, periodontitis, and endodontic infections pose significant challenges due to the oral cavity's susceptibility to pathogenic bacteria and infectious agents. Saliva, a key component of the oral environment, can compromise drug efficacy during oral disease treatment by diluting drug formulations and reducing drug-site interactions. Thus, it is imperative to develop effective drug delivery methods. Stimuli-responsive nanocomposite hydrogels offer a promising solution by adapting to changes in environmental conditions during disease states, thereby enabling targeted drug delivery. These smart drug delivery systems have the potential to enhance drug efficacy, minimize adverse reactions, reduce administration frequency, and improve patient compliance, thus facilitating a faster recovery. This review explores various types of stimuli-responsive nanocomposite hydrogels tailored for smart drug delivery, with a specific focus on their applications in managing oral diseases.

Anti-Cancer Activities of Nano Amorphous Calcium Phosphates toward Premalignant and Oral Cancer Cells.

Despite advancements in treatment, the squamous cell carcinoma (OSCC) patient survival rate remains stagnant. Conventional therapies have limited effectiveness, necessitating novel agents. Our study aims to synthesize and characterize amorphous calcium phosphate nanoparticles (nACPs), assess their potential cytotoxic effects on premalignant and malignant OSCC cells, and investigate possible mechanisms of action. The morphological features of nACP were investigated by field emission scanning coupled with energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and particle size distribution (PSD). Then, we examined the effect of nACPs on nanoparticle uptake, cell adhesion, viability, invasion ability, cell cycle, and gene expression. nACP uptake was dose-dependent, induced limited selectivity in cytotoxicity between healthy and malignant cells, and affected cellular adhesion and invasion. Early apoptosis was the predominant type of cell death. The nACP effect on viability was verified by alterations in the genes associated with apoptosis and proliferation. A high concentration of nACP was shown to arrest the cell cycle progression in the G0/G1 phase of both malignant and premalignant cells. This type of nACP justifies the development of a strategy for its potential use as an anti-cancer agent and/or anti-cancer active carrier for various drugs in oral cancer treatments.

A Roadmap for the Rational Use of Biomarkers in Oral Disease Screening.

Oral health has witnessed a significant transformation with the integration of biomarkers in early-diagnostic processes. This article briefly reviews the types of biomarkers used in the screening and early detection of oral diseases, particularly oral cancer, periodontal diseases, and dental caries, with an emphasis on molecular biomarkers. While the advent of these biomarkers may represent a leap forward in oral healthcare, it also opens the door to potential overtesting, overdiagnosis, and overtreatment. To inform the selection of novel biomarkers and ensure their rational use in screening tests, it is imperative to consider some key characteristics, which are specific to the biomarker (e.g., surrogate biomarkers should reliably reflect the primary health outcome), to the test (e.g., sensitivity and specificity must be balanced based on the disease of interest), and to the disease (e.g., the efficacy of treatment should improve when the condition is diagnosed earlier). For systemic conditions associated with oral diseases, researchers should be extremely cautious when determining who is "at risk", particularly when such risk is small, non-existent, or inconsequent. This framework aims to ensure that advancements in oral health diagnostics translate into genuine improvements in patient care and well-being.

A comprehensive dataset of annotated oral cavity images for diagnosis of oral cancer and oral potentially malignant disorders.

OBJECTIVES: This study aims to address the critical gap of unavailability of publicly accessible oral cavity image datasets for developing machine learning (ML) and artificial intelligence (AI) technologies for the diagnosis and prognosis of oral cancer (OCA) and oral potentially malignant disorders (OPMD), with a particular focus on the high prevalence and delayed diagnosis in Asia. MATERIALS AND METHODS: Following ethical approval and informed written consent, images of the oral cavity were obtained from mobile phone cameras and clinical data was extracted from hospital records from patients attending to the Dental Teaching Hospital, Peradeniya, Sri Lanka. After data management and hosting, image categorization and annotations were done by clinicians using a custom-made software tool developed by the research team. RESULTS: A dataset comprising 3000 high-quality, anonymized images obtained from 714 patients were classified into four distinct categories: healthy, benign, OPMD, and OCA. Images were annotated with polygonal shaped oral cavity and lesion boundaries. Each image is accompanied by patient metadata, including age, sex, diagnosis, and risk factor profiles such as smoking, alcohol, and betel chewing habits. CONCLUSION: Researchers can utilize the annotated images in the COCO format, along with the patients' metadata, to enhance ML and AI algorithm development.

Is immediate dental implant in fibula free flap beneficial for implant survival and osteoradionecrosis in jaw reconstruction?

OBJECTIVES: This study aimed to compare the risk of osteoradionecrosis and implant survival in oral cancer patients undergoing immediate dental implants during jaw reconstruction, termed "Jaw in a Day" (JIAD), with those receiving no implants or delayed implants (non-JIAD). PATIENTS & METHODS: Clinicopathologic data were collected from prospectively enrolled JIAD patients (n = 10, 29 implants) and retrospectively from non-JIAD patients (n = 117, 86 implants). Survival analyses were performed to assess implant survival and osteoradionecrosis-free survival. RESULTS: Osteoradionecrosis occurred in 0 % of JIAD cases compared to 19.3 % in non-JIAD cases without implants and 71.4 % in non-JIAD cases with delayed implants (p = 0.008). Osteoradionecrosis-free survival was significantly better in the JIAD group than the non-JIAD group (p = 0.0059). Implants in the JIAD group all survived regardless of radiation therapy (29/29, 100 %) and 95.1 % (58/61) of implants survived in delayed implants in non-irradiated fibula without radiotherapy. Meanwhile, only 11 of 25 implants placed in irradiated fibula flaps survived, even when the implants were placed after a median time interval of 624 days after radiotherapy, and none of them were earlier than 360 days. The survival analysis revealed a significant difference (p < 0.0001). CONCLUSION: JIAD appears to offer superior outcomes in terms of implant survival and osteoradionecrosis prevention compared to delayed implant placement. Placing implants in irradiated fibula, even after years, significantly poses high risk of implant failure and osteoradionecrosis. JIAD represents a promising approach for optimal rehabilitation, particularly in oral cancer patients requiring postoperative radiotherapy. Proper positioning and orientation of implants and flaps are crucial for implant survival.

Comment on, "Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date".

This study by Shridhar et al. 2016 reviews the genetic susceptibility to oral potentially malignant disorders (OPMD) through the analysis of single nucleotide polymorphisms (SNPs). By examining data from 47 studies conducted between 2000 and 2016, the research highlights genetic markers involved in carcinogen metabolism, DNA repair, cell cycle control, and immune-inflammatory responses. Despite the insights provided, the over-reliance on small sample sizes limits the statistical power and generalizability of the findings. Future research should focus on larger, more diverse populations and advanced genotyping technologies to enhance detection of significant genetic variants. Integrating multi-omics data and conducting longitudinal studies will further elucidate the molecular mechanisms underlying OPMD and its progression to oral cancer. Collaborative efforts are essential to validate these findings and develop biomarkers for early detection and prevention.

Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer.

BACKGROUND AND AIMS: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.

What prognostic factors have impacted the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic oral cancer?

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely adapted for recurrent or metastatic head and neck cancer (RM-HNC), and various studies on its prognostic factors have been reported. We aimed to elucidate the prognostic factors of ICI treatment for RM oral cancer (RM-OC) in a retrospective study. METHODS: We retrospectively reviewed patients with RM-OC treated with ICIs (nivolumab and pembrolizumab) at our department from May 2017 to February 2023. The objective response rate (ORR) for ICI treatment and the relationship between several potential prognostic factors, progression-free survival (PFS), and overall survival (OS) were analyzed statistically. RESULTS: The investigation enrolled 31 patients, 16 with nivolumab and 15 with pembrolizumab. There were no significant differences in the ORR or disease control rate between the nivolumab and pembrolizumab groups (p = 0.4578 and 0.2524). In multivariate analysis, the prognostic nutritional index (PNI) and C-reactive protein to albumin ratio (CAR) exhibited statistical correlations with PFS, whereas the use of antibiotics and proton pump inhibitors (PPIs), neutrophil to lymphocyte ratio (NLR), and PNI demonstrated statistical associations with OS. CONCLUSION: Our findings imply that the use of antibiotics and PPIs, which can modify the gut microbiota, may also serve as a prognostic determinant for ICI treatment in RM-OC, consistent with previous studies. Additionally, PNI may be essential in affecting the survival rates of both PFS and OS and could be an exceedingly valuable inflammatory biomarker for RM-OC.

A Concordance Between Clinical and Pathological Tumor Staging of Oral Squamous Cell Carcinoma: An Institutional Study.

BACKGROUND: Among oral diseases, oral cancer is the primary cause of death and poses a serious health risk. Primary tumor (T) - regional lymph node (N) - distant metastasis (M) comprising (TNM) staging is crucial for planning treatment strategies for patients with oral squamous cell carcinoma (OSCC). AIM: This study evaluated the predictive accuracy of clinical TNM staging of OSCC to histopathological staging (pTNM) in an institutional setting. MATERIALS AND METHODS: Fifty-four consecutive histologically confirmed, surgically treated OSCC cases were evaluated for TNM staging. The study compared the clinical staging at the time of surgery with the pathological staging obtained from excisional biopsy reports. Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) was used for the data compilation and descriptive analysis. The chi-square test, analysis of variance (ANOVA), and Tukey's Honest Significant Difference (HSD) posthoc test were used to compare the data for statistical significance with p value <0.05 using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 23.0, Armonk, NY). RESULTS: The alveolar mucosa (n=22, 40.74%) was the most frequently occurring site, followed by the tongue (n=17, 31.48%). Out of the 54 included cases, based on clinical tumor size, there were T1 (n=6), T2 (n=13), T3 (n=13), T4a (n=16) and T4b (n=6). T2 tumors were usually upstaged (n=7) while T4a (n=8) tumors were most often downstaged. T4a (n=8) had the best concordance between clinical and histopathological staging, followed by T2, T3, and T1. In nodal status, N1 showed the most variation. The chi-squared test showed statistical significance for tumor size comparison (p <0.001) and nodal status comparison (p=0.002). ANOVA test did not show any statistical significance. Tukey's HSD posthoc test showed statistical significance (p=0.034) for N0 and N1 status. The highest concordance was shown by N0 and N1 followed by N2b. CONCLUSION: Preoperative radiological and clinical assessments are essential for deciding on a patient's course of treatment. However, not all patients may require radiographs to determine tumor size or nodal status assessment. Accurate diagnosis is vital for the treatment planning of OSCC.

"Abraxane-Like" Radiosensitizer for In Situ Oral Cancer Therapy.

Radiotherapy plays a vital role in cancer therapy. However, the hypoxic microenvironment of tumors greatly limits the effectiveness, thus it is crucial to develop a simple, efficient, and safe radiosensitizer to reverse hypoxia and ameliorate the efficacy of radiotherapy. Inspired by the structure of canonical nanodrug Abraxane, herein, a native HSA-modified CaO2 nanoparticle system (CaO2-HSA) prepared by biomineralization-induced self-assembly is developed. CaO2-HSA will accumulate in tumor tissue and decompose to produce oxygen, altering the hypoxic condition inside the tumor. Simultaneously, ROS and calcium ions will lead to calcium overload and further trigger immunogenic cell death. Notably, its sensitizing enhancement ratio (SER = 3.47) is much higher than that of sodium glycididazole used in the clinic. Furthermore, in animal models of in situ oral cancer, CaO2-HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy-metal free biosafety, the CaO2-HSA-based radiosensitizer holds enormous potential for oral cancer therapy.

Concentration of High-Cost Head and Neck Cancer Surgical Patients.

OBJECTIVE: Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery. STUDY DESIGN: The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile. METHODS: Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality. RESULTS: Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44]). CONCLUSIONS: High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Dietary patterns suggest that dark chocolate intake may have an inhibitory effect on oral cancer: a Mendelian randomization study.

Background: Previous studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC). Materials and methods: We developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization. Results: Of the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622-0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574-0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect. Conclusion: This study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.

Prognostic triad: a novel method for decision-making for adjuvant treatment in stage I-II oral squamous cell carcinoma.

This study proposes a scoring system for adjuvant irradiation for stage I/II oral squamous cell carcinoma (OSCC). Derivation cohort (119 patients, operated between 2011 and 2014) and a validation cohort (204 patients, operated between 2016 and 2019) were included. In derivation cohort, on univariate analysis, tumor size >2 cm [3-year Disease Free Survival (DFS) 72.5% vs 95.6%, P = 0.039], lymphovascular invasion (58.3% vs 83.6%, P = 0.024), perineural invasion (75% vs 85.6%, P = 0.013), and depth of invasion ≥0.5 cm (73.8% vs 97.5%, P = 0.017) predicted 3-year DFS. Tongue lesions and poor differentiation were added as poor prognosticators based on previously published reports. Patients were grouped as low risk (<3 risk factors) and high risk (≥3 risk factors), with only high-risk group receiving adjuvant irradiation in validation cohort. Overall, 47/119 (39.5%) patients in the derivation cohort and 50/204 (24.5%) patients in validation cohort received adjuvant irradiation. In derivation cohort, 3-year DFS was 93% and 72.5% in the low and high-risk group, respectively. 3-year DFS was 90.7% and 85.8% in the low and high-risk group, respectively for validation cohort. The proposed scoring system reduced the use of adjuvant irradiation by 38%, with similar DFS.