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Oral cavity cancer exhibits high morbidity and mortality rates. Therefore, it is essential to diagnose the disease at an early stage. Machine learning and convolution neural networks (CNN) are powerful tools for diagnosing mouth and oral cancer. In this study, we design a lightweight explainable network (LWENet) with label-guided attention (LGA) to provide a second opinion to the expert. The LWENet contains depth-wise separable convolution layers to reduce the computation costs. Moreover, the LGA module provides label consistency to the neighbor pixel and improves the spatial features. Furthermore, AMSA (axial multi-head self-attention) based ViT encoder incorporated in the model to provide global attention. Our ViT (vision transformer) encoder is computationally efficient compared to the classical ViT encoder. We tested LWRNet performance on the MOD (mouth and oral disease) and OCI (oral cancer image) datasets, and results are compared with the other CNN and ViT (vision transformer) based methods. The LWENet achieved a precision and F1-scores of 96.97% and 98.90% on the MOD dataset, and 99.48% and 98.23% on the OCI dataset, respectively. By incorporating Grad-CAM, we visualize the decision-making process, enhancing model interpretability. This work demonstrates the potential of LWENet with LGA in facilitating early oral cancer detection. [ABSTRACT FROM AUTHOR]

The oral cancer treatment of choice is surgical excision with an organ preservation, if it is possible. Radiation therapy is commonly used as a postoperative treatment. Delivering radiation dose during surgery, defined as intraoperative radiotherapy (IORT), can be very useful especially in case of high risk of recurrence or where gross or macroscopic residual disease are present. The aim of this retrospective study is to evaluate the effectiveness of IORT combined with postoperative fractionated irradiation (EBRT) of patients with squamous cell carcinoma of the oral cavity. The study included 23 patients: IORT dose of 5–7.5 Gy was delivered using 50 kV X-rays generated by INTRABEAM™, combined with EBRT of 50–60 Gy in 25–30 fractions depending on presence of extracapsular invasion and narrow or positive surgical margins. Standard statistical tests were used. Median follow up was 64 months (range 8–222 months). The 5-year local tumour control was 92% and 82.5% in the 10-year follow-up. The 5-year overall survival (OS) was 56% and decreased to 45% during the next 5 years. There were no differences in the LTC, DFS and OS regarding sex, T-stage, grade and tumour localization, although a small group of analysed cases may raise some uncertainties. Acute side effects of combined IORT and EBRT were mild and no late complications occurred. The present study indicated that low-energy X-rays IORT combined with postoperative EBRT is a feasible and safe therapeutic modality which likely reduces a risk of locoregional recurrences. [ABSTRACT FROM AUTHOR]

Abstract Background Oral cavity cancer (OCC) represents a significant public health burden in South Asia, ranking as the most prevalent cancer affecting males in Pakistan and contributing considerably to morbidity and mortality. The objective of this study was to evaluate the survival rates in patients diagnosed with OCC in the Pakistani population and identify the factors influencing survival. Methods This was a retrospective cohort study conducted at the Aga Khan University Hospital Karachi, Pakistan. A total of 2238 cases diagnosed with OCC from May 2011 through December 2020, who met the inclusion criteria, were included. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Adjusted hazard ratios (HR) and their 95% confidence intervals (CIs) were estimated using a Cox regression model to identify the factors significantly influencing survival. Results Among all cases, 54.0% were diagnosed in individuals 50 years of age and below and 73.0% were tobacco users. Overall survival, 1-year, 3-year, and 5-year survival rates were 54.9%, 88.9%, 81.6%, and 75.9% respectively. After adjustment for all the significant confounding and prognostic factors, age was an important factor showing that adults > 50 years had poorer survival compared to ≤ 50 years (HR = 1.43, 95% CI = 1.11–1.83). Poorly differentiated grade of OCC compared to well-differentiated grade (HR = 2.49, 95% CI = 1.61–3.84) and stage IV compared to earlier stages (HR = 3.56, 95% CI = 2.13–5.94) were also associated with poor survival. Conclusion Notably, there was a high occurrence of late stage (III and IV) OCC in individuals aged ≤ 50 years, with the buccal mucosa being the most common site involved. Moreover, a large proportion of our patients had a history of tobacco use. Patients with advanced-stage disease and poorly differentiated grade showed poor survival. Therefore, public awareness about tobacco control for OCC prevention and earlier diagnosis of OCC is urgently needed in our Pakistani population.

Background/Objectives: Chronic inflammation significantly contributes to human malignancies. We investigated the prognostic significance of the preoperative modified systemic inflammation score (mSIS) in patients with primary oral cavity squamous cell carcinoma (OCSCC). Methods: We retrospectively reviewed data from 320 OCSCC patients who underwent curative surgery between 2007 and 2017. Based on preoperative lymphocyte-to-monocyte ratio (LMR) and serum albumin levels, patients were classified into three groups: mSIS = 2 (LMR < 3.4 and albumin < 4.0 g/dL), mSIS = 1 (LMR < 3.4 or albumin < 4.0 g/dL), and mSIS = 0 (LMR ≥ 3.4 and albumin ≥ 4.0 g/dL). We explored the associations between the preoperative mSIS and overall survival (OS) and disease-free survival (DFS). We developed a nomogram based on mSIS for OS prediction. Results: The distribution was mSIS = 0 (n = 197, 61.6%), mSIS = 1 (n = 99, 30.9%), and mSIS = 2 (n = 24, 7.5%). Kaplan–Meier estimated OS and DFS for the mSIS = 0, mSIS = 1, and mSIS = 2 groups demonstrated a sequential decrease (both p < 0.001). The prognostic significance of mSIS was consistent across subgroup analyses. Multivariable analysis revealed that mSIS = 1 and mSIS = 2 were independent negative prognostic indicators. The mSIS-based nomogram effectively predicted OS (concordance index: 0.755). Conclusions: The mSIS reliably predicts OS and DFS in OCSCC patients undergoing surgery, with the nomogram providing individualized OS estimates, enhancing mSIS's clinical utility. [ABSTRACT FROM AUTHOR]

Background and Aim: Oral and esophageal cancers are globally prevalent, especially in East Asia. Over half of head and neck cancer patients developing second primary esophageal cancer (SPEC) were initially diagnosed with oral cavity cancer (OCC). This study assessed the cost‐effectiveness of universal endoscopic screening for early SPEC prevention in newly diagnosed OCC patients at different stages. Methods: This study employed Markov cohort models to evaluate the cost‐effectiveness of endoscopic SPEC screening post‐OCC diagnosis (stages 0 to IV) between screened and non‐screened groups. Four surveillance frequencies were assessed: (i) one time, (ii) annual for 3 years, (iii) annual for 10 years, and (iv) annual for life. A hypothetical cohort of 100 000 cases across stages was compared for costs and quality‐adjusted life‐years (QALYs), discounted annually at 3%. Results: All four screening strategies were beneficial for all OCC stages, especially for early‐stage patients, resulting in higher QALYs. Lifetime/annual screening from the payer's perspective proved most favorable, with incremental QALYs of 1.23 at stage 0 and 0.06 at stage IV. Incremental costs for this strategy ranged from NTD 121 331 (USD 4044) at stage 0 to NTD 13 032 (USD 434) at stage IV. Both incremental costs and incremental cost‐effectiveness ratio (ICER) values indicated cost savings from a societal perspective. The ICER values ranged from NTD −626 440 (USD −20 881) at stage 0 and NTD −475 021 (USD −15 834) at stage IV. Conclusions: Overall, our study provided cost‐effectiveness evidences to understanding the cost‐effectiveness of endoscopic screening in OCC patients, particularly emphasizing the benefits of early and consistent screening. [ABSTRACT FROM AUTHOR]

Background/Objectives: Oral cavity squamous-cell carcinoma is among the most frequent head and neck neoplasms. Early-stage T1/T2N0 accounts for 40/45% of new diagnoses. Of these, about 30% of cases hide occult metastases in the neck. The management of clinically N0 neck is of paramount importance and is still being debated. Methods: The medical records of patients with a clinical diagnosis of early-stage T1-T2N0 carcinoma of the oral cavity between 2011 and 2021 were retrospectively analysed. The inclusion criteria were complete medical and radiological records, pT1-2 pathology staging, and a minimum follow-up of 24 months. Biographical, management, and survival data were analysed using IBM SPSS Statistics [28.0.1.1]; IBM Corp., Armonk, NY, USA). Results: A total of 121 patients met the inclusion criteria. The tongue was the most affected site, with 52 cases. All patients underwent resection of the primary tumour; for neck management, 47 (38.8%) underwent elective neck dissection, 36 underwent follow-up, and 11 underwent sentinel lymph node biopsy. A total of 59 cases were staged as T1 and 62 as T2; in 97 (80.2%) cases, the neck was confirmed as N0; in 10 (8.3%), N1; in 1 case, N2a; in 8, N2b; in 2, N2c; and in 3, N3b. The mean DOI was 4.8 mm. In a Cox regression, a statistically significant association was shown between overall survival and pN staging (p < 0.05). Kaplan–Meier analysis showed a statistically significant difference between different regimens of management of the neck in terms of overall survival, disease-free survival, and disease-specific survival in favour of elective neck dissection and sentinel lymph node biopsy compared to watchful policy (p < 0.05). Conclusions: Elective neck dissection and sentinel lymph node biopsy proved to be safe and oncologically effective in the treatment of clinically N0 early-stage oral carcinoma. [ABSTRACT FROM AUTHOR]

Background: Oral cavity cancer (OCC) represents a significant public health burden in South Asia, ranking as the most prevalent cancer affecting males in Pakistan and contributing considerably to morbidity and mortality. The objective of this study was to evaluate the survival rates in patients diagnosed with OCC in the Pakistani population and identify the factors influencing survival. Methods: This was a retrospective cohort study conducted at the Aga Khan University Hospital Karachi, Pakistan. A total of 2238 cases diagnosed with OCC from May 2011 through December 2020, who met the inclusion criteria, were included. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Adjusted hazard ratios (HR) and their 95% confidence intervals (CIs) were estimated using a Cox regression model to identify the factors significantly influencing survival. Results: Among all cases, 54.0% were diagnosed in individuals 50 years of age and below and 73.0% were tobacco users. Overall survival, 1-year, 3-year, and 5-year survival rates were 54.9%, 88.9%, 81.6%, and 75.9% respectively. After adjustment for all the significant confounding and prognostic factors, age was an important factor showing that adults > 50 years had poorer survival compared to ≤ 50 years (HR = 1.43, 95% CI = 1.11–1.83). Poorly differentiated grade of OCC compared to well-differentiated grade (HR = 2.49, 95% CI = 1.61–3.84) and stage IV compared to earlier stages (HR = 3.56, 95% CI = 2.13–5.94) were also associated with poor survival. Conclusion: Notably, there was a high occurrence of late stage (III and IV) OCC in individuals aged ≤ 50 years, with the buccal mucosa being the most common site involved. Moreover, a large proportion of our patients had a history of tobacco use. Patients with advanced-stage disease and poorly differentiated grade showed poor survival. Therefore, public awareness about tobacco control for OCC prevention and earlier diagnosis of OCC is urgently needed in our Pakistani population. [ABSTRACT FROM AUTHOR]

Introduction: This study provides an epidemiological description of cancer in the lip, oral cavity, and oropharynx in the South and South‐East Asia region. Methods: The number of new cases and deaths was extracted from the GLOBOCAN 2020 and the CI5 series. We present age‐standardized incidence and mortality rates per 100,000 inhabitants. To assess temporal trends, we estimated the annual percent change. Results: The incidence rates (ASR) for lip and oral cavity cancer in South and South‐East Asia were highest in Taiwan (30.2), Sri Lanka (16.5), India (14.8), and Pakistan (13.2) among males. For oropharyngeal cancer, the highest rates were found in Taiwan (4.7), Bangladesh, Sri Lanka, and India (4.3, 2.9, and 2.6, respectively). Incidence rates were consistently higher in males compared to females. Overall, trends in lip and oral cavity cancer incidence were either stable or decreasing in most of the populations evaluated. In India, an increase in rates among males contrasted with a decline among females over the study period. Conclusion: Incidence and mortality rates of oral cavity cancer in South and South‐East Asia are among the highest globally. Our results suggest an optimistic trend of reduction in oral cavity rates in the region, despite an increase in rates among Indian males. [ABSTRACT FROM AUTHOR]

Objective: Oral cavity is one of the common site of cancer in head and neck. They have high cure rate but locoregional failure seen in some cases at primary, nodal or metastatic site. We retrospectively analysed treatment results of oral cavity cancer in our institute and intented to define the prevalence and pattern of failure. Materials and Methods: It is a prospective cohort study. 179 cases of post operative oral cavity cancer between January 2019 to December 2021, who took radiotherapy or chemoradiotherapy treatment in our institute were studied. 79 patients had loss of follow up during and after treatment. Results of study excluded these patients. Results: Median follow up was 24 months (8-40 months). Treatment failure after radiotherapy or chemoradiotherapy at primary site and at nodal site was 22 % and 2 % respectively. In 8% cases recurrence was present at both primary and nodal site. Metastasis at extra nodal site occurred in 4% cases (3% in liver, 1% in bone). Conclusion: Operated case of oral cavity cancer when treated with radiotherapy or chemoradiotherapy has very high cure rate and few locoregional failures at primary and nodal site and rarely at distant site. Recurrence most commonly seen in advanced disease. Therefore, advanced disease patients should be treated with more aggressive treatment to achieve higher cure rate in oral cavity cancer patients. Disease free survival and overall survival was better in early stage than in advanced stage. Node positive disease had more risk of recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Introduction: The routine assessment of intraoperative margins has long been the standard of care for oral cavity cancers. However, there is a controversy surrounding the best method for sampling surgical margins. The aim of our study is to determine the precision of a new technique for sampling tumor bed margins (TBMs), to evaluate the impact on survival and the rate of free flap reconstructions. Methods: This retrospective cohort study involved 156 patients with primary cancer of the tongue or floor of the mouth who underwent surgery as initial curative treatment. Patients were separated into 2 groups: one using an oriented TBM derived from Mohs' technique, where the margins are taken from the tumor bed and identified with Vicryl sutures on both the specimen and the tumor bed, and the other using a specimen margins (SMs) driven technique, where the margins are taken from the specimen after the initial resection. Clinicopathologic features, including margin status, were compared for both groups and correlated with locoregional control. Precision of per-operative TBM sampling method was obtained. Results: A total of 156 patients were included in the study, of which 80 were in TBM group and 76 were in SM group. Precision analysis showed that the oriented TBM technique pertained a 50% sensitivity, 96.6% specificity, 80% positive predictive value, and an 87.5% negative predictive value. Survival analysis revealed nonstatistically significant differences in both local control (86.88% vs 83.50%; P =.81) as well as local-regional control (82.57% vs 72.32%; P =.21). There was a significant difference in the rate of free flap-surgeries between the 2 groups (30% vs 64.5%; P <.001). Conclusion: Our described oriented TBM technique has demonstrated reduced risk of free flap reconstructive surgery, increased precision, and similar prognostic in terms of local control, locoregional control, and disease-free survival when compared to the SM method. [ABSTRACT FROM AUTHOR]

Background: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC). Methods: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease‐free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable. Results: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72–1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70–1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87–1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83–1.11, p = 0.58). Conclusion: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC. [ABSTRACT FROM AUTHOR]

(1) Background: Oral cavity cancer represents the most common site of origin of head and neck mucosal malignancies. A few limited studies have suggested that chronic irritation, particularly in non-healing ulcers, and fibrotic tissue from poor dentition or ill-fitting dentures had a role in developing mouth cancer. This scoping review aims to evaluate the existing evidence concerning Oral Cavicty Cancer (OCC) in non-smokers/non-drinkers and the relationship with dental trauma. (2) Methods: A scoping review of the PubMed, Embase, and Web of Science databases was completed in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. (3) Results: Of the 33 articles that met inclusion, in 6 of them authors discussed the role of topography in dental trauma, in 11 articles authors discussed the carcinogenesis mechanism involved in chronic mucosal trauma, in 17 articles data on ill-fitting dentures was included, 4 studies dealt with the effect of broken/sharp teeth on mucosal damage, and in 7 studies the role of oral hygiene was covered. Less frequently discussed topics included gender, risk of neck nodes, and the role of potentially malignant oral disorders. (4) Conclusions: The available literature suggests a potential connection between chronic dental trauma and the development of OCC. Studies have highlighted factors such as denture use and ill-fitting dental appliances as contributors to an increased risk of oral cancer. Interestingly, we still miss data to support the hypothesis that women, particularly those without toxic habits like smoking or alcohol consumption, appear to be disproportionately affected by oral cancer related to chronic dental trauma. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to calculate the burden of oral cavity cancer (OCC) including incidence, mortality rate, survival rate, and influence of predictive factors such as clinicopathological, demographic findings, and treatment modalities. Materials and Methods: Data in this retrospective study were collected from India's population-based cancer registry (PBCR) from 2010 to 2016. A total of 1051 cases of OCC were noted. Incidence and mortality rates were calculated. The cumulative survival outcome was calculated using Kaplan–Meier (KM) method. Prognostic factors were estimated using the Cox proportional hazard regression model. Results: The age-standardized incidence rates (ASR), and mortality rate (ASMR), of overall OCC cases were 10.1 and 8.4 per 100 thousand population, respectively. Five-year overall survival (OS) was 32.3%. Survival outcome was significantly associated with the given treatment (Chi-square value = 58.17, P = 0.0001) and anatomical site (Chi-square value = 26.70, P = 0.0001). 17.6% of cases in males were <39-year age group. The hazard ratio (HR) in the age group of >50 years was 2.065 (95% CI 1.34-3.18, P = 0.001). Combination therapy had an HR of 2.630 (95% CI 1.91-3.63, P value 0.000). Tonsillar carcinoma (C09) (95% CI 1.04-3.12) had 1.8 times more chances of death than lip carcinoma (C00). Conclusion: OCC cases are increasing in the younger population, and overall, cases show higher mortality rates with reduced survival outcomes. Prognostic factors such as age >50 years, single modality treatment, and alveolar and tonsillar malignancy are associated with poor survival. OCC robust screening by a trained health professional can improve early detection and increases awareness and lower mortality of the disease. [ABSTRACT FROM AUTHOR]

Background: The current standard-of-care pathology report relies only on lengthy written text descriptions without a visual representation of the resected cancer specimen. This study demonstrates the feasibility of incorporating virtual, three-dimensional (3D) visual pathology reports to improve communication of final pathology reporting. Materials and methods: Surgical specimens are 3D scanned and virtually mapped alongside the pathology team to replicate grossing. The 3D specimen maps are incorporated into a hybrid visual pathology report which displays the resected specimen and sampled margins alongside gross measurements, tumor characteristics, and microscopic diagnoses. Results: Visual pathology reports were created for 10 head and neck cancer cases. Each report concisely communicated information from the final pathology report in a single page and contained significantly fewer words (293.4 words) than standard written pathology reports (850.1 words, p

ObjectivesThe purpose of the study was to assess the impact of a pretherapeutic Multidisciplinary Tumor Board (MTB) presentation on the prognosis and treatment outcomes in patients with primary oral cavity carcinoma.Materials and methodsThis single-center study included 630 patients diagnosed with oral cavity carcinoma treated between 2010 and 2020. The study cohort was divided in a group with and without pretherapeutic MTB presentation. Data on patient demographics, tumor characteristics, treatment and the time to treatment initiation (TTI) were collected retrospectively.ResultsPrimary findings revealed no significant difference in 3-year survival rate (3-YSR) and 3-year disease-free survival rate (3-YDFSR) for the non-MTB and MTB group. The 3-YSR was 73.1% in the non-MTB group and 67.1% in the MTB group (p = 0.112). The 3-YDFSR was 73.8% in the non-MTB group and 76.5% in the MTB group (p = 0.447). Estimated mean 5-year survival (5-YS) and 5-year disease-free survival in (5-YDFS) did not differ significantly between both groups, across the UICC stages I-IV, as well as for the entire cohort. The TTI was significantly longer in the MTB group (33.5 days, CI: 31.3;35.7) compared to the non-MTB group (20.1 days, CI: 17.9;22.4, p

AbstractMirtazapine is a selective serotonergic antidepressant that functions by blocking adrenergic alpha2-autoreceptors and heteroreceptors and inhibiting 5-HT2 and 5-HT3 receptors. It is a noradrenergic drug. Mirtazapine has anxiolytic or sleep-quality-improving effects, aggravates appetite-stimulation, and has stomach emptying functions. When treating poly-symptoms such as appetite loss, anxiety, depression, nausea, and sleeplessness off-label, mirtazapine is being used more and more. A not so common side effect of mirtazapine medication is peripheral edema. The ensuing case study will demonstrate how peripheral edema is an uncommon mirtazapine adverse effect. Peripheral edema was observed in a patient with advanced oral cavity cancer three days after starting a daily dose of 15 mg of mirtazapine for polysymptomatology. The peripheral edema completely resolved after stopping mirtazapine. To the best of our knowledge, this is the first instance of a patient with advanced oral cavity cancer experiencing peripheral edema as a result of receiving mirtazapine medication. Our study will assist medical professionals in identifying the potential use of mirtazapine in situations where peripheral edema develops quickly, facilitating its quick clearance. [ABSTRACT FROM AUTHOR]

This study employs a two-sample bidirectional Mendelian randomization (MR) approach to systematically evaluate the causal relationship between gut microbiota and oral cavity cancer (OCC). Objective: To address the challenge in establishing the causal relationship between gut microbiota and OCC, we applied a systematic MR analysis. Methods: Utilizing GWAS data from the MiBioGen consortium (18,340 individuals) and UK Biobank (n = 264,137), we selected instrumental variables and employed MR-Egger, weighted median, IVW, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using Cochran's Q test and MREgger intercept test. Results: Our findings indicate, at the order level, Bacteroidales (OR = 0.9990, 95% CI = 0.9980-1.0000, P = 0.046), Burkholderiales (OR = 1.0009, 95% CI = 1.0001-1.0018, P = 0.033), and Victivallales (OR = 0.9979, 95% CI = 0.9962-0.9995, P = 0.037) exhibit causality on OCC in the Weighted median, IVW, and MR-Egger analyses, respectively. At the family level, Alcaligenaceae (OR = 1.0012, 95% CI = 1.0004-1.0019, P = 0.002) and Clostridiaceae1 (OR = 0.9970, 95% CI = 0.9948-0.9992, P = 0.027) show causality on OCC in IVW and MR-Egger analyses. At the genus level, Clostridiumsensustricto1 (IVW, OR = 0.9987, 95% CI = 0.9980-0.9995, P = 0.001; MR-Egger, OR = 0.9978, 95% CI = 0.9962-0.9995, P = 0.035), Desulfovibrio (IVW, OR = 1.0008, 95% CI = 1.0001-1.0015, P = 0.016), Eggerthella (IVW, OR = 0.9995, 95% CI = 0.9990-1.0000, P = 0.048), Eubacterium fissicatena group (IVW, OR = 1.0005, 95% CI = 1.0000-1.0009, P = 0.032), and Holdemanella (IVW, OR = 0.9994, 95% CI = 0.9989-0.9999, P = 0.018) are implicated in causing OCC in related analyses. Conclusion: Our study identifies Burkholderiales order, Alcaligenaceae family, Desulfovibrio genus, and Eubacterium fissicatena group as causally increasing OCC risk. In contrast, Bacteroidales order, Victivallales order, Clostridiaceae1 family, Clostridiumsensustricto1 genus, Eggerthella genus, and Holdemanella genus are causally associated with a decreased OCC risk. However, further investigations are essential to delineate an optimal gut microbiota composition and unravel the underlying mechanisms of specific bacterial taxa in OCC pathophysiology. [ABSTRACT FROM AUTHOR]

Introduction In head and neck cancer (HNC) patients, fatigue is present throughout the course of treatment and during follow-up. Cancer-related fatigue (CRF) is a significant treatment-related side effect experienced by oral cancer patients during and after treatment. CRF, when coupled with other side effects of oral cavity cancer, patients who undergo definitive treatment have some of the most dramatic acute side effects, and reduced overall quality of life (QoL). Although there are upcoming intervention strategies to manage CRF, the effect of exercise intervention is explored in this study. The rationale for considering exercise to manage CRF is that it may alleviate the combined effect of toxic treatment and decreased levels of activity during the treatment that reduces the capacity for physical performance. Objective This study was conducted to investigate the effectiveness of exercise intervention on CRF, and its influence on functional capacity and QoL among patients with oral cavity cancer during and after their primary cancer treatment. Materials and Methods Oral cavity cancer patients (n = 223), planned for only chemoradiotherapy with curative intent were screened for CRF. Based on the inclusion criteria, 69 patients were grouped randomly into experimental (n = 35) and control (n = 34) groups. Patients in the experimental group were provided structured exercise intervention, while the control group was offered standard and routine care. Structured exercise in this present study comprised moderate-intensity walking and resistance exercises using TheraBand every day for three to five times a week. CRF was assessed using symbolic assessment of fatigue extent and the functional capacity was assessed by 6-minute walk test (6MWT), maximal oxygen uptake (VO 2max), and hand dynamometer. QoL was assessed using the European Organization for Research and Treatment for Cancer-QoL (EORTC QLQ-C30) and the Head and Neck Cancer module (HN35), while distress was assessed by the National Comprehensive Cancer Network (NCCN) Distress Thermometer. Randomized patients were assessed at four points. Result The size effects in fatigue extent (η p2 = 0.40) and fatigue impact (η p2 = 0.41) were found to be moderate, and a positive correlation between 6MWT, fatigue extent, and fatigue impact was observed. Conclusion This study suggests that exercise intervention has a significant positive impact on CRF, most aspects of QoL, and the functional capacity of the patients. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies have provided evidence suggesting an association between Alzheimer’s disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear. Methods: In order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652). Results: We identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63–0.92, p = 3.73 × 10−3). In the opposite direction, oral conditions were not causally associated with risk of AD. Conclusion: The present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. Methods: A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. Results: The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (β = -1.013). The secondary outcomes confirmed the results (all β < 0) and all assessments supported the robustness, too (all p > 0.05). Conclusion: The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended. [ABSTRACT FROM AUTHOR]

Adequate surgical margins are essential in oral cancer treatment, this is, however, difficult to appreciate during training. With advances in training aids, we propose a silicone-based surgical simulator to improve training proficiency for the ablation of oral cavity cancers. A silicone-based tongue cancer model constructed via a 3D mold was compared to a porcine tongue model used as a training model. Participants of varying surgical experience were then asked to resect the tumors with clear margins, and thereafter asked to fill out a questionnaire to evaluate the face and content validity of the models as a training tool. Eleven participants from the Otolaryngology-Head and Neck Surgery unit were included in this pilot study. In comparison to the porcine model, the silicone model attained a higher face (4 vs. 3.6) and content validity (4.4 vs. 4.1). Tumor consistency was far superior in the silicone model compared to the porcine model (4.1 vs. 2.8, p = 0.0042). Fellows and staff demonstrated a better margin clearance compared to residents (median 3.5 mm vs. 1.0 mm), and unlike the resident group, there was no incidence of positive margins. The surgical simulation was overall useful for trainees to appreciate the nature of margin clearance in oral cavity cancer ablation. [ABSTRACT FROM AUTHOR]

Objective: Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. Data Sources: The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. Review Methods: Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease‐specific survival (DSS), disease‐free survival (DFS), and locoregional control (LRC). Results: About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non‐significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38–2.69), DSS (HR: 2.03; 95% CI: 0.54–7.56), and LRC (HR: 0.89; 95% CI: 0.53–1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77–0.97). Conclusion: The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. Level of Evidence: NA Laryngoscope, 134:2019–2027, 2024 [ABSTRACT FROM AUTHOR]

Background: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6–14 days post‐operatively due to concern for orocutaneous fistula development. Methods: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed‐ and random‐effects meta‐analyses were used. Results: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = −0.02, p = 0.06) or free flap failure (RD = −0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = −2.43, p < 0.01). Conclusions: While further prospective trials are necessary, initiation of oral intake before post‐operative day 5 may be appropriate in properly selected patients following oral reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). Methods: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19–88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50–66) administered in 30 fractions (range 25–33). Results: Median follow-up time was 73 months (range 24–147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). Conclusion: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC. [ABSTRACT FROM AUTHOR]

Background and purpose: The volume treated with postoperative radiation therapy (PORT) in patients with oral cavity squamous cell carcinoma (OCSCC) is a mediator of toxicity affecting quality of life. Current guidelines only allow for very limited reduction of PORT volumes. This study investigated the safety and efficacy of de-intensified PORT for patients with OCSCC by refined compartmentalization of the treatment volume. Materials and methods: This retrospective cohort study identified 103 OCSCC patients treated surgically from 2014 to 2019 with a loco-regional risk profile qualifying for PORT according to guidelines. PORT was administered only to the at-risk compartment and according to a refined compartmentalization concept (CC). Oncological outcome of this CC cohort was compared to a historical cohort (HC) of 98 patients treated before the CC was implemented. Results: Median follow-up time was 4.5 and 4.8 years in the CC and HC cohorts, respectively. In the CC cohort, a total of 72 of 103 patients (70%) had a pathological risk profile that allowed for further compartmentalization and, hence, received a reduced treatment volume or omission of PORT altogether. Loco-regional control at 3 and 5 years was 77% and 73% in the CC cohort versus 78% and 73% in the HC (p = 0.93), progression-free survival was 72% and 64% versus75% and 68% (p = 0.58), respectively. Similarly, no statistically significant difference was seen in other outcome measures. Conclusions: De-intensified PORT limiting the treatment volume to the at-risk compartment or avoiding PORT altogether for low-risk patients with OCSCC does not seem to compromise disease control in this retrospective comparison. Based on these hypothesis-generating findings, a prospective study is being planned. [ABSTRACT FROM AUTHOR]

Abstract Background While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. Methods This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. Results MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p

AbstractHigher tobacco and alcohol use have led to a consistent increase in head and neck cancer incidence rates. Currently employed chemotherapeutic and surgical treatment are associated with significant drawbacks. Herein, we evaluated the anti-tumour effect of gold nanoparticles as a vehicle for the delivery of a triple chemotherapy drug formulation and elucidated the potential underlying mechanism. The hydrodynamic size of docetaxel, cisplatin, and 5-fluorouracil physically co-adsorbed on Au nanoparticles was 56 ± 0.8 nm, showing a negative zeta potential. Fourier transform infra-red spectroscopy data confirmed that the triple chemotherapy drug successfully interacted with the gold nano-carrier. Au nanoparticles exhibited high loading efficacy of docetaxel (61%), cisplatin (75%), and 5-fluorouracil (90%), with a controlled drug release profile at 24 h. The triple chemotherapy drug formulation was tested in human oral cavity cancer cell line (KB). Cytotoxicity achieved through a synergistic effect between the treatments led to apoptosis, with a lower half-maximal inhibitory concentration indicating higher cytotoxicity than that of plain docetaxel-cisplatin-fluorouracil. Taken together, we demonstrated that the docetaxel-cisplatin-fluorouracil-gold complex exhibited excellent cytotoxicity in KB cells, superior to that docetaxel-cisplatin-fluorouracil.HIGHLIGHTSThe docetaxel-cisplatin-fluorouracil-Au complex showed a controlled drug-release profile at 24 h.The docetaxel-cisplatin-fluorouracil-Au complex exhibited enhanced internalisation efficiency in cells.Au nanoparticles were biocompatible, with no change in apoptosis among cell line.Spherical Au nanoparticles allowed a high volume of incorporated docetaxel, cisplatin, and 5-fluorouracil to steadily attach onto cells.

Pain has a certain number of physical, psychological and social consequences. Pain is of particular importance in the postoperative period for patients with tumors of the oral cavity and of the oropharynx. The effectiveness of analgesia in the postoperative period is a serious problem in maxillofacial surgery. Postoperative pain is not always removable, sometimes it becomes chronic. Pronounced pain syndrome in the postoperative period is experienced by 40 to 75% of patients, but 50% of patients experience pain of medium and high intensity. The aim of this study was a comparative assessment of the effectiveness of a new alternative method of a long-term postoperative regional analgesia and the use of non-narcotic analgesics in patients with tumors of the oral cavity and oropharynx in the postoperative period. The study was conducted in 48 patients (38 men, 10 women, average age 58,05±12,31 years) with tumors of the oral cavity and oropharynx. Patients were divided into two groups depending on the method of postoperative analgesia. In the main group (22 patients) pain was suppressed by a long-term postoperative regional analgesia. In the control group (26 patients) analgesia was performed with non-narcotic analgesics. To control the effectiveness of analgesia, a visual analog scale was used, the duration of analgesia and the manifestation of dysphagia on the day 1, 3 and 10 after surgical intervention as well as similar effects were assessed. On the day 10 of using a long-term postoperative regional analgesia, a positive trend towards a reduction in pain syndrome was observed (2.0±0.63), in contrast to drugs of general action (p

Abstract Background The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers. Methods Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn’s disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results. Results IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P

Abstract Objective To determine the overall surgical outcomes of infranotch T4b oral cancers and compare them with T4a oral cancers. Methods PubMed, EMBASE and Cochrane databases from 2000 to 2022 were systematically searched. Clinical studies reporting at least one outcome following curative surgery and adjuvant therapy for comparison of patients with either infranotch T4b (IN–T4b) or T4a tumour. The heterogeneity of the included studies was determined using Tau-squared, Chi-squared, and the Higgins I 2 test. The random effects model was used to determine the log odds ratio (logOR). Results The systematic review comprised 11,790 patients from 16 included studies. Seven studies were included in the meta-analysis (n = 11,381). For IN–T4b patients, the pooled 2 and 5 year overall survival (OS) were 59.3% and 53.2%, 2 and 5 year disease-free survival (DFS) 57.9% and 48.4%, 2 and 5 year disease-specific survival (DSS) 72% and 68%, and 2 and 5 year local control (LC), 47% and 56%, respectively. There was no statistically significant difference in 2 year OS [logOR = 0.28 (−0.47, 1.03), p = 0.46, confidence interval (CI) = 95%], 5 year OS [logOR = 0.7 (−0.4, 1.8), p = 0.54, CI = 95%], 2 year DFS [logOR = 0.22 (−0.35, 0.79), p = 0.45, CI = 95%], 5 year DFS [logOR = 0.17 (−0.42, 0.77), p = 0.57, CI = 95%], 2 year LC [logOR = 0.47 (−0.33, 1.26), p = 0.25, CI = 95%] and 5 year LC [logOR = 0.34 (−0.31, 0.99), p = 0.31, CI = 95%] between IN–T4b and T4a oral cancers. Conclusion Results of this meta-analysis suggest that IN–T4b oral cancers have similar outcomes to T4a oral cancers, which supports down-staging IN–T4b cancers to T4a cancers.

Background: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. Methods: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. Results: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007–1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005–1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147–1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139–1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. Conclusion: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association. [ABSTRACT FROM AUTHOR]

Backgrounds: We aimed to clarify the outcomes of postoperative radiotherapy (PORT) after salvage neck dissection for cervical lymph node (LN) recurrence in oral cavity cancer. Methods: We retrospectively evaluated overall survival (OS), recurrence‐free survival (RFS), recurrence patterns, and adverse events of 51 patients with high‐risk features receiving PORT after salvage neck dissection between 2009 and 2019. Results: After a median follow‐up of 7.4 years from PORT initiation, the 7‐year OS and RFS rates were 66.3% (95% CI: 54.0–81.3) and 54.6% (95% CI: 42.1–70.9), respectively. Age <70 years and isolated LN recurrence were significantly associated with longer OS and RFS. Among the 22 patients who experienced recurrence, 14 experienced recurrence within the radiation field. PORT‐related grade 3 acute mucositis (35%) and late adverse events (osteoradionecrosis [4%] and laryngeal stenosis [2%]) were observed. Conclusions: PORT after salvage neck dissection for cervical LN recurrence achieved good survival with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the prognostic utility of the preoperative platelet‐to‐albumin ratio (PAR) among patients with oral cavity squamous cell carcinoma (OSCC). Methods: We retrospectively reviewed of 355 patients with surgically‐treated OSCC between 2008 and 2017. The optimal PAR cutoff for patient stratification was determined through X‐tile analysis. Prognostic variables for disease‐free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards models. We developed a PAR‐based nomogram to predict personalized OS. Results: We determined the optimal PAR cutoff to be 7.45. A PAR of ≥7.45 was an independent negative prognostic factor for DFS and OS (hazard ratio = 1.748 and 2.386; p = 0.005 and p < 0.001, respectively). The developed nomogram demonstrates the practical utility of PAR and accurately predicts personalized OS. Conclusions: The preoperative PAR is a promising and cost‐effective prognostic biomarker for patients with surgically‐treated OSCC; the PAR‐based nanogram accurately predicts OS for such patients. [ABSTRACT FROM AUTHOR]

Background: Treatment for resectable oral cavity cancer (OCC) often includes combinations of surgery and radiotherapy (RT), but there is no conclusive information on the preferred treatment order. The aim of this study was to assess the costs and cost-effectiveness of two alternative treatment regimens for patients with OCC, reflecting pre- and post-operative RT, from a societal perspective. Methods: The study used data from the ARTSCAN 2 randomised controlled trial, which compares pre-operative accelerated RT with post-operative conventionally fractionated RT. Two-hundred-forty patients were included in the analysis of treatment outcomes. Direct costs were retrieved from the hospital's economic systems, while indirect costs were obtained from national registries. Cost-effectiveness was assessed and a sensitivity analysis was performed. Overall survival (OS) at 5 years, was used as effect measure in the analysis. Results: Two-hundred-nine patients completed the treatments and had retrievable data on costs. Mean direct costs (inpatient and outpatient care) were € 47,377 for pre-operative RT and € 39,841 for post-operative RT (p = 0.001), while corresponding indirect costs were € 19,854 and € 20,531 (p = 0.89). The incremental cost, i.e., the mean difference in total cost between the treatment regimens, was € 6859 paralleled with a 14-percentage point lower OS-rate at 5 years for pre-operative RT (i.e., 58 vs. 72%). Thus, pre-operative RT was dominated by post-operative RT. Conclusions: From a societal perspective, post-operative RT for patients with resectable OCC is the dominant strategy compared to pre-operative RT. [ABSTRACT FROM AUTHOR]