Search

Purpose: To assess the antioxidant and antineoplastic effects of Hibiscus sabdariffa Linn. on oral squamous cell carcinoma cells. Materials and Methods: Human squamous cell carcinoma HSCC cells were tested for cytotoxicity by a methanol extract of Hibiscus sabdariffa (MEHSP). After 24, 48, and 72 h, the MTT assay and Trypan blue exclusion test were used to determine cell survival and death. 2, 2-diphenyl-1-picrylhydrazyl (DPPH), DNA Protection Assay (DPA), and ferric reducing antioxidant power assay (FRAPA) measured the antioxidant activity of MEHSP. Results: The antioxidant activity (%) ranged from 47.92-82.24 in the DPPH test, 11.61-73.65 in the DPA, and 4.97-52.09 in the FRAPA. The HSCC in-vitro cytotoxicity assay showed dose- and time-dependent cell viability. MEHSP at 5 μg/ml inhibited viable cells, while increasing MEHSP doses decreased cell viability. The Trypan blue exclusion test showed that MEHSP significantly reduced cell viability at 24, 48, and 72 h. Conclusion:Hibiscus sabdariffa contains antioxidant and HSCC-cytotoxic properties. [ABSTRACT FROM AUTHOR]

Purpose: To screen for the cisplatin resistance-related prognostic signature in oral squamous cell carcinoma (OSCC) and assess its correlation with the immune microenvironment. Materials and Methods: The gene expression data associated with OSCC and cisplatin-resistance were downloaded from TCGA and GEO databases. Cisplatin-resistant genes were selected through taking the intersection of differentially expressed genes (DEGs) between tumor and control groups as well as between cisplatin-resistant samples and parental samples. Then, prognosis-related cisplatin-resistant genes were further selected by univariate Cox regression and LASSO regression analyses to construct a survival prognosis model. A GSEA (gene set enrichment analysis) between two risk groups was conducted with the MSigDB v7.1 database. Finally, the immune landscape of the sample was studied using CIBERSORT. The IC50 values of 57 drugs were predicted using pRRophetic 0.5. Results: A total 230 candidate genes were obtained. Then 7 drug-resistant genes were selected for prognostic risk-score (RS) signature construction using LASSO regression analysis, including STC2, TBC1D2, ADM, NDRG1, OLR1, PDGFA and ANO1. RS was an independent prognostic factor. Additionally, a nomogram model was established to predict the 1-, 2-, and 3-year survival rates of samples. The GSEA identified several differential pathways between two risk groups, such as EMT, hypoxia, and oxidative phosphorylation. Fifteen immune cells were statistically significantly different in infiltration level between the two groups, such as macrophages M2, and resting NK cells. A total of 57 drugs had statistically significantly different IC50 values between two risk groups. Conclusion: These model genes and immune cells may play a role in predicting the prognosis and chemoresistance in OSCC. [ABSTRACT FROM AUTHOR]

PurposeWe investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities.MethodsNon-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC).ResultsThis study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and thiazides (RR = 1.10, 95% CI = 1.04-1.16); for squamous cell carcinoma with calcium channel blockers (RR = 1.08, 95% CI = 1.01-1.14), diuretics (RR = 1.29, 95% CI = 1.17-1.43), and thiazides (RR = 1.36, 95% CI = 1.15-1.61); and for melanoma in angiotensin-converting enzyme inhibitors (RR = 1.09, 95% CI = 1.03-1.14), calcium channel blockers (RR = 1.08, 95% CI = 1.03-1.12), and thiazides (RR = 1.09, 95% CI = 1.02-1.17). The quality of evidence was low or very low. We observed evidence for dose-response for thiazides with basal cell carcinoma; angiotensin-converting enzyme inhibitors, diuretics, and thiazides with squamous cell carcinoma; and angiotensin-converting enzyme inhibitors, diuretics, and thiazides with melanoma. Our meta-analysis supports a potential causal association between some antihypertensives, particularly diuretics, and skin cancer risk.

Verruciform xanthomas are rare lesions affecting 0.025-0.5 of the population. They present as an asymptomatic, slow growing solitary lesion on the oral mucosa. Commonly misdiagnose as squamous cell carcinoma, verruca vulgaris, leukoplakia, and lichen planus. Presented is a 22 year old male with a painful verruciform xanthoma on the posterior ear lobe in a prior ear piercing. Keywords: Keloid, trauma-induced, verruciform xanthoma, Author(s): Hannah E. Myers (corresponding author) [1]; Subhapradha Rangarajan [2]; Michael Roberts [3,4]; Christopher Buckley [3,4]; Josh Hammel [3,4] Introduction Verruciform xanthomas are rare lesions affecting 0.025-0.5 of the population.[sup.[1]] [...]

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (sham). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p

Fistula-associated anal cancer in Crohns disease (CD) can be challenging to diagnose and treat. Patients with longstanding fistulas in the setting of CD who present with a sudden change in their symptoms should undergo biopsy under anesthesia with extensive sampling, followed by staging imaging. Pelvic magnetic resonance imaging (MRI) can be helpful in identifying the extent of the disease locally. Patients often present in the later stages due to the challenges associated with diagnosing these patients. Two subtypes of this disease include squamous cell carcinoma and adenocarcinoma, and treatment depends on diagnosis. Small sample size and lack of uniform data on treatments make it difficult to say which treatment modalities are optimal, but aggressive combined therapy is likely the best approach for survival. This will include chemotherapy and radiation and often radical resection as well. Despite this, survival is poor, although more recent data suggest that outcomes are improving.

The Main Problem Methods Results Conclusions Squamous cell carcinoma is the second most prevalent type of non–small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines.A novel new lung squamous cell carcinoma cell line, OMUL‐1, was developed from the primary lung cancer of a 74‐year‐old man. We assessed the characteristics and behavior of OMUL‐1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT‐PCR), and RNA sequencing and invasion assays.OMUL‐1‐an adherent cell line‐resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF‐1 was negative). An invasion assay demonstrated that OMUL‐1 had a lower invasion ability compared to that of other developed cell lines. RT‐PCR analysis and RNA sequencing indicated that OMUL‐1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c‐MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL‐1 cells. Immunohistochemistry revealed that IGF1R and PD‐L1 were expressed in both the primary and subcutaneous tumors.We developed a novel new squamous cell lung carcinoma cell line, OMUL‐1, that expresses IGF1R and PD‐L1. [ABSTRACT FROM AUTHOR]

Importance: Metastases to the submandibular gland (SMG) from oral cavity primaries are very rare. Hence, a gland-preserving level IB dissection technique is a feasible option without compromising the lymph node yield (LNY). Objective: To assess the feasibility and noninferiority of the SMG-preserving dissection technique to the conventional en bloc removal of level IB in terms of LNY in patients with cN0 oral squamous cell carcinoma (OSCC) undergoing elective neck dissection. Design: Parallel-design, single-center, open-label, randomized controlled trial. Setting: Tertiary care health care center—Department of Otorhinolaryngology-Head & Neck Surgery, AIIMS Rishikesh. Participants: Thirty-eight (n = 38) participants with 46 (n = 46) neck dissection specimens of OSCC were randomly allocated (1:1) into gland-preserving (n1 = 23) and en bloc (n2 = 23) dissection groups. Intervention: Elective neck dissection comparing SMG-sparing level IB dissection technique versus en bloc level IB dissection. Main Outcome Measures: LNY, lymph node density, and level IB operative time in both groups were compared between groups (α <.05). Results: Median LNY (P =.543) and lymph node density (P = 1.000) in level IB did not show significant differences between the groups. LNY in level IB by gland-preserving technique is also not inferior to the conventional en bloc dissection technique (mean difference = 0.217; 95% CI: [−0.597, 1.032]; P =.593). The mean level IB operative time is significantly longer in the gland-preserving group (P <.001). Conclusions and Relevance: None of the examined SMGs were involved by the tumor. SMG-preserving technique is noninferior to the traditional technique of level IB clearance and can be used in elective neck dissections without compromising the LNY. Functional neck dissection has greatly evolved to decrease patient morbidity, and this method can be adopted in case-specific situations. Trial registration: The trial was registered in the Clinical Trials Registry—India (CTRI/2022/05/042344) on May 2, 2023, https://ctri.nic.in/. [ABSTRACT FROM AUTHOR]

This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects. In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P <.001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P <.001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P =.003; median PFS, 14.2 vs 10.6 months; P =.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P <.001) and esophagitis (11.2% vs 2.4%, P =.006). The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis. [ABSTRACT FROM AUTHOR]

This study aims to examine the role of elective nodal irradiation (ENI) in clinically node-negative (cN0) sinonasal squamous cell carcinoma (SNSCC) and to define the optimal radiation fields for ENI. We retrospectively reviewed 368 patients with cN0 SNSCC treated between 2009 and 2021. The study evaluated the impact of ENI on overall survival, progression-free survival, regional failure–free survival, and distant metastasis–free survival, along with the coverage areas of ENI. The majority of patients underwent surgery (316/368, 85.9%), with 276 of 368 (75%) having tumors in the maxillary sinus or nasal cavity and 249 of 368 (67.7%) presenting with T4 disease. Additionally, in 119 of the 368 cases (32.3%), tumors were poorly differentiated. The 5-year overall survival, progression-free survival, regional failure–free survival, and distant metastasis–free survival rates were 59.3%, 54.0%, 57.6%, and 58.8%, respectively. ENI was performed in 217 patients (59%), with 16 experiencing neck relapse during follow-up. Although ENI did not enhance survival rates, it significantly reduced the overall regional failure rate (7.9% vs 1.8%; χ2 = 7.98; P <.01) and the cumulative incidence of regional failure (P =.045). Additionally, the subgroups with maxillary sinus origin (2.3% vs 13.5%; P =.025), T4 stage (1.8% vs 8.5%; P =.028), and poor differentiation (2.4% vs 13.5%; P =.029) had higher cumulative incidences of regional failure in patients without ENI. No significant difference was observed in survival and regional failure rates between patients treated with ENI to levels Ib and II with or without level III, as well as between cN0 patients with nonmidline crossing lesions receiving unilateral or bilateral ENI. Despite no survival benefit, ENI significantly decreases the regional failure rate in patients with cN0 SNSCC. For primary lesions not crossing the midline, ipsilateral ENI targeting levels Ib and II proves to be an effective strategy. [ABSTRACT FROM AUTHOR]

Background: Some pathogenic mechanisms suggest a potential relationship between gastroesophageal reflux disease (GERD) and respiratory diseases. However, evidence regarding the association between GERD and lung cancer is mixed. We aim to explore this relationship based on data from the large-scale UK Biobank study. Materials and methods: We performed a cross-sectional and prospective cohort study in 501,569 (45.58% male) individuals included in the UK Biobank at baseline (2006–2010). The Cox proportional hazards model and logistic regression models were used to assess the relationship between GERD and lung cancer, small cell lung cancer (SCLC), lung squamous cell carcinoma (LUSC), and lung adenocarcinoma (LUAD). Results: During a mean follow-up of 11.54 years, 3,863 (0.84%) incident lung cancer cases were identified. In the cross-sectional analysis using logistic models, significant associations were found between GERD and prevalent lung cancer cases (odds ratio [OR] = 1.87, 95% confidence interval [95% CI]: 1.45–2.38) and subtypes of lung cancer, with an OR (95% CI) of 3.19 (1.47–6.79) for SCLC, 2.08 (1.33–3.21) for LUSC, 1.85 (1.15–2.91) for LUAD. In the follow-up analysis using Cox models, GERD was associated with an increased risk of lung cancer (hazard ratio [HR] = 1.24, 95%CI: 1.14–1.34). Similar associations were also observed between GERD and SCLC (HR = 1.39, 95% CI: 1.09–1.78), LUSC (HR = 1.40, 95% CI: 1.18–1.65), and LUAD (HR = 1.17, 95% CI: 1.02–1.33). The risk of lung cancer resulting from GERD was mainly elevated in former smokers (HR = 1.38, 95% CI: 1.23–1.54) and current smokers (HR = 1.18, 95% CI: 1.04–1.34), but not in never-smokers (HR = 0.89, 95% CI: 0.70–1.14). No significant association was observed in former smokers who had quit smoking for at least 25 years. Conclusions: We found that GERD was positively associated with an increased risk of lung cancer, especially among smokers. Awareness of this association may be beneficial for prevention and treatment strategies of both diseases. [ABSTRACT FROM AUTHOR]

Background: To compare the performance of whole tumor and habitats-based computed tomography (CT) radiomics for predicting immunophenotyping in laryngeal squamous cell carcinomas (LSCC) and further evaluate the stratified effect of the radiomics model on disease-free survival (DFS) and overall survival (OS) of LSCC patients. Methods: In all, 106 LSCC patients (40 with inflamed and 66 with non-inflamed immunophenotyping) were randomly assigned into a training (n = 53) and testing (n = 53) cohort. Briefly, 750 radiomics features from contrast-enhanced CT images were respectively extracted from the whole tumor and two Otsu method-derived subregions. Intraclass correlation coefficients (ICCs) were calculated to evaluate the reproducibility. The radiomics models for predicting immunophenotyping were respectively created using K-nearest neighbors (KNN), logistic regression (LR), and Naive bayes (NB) classifiers. The performance of models in the testing cohort were compared using area under the curve (AUC). The prognostic value of the optimal model was determined by survival analysis. Results: The radiomics features derived from whole tumor showed better reproducibility than those derived from habitats. The best model for the whole tumor (LR classifier) showed superior performance than that for the habitats (KNN classifier) in the testing cohort, but there were no significant differences (AUC: 0.741 vs. 0.611, p = 0.112). Multivariable Cox regression analysis showed that the immunophenotyping predicted by the optimal model was an independent risk factor of unfavorable DFS (p = 0.009) and OS (p = 0.008) in LSCC patients. Conclusions: Whole tumor-based CT radiomics could serve as a potential predictive biomarker of immunophenotyping and outcome prediction in LSCC patients. [ABSTRACT FROM AUTHOR]

Introduction: Recently, the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system was updated for its 8th edition. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful imaging tool to diagnose and predict prognoses for esophageal cancer. However, there was no previous study to explore the role of FDG PET/CT in the staging system based on the 8th edition. The prognostic value of FDG PET/CT was investigated in patients with esophageal squamous cell carcinoma (SqCC) considering the new 8th AJCC/UICC staging system. Methods: Subjects were 721 patients with esophageal SqCC undergoing pretherapeutic FDG PET/CT. Clinico-pathological variables and the maximum standardized uptake value (SUVmax) of the primary tumor were included in survival analysis. Subgroup analysis was performed to compare hazard ratios according to pathological stage and SUVmax. A new staging classification including FDG uptake was proposed. Results: In multivariate survival analysis, pathological stage and SUVmax of the primary tumor were selected as independent prognostic factors for overall survival in both the 7th and 8th editions. The proposed new staging system showed better discrimination for overall survival between stage I and II than did the conventional staging system (hazard ratios: 2.250 vs. 1.341). Conclusions: The FDG uptake of the primary tumor was found to be an independent prognostic factor along with pathological stage based on both 7th and 8th AJCC/UICC staging systems in patients with esophageal SqCC. The suggested new staging system including SUVmax was better for predicting prognoses than the conventional staging system. [ABSTRACT FROM AUTHOR]

Background: Observational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, and treatment. However, few studies have examined the causal association between them. Methods: Summary data of chemokines and lung cancer were obtained from genome-wide association studies. Mendelian randomization (MR) analyses were performed by five methods, Inverse variance weighted (IVW), Weighted median estimation, MR-Egger, Simple mode and Weighted, with IVW as the primary analysis method. Sensitivity analysis was used to assess the reliability of the MR results. Multivariate Mendelian randomization studies were used to infer whether causality was influenced by potential mediators. The expression levels of CCL21 were analyzed by quantitative real-time PCR. Results: We found that CCL21 was negatively associated with lung adenocarcinoma risk. CCL25 was positively associated with lung squamous cell carcinoma risk. CCL5 was negatively associated with small cell lung cancer risk. CCL21, CCL24, CCL27, and CCL28 was positively associated with small cell lung cancer risk. After multivariate Mendelian randomization adjustment for smoking behavior, it was found that the effect of CCL25 on lung squamous cell cancer disappeared, and the effect of CCL21 on small cell lung cancer was quite opposite to the univariate. The receiver operating characteristic curve indicated that chemokines had high accuracy in the diagnosis of lung cancer. CCL21 expression levels showed large differences in lung adenocarcinoma cells. Conclusion: These results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer. [ABSTRACT FROM AUTHOR]

The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy.A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory.Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%.The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) poses a substantial threat to human health. The development of radioresistance in esophageal cancer cells is a critical factor contributing to local treatment failure and an unfavorable prognosis in affected patients. A comprehensive analysis was performed using bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data from esophageal squamous cell carcinoma (ESCC) samples. Radioresistant ESCC cell lines were generated to explore the functional role of CCNG1. Various techniques, including gene knockdown, flow cytometry, and apoptosis assays, were utilized to evaluate alterations in radiosensitivity, cell cycle progression, and cell survival in response to CCNG1 modulation. Elevated CCNG1 expression was associated with poor clinical outcomes in ESCC patients and contributed to various malignant phenotypes in ESCC cells. In radioresistant ESCC cell lines, CCNG1 knockdown markedly increased radiosensitivity, as demonstrated by enhanced G2/M phase arrest and apoptosis following radiation exposure. CellChat analysis indicated a correlation between CCNG1 and the Wnt/β-catenin signaling pathway, while western blot (WB) analysis confirmed that CCNG1 functions as a downstream effector of Wnt/β-catenin. Our study has identified CCNG1 as a key regulator of radiosensitivity in ESCC, mediated through its interaction with the Wnt/β-catenin signaling pathway. Targeting the Wnt/β-catenin/CCNG1 axis presents a promising therapeutic strategy to enhance the efficacy of radiotherapy in ESCC, potentially overcoming radioresistance and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) serves as a vital component in the chemotherapeutic approach to treat esophageal squamous cell carcinoma (ESCC). However, prolonged CDDP application frequently culminates in resistance, compromising therapeutic outcomes. Through genome-wide CRISPR library screening, our study elucidates the mechanisms underlying this resistance, pinpointing CYFIP2 as a pivotal mediator. Notably, the involvement CYFIP2 is characterized by pronounced autophagic activity and the modulation of multiple cellular pathways. Empirical validation was achieved by treating ESCC cell lines with CDDP, which resulted in an upsurge of CYFIP2 expression. The functional impact of CYFIP2 was further delineated through knockdown experiments, where a marked suppression in cell proliferation was observed, alongside a discernible decline in reactive oxygen species levels. This was complemented by a suite of assays and microscopic techniques, including GFP-LC3, mRFP-GFP-LC3, electron microscopy and western blot, which collectively affirmed the inhibitory effect of CYFIP2 knockdown on autophagic processes, particularly impeding autophagosome formation and their subsequent fusion with lysosomes. In vivo studies have also confirmed that CYFIP2 knockdown limits tumor progression and increases CDDP efficacy. Conclusively, our findings introduce CYFIP2 as a novel contributor to CDDP resistance in ESCC, underscoring its potential as a therapeutic target. This revelation not only deepens our understanding of resistance mechanisms but also paves the way for novel oncotherapeutic strategies, promising enhanced treatment efficacy against ESCC. [ABSTRACT FROM AUTHOR]

Background: Sulfur microbial diet (SMD) is a dietary pattern closely related to the intestinal load of sulfur-metabolizing microbes in humans. Diet and microbes may play an important role in the carcinogenesis of esophagus. However, epidemiological studies on SMD and esophageal cancer (EC) risk are scarce. Here, we evaluated this association based on a large American cohort. Methods: In the cohort of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a SMD score was calculated to evaluate participants' compliance of SMD pattern, with higher scores presenting greater adherence. Cox hazards regression model was used to explore the association between the SMD score and the incidence of EC, esophageal squamous cell carcinoma (ESCC), and esophageal adenocarcinoma (EA). Subgroup analyses were conducted to figure out potential modifiers interacting with SMD on EC. Sensitivity analyses were used to testify the robustness of our main result. Results: Among 101,752 participants, 154 EC cases, consisted of 41 ESCC cases and 97 EA cases, were identified with mean follow-up of 8.9 years. In the fully adjusted model, the highest versus the lowest quartiles of the SMD score were found to be associated with an increased risk of EC and ESCC (EC: HRQ4 vs. Q1: 1.64; 95% CI: 1.05, 2.56; P = 0.016 for trend; ESCC: HRQ4 vs. Q1: 2.37; 95% CI: 1.02, 5.47; P = 0.031 for trend), while not significantly associated with increases risk of EA (HRQ4 vs. Q1: 1.41; P = 0.144 for trend). The main result remained through a series of sensitivity analyses. Subgroup analyses showed a stronger association between SMD and EC in participants with no regular consumption of aspirin (HRQ4 vs. Q1: 1.90; 95% CI: 1.04, 3.47) than in those using aspirin regularly (HRQ4 vs. Q1: 1.37; 95% CI: 0.71, 2.66) (P = 0.008 for interaction). Conclusion: Adherence to the SMD pattern may be associated with increased risks of EC and ESCC, particularly for EC in individuals who do not regularly consume aspirin. [ABSTRACT FROM AUTHOR]

Background: Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods: LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results: A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions: Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe. [ABSTRACT FROM AUTHOR]

To explore diagnostic and prognostic biomarkers in the progression of oral squamous cell carcinoma (OSCC) and to reveal their regulatory mechanisms in key pathways. A RayBiotech protein chip was used to screen differentially expressed serum proteins in OSCC, oral leukoplakia (OLK), and healthy participants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to determine the pathways enriched by characteristic differential proteins. Immunohistochemical analysis and western blotting were used to verify the expression of characteristic differential proteins and key regulatory factors in human tissues and in a nude mouse model. Fibroblast growth factor 6 (FGF6) was identified as a key differential protein and was weakly expressed in OSCC tissues. The mitogen-activated protein kinases (MAPK) and PI3K-AKT pathways were identified as key signaling pathways. The results showed that pERK, Cyclin D1, pAKT, and BCL2 were highly expressed in OSCC, Caspase9 was lowly expressed in OSCC. With an increase in FGF6 expression in nude mice, the expression of FGFR4, pERK, Cyclin D1, pAKT, BCL2, GPX4, and ACSL4 increased, and the expression of Caspase9 decreased. FGF6 may change the expression of apoptosis-related proteins and proliferation factors by binding to FGFR4 in the PI3K-AKT/MAPK pathway and may inhibit the ferroptosis of OSCC, thereby possibly participating in the process of inhibiting OSCC. [ABSTRACT FROM AUTHOR]

Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota‐based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease‐free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP‐plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP‐plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions We aimed to investigate the pattern, risk, and treatment of subsequent events after curative‐intent treatment of lip cancer.This retrospective cohort study included 313 patients treated for lip cancer from 2011 to 2021 in a tertiary oncological center.After a median follow‐up time of 29.16 months, 145 (46.32%) patients presented with second primary tumors, 93% of which were skin carcinomas. Locoregional recurrence occurred in 7.9% of cases, with 2.5% with nodal recurrence. The 1‐, 5‐, and 10‐year cumulative second primary tumor probabilities were 32.8%, 60.92%, and 70.92%, respectively. A higher risk was observed in elderly patients and basal cell carcinoma cases located on the cutaneous surface of the upper lip. Regional metastasis but not second primary tumors negatively impacted survival.Our study helps fill a literature gap, structuring specific recommendations regarding evaluations and follow‐up protocols for patients with lip cancer. Since cutaneous second primary tumors were the most common second event, standard skin examination is key. Age and histology were significant predictors for second primary tumors. For cases of locally advanced lip squamous cell carcinoma, standard guidelines for head and neck cancer must be followed. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusion Histone lysine lactylation (Kla) plays a vital role in cancer progression. However, the prognostic value of histone Kla in oral squamous cell carcinoma (OSCC) remains unclear.OSCC RNA expression data were obtained from the TCGA and GEO databases. We explored the prognostic value of histone Kla in OSCC via constructing a Cox model and determined the role of Kla in OSCC drug susceptibility and tumor microenvironment (TME). In addition, the biological roles of candidate biomarkers were identified.A total of 1223 Kla‐specific genes were obtained, with 228 DEKlaGs in OSCC. GO and KEGG enrichment analyses suggested that DEKlaGs contributed to inflammatory and cancer progression. A Cox model in accordance with BCAM, CGNL1, DGKG, and OLR1 could predict OSCC patient prognosis accurately. Subsequently, Kla‐induced prognostic genes were identified to play a crucial role in OSCC drug therapy and TME. Moreover, BCAM was identified as a biomarker that promoted OSCC invasion, angiogenesis, and chemotherapy resistance.Kla was identified to be associated with OSCC prognosis, drug therapy, and TME. Histone Kla‐induced BCAM was identified to play a crucial role during OSCC progression, suggesting that Kla is promising to be a novel therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

Enhanced infiltration of eosinophils is observed surrounding solid tumors. Some studies indicate that Eosinophil extracellular traps (EETs) play a crucial role in tumor progression and metastasis. However, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study established a gene set associated with eosinophil differentiation, chemotaxis, and EETs release from previous research. Employing bioinformatics techniques, the expression and biological significance of these genes in HNSCC were analyzed. Briefly, unsupervised clustering based on expression patterns of 133 EETs-related genes to classify TCGA-HNSCC patients. Immune cell infiltration patterns were assessed using "ImmuCellAI" package. A prognostic model was constructed using ten algorithms, with EETs-related gene sets as input features. Here, unsupervised clustering of samples into two types revealed worse prognosis for Cluster 1 (C1) patients after the first year. Cluster 2 (C2) exhibited higher ImmuneScore, but with a distinct immune cell infiltration pattern from the C1. Additionally, high eosinophil abundance only in the C2 had a positive prognostic impact. Serine peptidase inhibitor kazal type 5 (SPINK5) emerged as a potential key gene mediating the formation of EETs in HNSCC. EETs not only exhibit a positive correlation with diverse anti-cancer pathways but also demonstrate positive associations with processes such as proliferation, migration, and other critical pathways. The random survival forest (RSF) model was identified as the optimal eosinophil-related prognostic model. Collectively, this study elucidates the potential impact and mediating pathways of EETs on tumors, providing a reference for targeted therapy based on EETs-related genes. [ABSTRACT FROM AUTHOR]

Background: Treatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider. Methods: Newly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017–December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan–Meier analysis. Outcomes were assessed at a minimum of 6 months' follow-up (cutoff: 30 June 2021). Results: Among 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0–1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7–29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5–7.6), 5.2 (95% CI: 4.6–7.6), and 2.3 (95% CI: 2.1–3.0) months, respectively; for the subgroup of patients with ECOG PS 0–1, rwToT was 9.4 (95% CI: 5.0–20.8), 7.1 (95% CI: 5.0–10.1), and 2.9 (95% CI: 2.2–4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9–17.9), 14.8 (95% CI: 10.5–19.4), and 9.1 (95% CI: 7.1–11.5) months; for the subgroup of patients with ECOG PS 0–1, median rwOS was 25.1 [95% CI: 14.9–not reached (NR)], 17.6 (95% CI: 14.3–NR), and 11.3 (95% CI: 9.2–21.3) months, respectively. For ECOG PS 0–1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9–NR) and NR for PDM and PDC, respectively. For ECOG PS 0–1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1–NR) and 11.2 (95% CI: 9.1–21.3) months for PDC and PBC, respectively. Conclusion: Our real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment. [ABSTRACT FROM AUTHOR]

Transoral robotic surgery (TORS) has become a common surgical approach for the treatment of both benign and malignant conditions of the oropharynx. While the newer da Vinci Xi platform has largely replaced the previous Si model in many institutions, the reported outcomes with this system in head and neck surgery are limited. We report the feasibility of using the da Vinci Xi platform for managing oropharyngeal cancer and obstructive sleep apnea in a low-volume center. This retrospective review from a consecutive case series includes demographic, procedural, and outcome data from all patients who underwent TORS using the da Vinci Xi platform at a single institution over a 5-year period from 2019 to 2023. Thirty-five patients (19 males and 16 females) underwent TORS for a variety of indications. No patients were excluded from the study. There were no mortalities, readmissions, or severe complications directly related to the primary surgery. Our case series demonstrates that TORS is feasible with the da Vinci Xi system even in low-volume centers and supports the existing data suggesting that the Xi platform has an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Background: Recent studies have underscored the biological significance of RNA modifications in tumorigenicity and progression. However, the potential roles of RNA modifications in immune regulation and the formation of the tumor microenvironment (TME) in head and neck squamous carcinoma (HNSC) remain unclear. Methods: We collected 199 untreated HNSC samples and clinicopathological data from Fujian Provincial Cancer Hospital. MeRIP-seq and RNA-seq were performed to generate methylation and gene expression profiles, respectively. Consensus molecular subtyping was employed to identify prognosis-related genes and RNA modification patterns in HNSC. Experiments confirmed the potential oncogenic behavior influenced by key genes. Molecular subtypes were identified through consensus clustering and validated using external cohort validation sets. Results: Among the RNA modification-related genes, IGF2BP1 emerged as the most prognostic. HNSC patients were categorized into high and low IGF2BP1 expression groups. High-expressing patients exhibited poorer survival and reduced chemosensitivity, coupled with increased tumor mutational burden, low PD-L1 expression, and limited immune cell infiltration, indicative of aggressive disease. Analysis revealed two distinct RNA modification patterns associated with IGF2BP1 expression: biosynthetically intense type (BIT) and oncogenically active type (OAT), each characterized by distinct clinical features, outcomes, and biological pathways. In an independent immunotherapy cohort, BIT patients displayed enhanced immune responses and sustained clinical benefits. Conclusions: This study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Adjuvant radiotherapy to the vulva in vulvar squamous cell carcinoma (VSCC) is frequently performed albeit strong evidence is lacking. This systematic review aims to summarize the current literature on this topic. 19 retrospective studies were included and analyzed, focusing on the primary outcome of local recurrence. The publications present conflicting results. While the benefit of adjuvant radiotherapy to the groins in case of node-positive VSCC is well established, the indication criteria and effectiveness of adjuvant radiotherapy to the vulva remain unclear. Based on the studies included in this review, the current evidence suggests that adjuvant radiotherapy to the vulva might not significantly reduce the risk of recurrence or only in certain subgroups. Most of the studies do not consider individual risk factors such as HPV status, resection margin, lymph node stage, grading and others. As a result, the comparability and reliability of these findings are limited. This review aims to highlight the need of further research addressing the risk stratification, considering both oncologic risk factors and adverse events. • Indication criteria are controversial as potential prognostic factors are not consistently considered across studies. • Lymph node status is the most important prognostic factor and should trigger discussion about adjuvant local treatment. • Future studies should aim to differentiate subgroups and stratify patients according to risk factors such as HPV. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative‐intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma.A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine‐learning k‐means algorithm were used to determine threshold values.A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n = 207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n = 62; 16.1%). The majority of patients had ≥9 metastatic foci (n = 174; 45.3%), followed by one focus (n = 74; 19.3%) and two foci (n = 32; 8.3%). Cox regression and machine‐learning k‐means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p < .001), by identifying a threshold of two locations.Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two. [ABSTRACT FROM AUTHOR]

Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome‐related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome‐related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC50 of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome‐related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High‐risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti‐PD‐L1 and anti‐CTLA‐4 immunotherapy, whereas low‐risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis‐related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome‐related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Background: Esophageal Squamous Cell Carcinoma (ESCC) poses a significant health challenge in China due to its high incidence and mortality. Single-cell transcriptomics has transformed the approach to cancer research, allowing detailed analysis of cellular and molecular heterogeneity. The interaction between the transcription factor STAT1 and the tumor suppressor LHPP is crucial, potentially influencing cancer progression and therapeutic outcomes. Objective: This study aims to explore the molecular mechanisms and cellular dynamics underlying ESCC, with a focus on the role of transcription factors, particularly STAT1, and its regulatory relationship with LHPP, in the pathogenesis of ESCC. Methods: Utilizing single-cell transcriptomics data sourced from the public database GEO (GSE160269), we identified major cell types and their transcriptomic changes in ESCC patients. Differential gene expression profiles were examined to understand the dynamics of the tumor microenvironment (TME). A cohort of 21 ESCC patients was recruited to validate the findings. Furthermore, in ESCC cell lines, we validated the transcriptional regulatory relationship between STAT1 and LHPP. Results: Our analysis identified six major cell types within the ESCC microenvironment, revealing significant changes in cellular composition and gene expression profiles associated with tumorigenesis. Notably, a novel association between STAT1's regulatory role over LHPP was observed, suggesting a complex regulatory loop in ESCC pathogenesis. Elevated STAT1 and reduced LHPP expression were confirmed in patient samples with STAT1 negatively regulates LHPP expression at the promoter level; when the promoter binding motif regions were mutated, the transcriptional repression ability on LHPP was weakened. Conclusion: The study highlights STAT1 as a core regulator in ESCC, directly influencing LHPP expression. The findings offer novel insights into the molecular mechanisms driving ESCC, shedding light on the cellular alterations and gene regulation dynamics within the ESCC microenvironment. This research provides a foundation for developing targeted therapeutic strategies, potentially utilizing the STAT1-LHPP axis as a focal point in ESCC treatment and prognosis. [ABSTRACT FROM AUTHOR]

Background: Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex and heterogeneous diseases driven by uncontrolled cell growth and proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them a promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value in HNSCC through comprehensive bioinformatics analysis, with a particular focus on the therapeutic potential of placental growth factor (PIGF). Methods: Transcriptome data for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed genes (DEGs) were identified and analyzed for their prognostic significance. Exercise-related gene sets were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, were conducted. The biological functions and clinical implications of key genes were further explored through single-gene expression analysis, immune infiltration analysis, and in vitro cellular experiments. Results: The study identified exercise-related genes associated with survival prognosis in HNSCC. GO and KEGG pathway analyses highlighted the biological functions of these genes, and Kaplan-Meier survival curves confirmed their prognostic value. PIGF expression analysis using TCGA data showed its diagnostic potential, with higher expression linked to advanced tumor stages. Single-cell sequencing revealed PIGF's role in the tumor microenvironment. In vitro experiments demonstrated that PIGF plays a pivotal role in enhancing cell proliferation and colony formation in HNSCC, with PIGF knockdown significantly impairing these functions, highlighting its importance in tumor growth regulation. Additionally, PIGF's predictive performance in drug sensitivity across cancer datasets suggests its potential as a pharmacological target, offering opportunities to modulate the immune microenvironment and improve therapeutic outcomes in cancer treatment. Conclusion: This study provides new insights into the molecular mechanisms underlying HNSCC and identifies exercise-related genes, particularly PIGF, as promising biomarkers for clinical treatment and personalized medicine. By focusing on PTMs and their role in cancer progression, our findings suggest that targeting PIGF may offer innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BCa) is one of the most common urological cancers and remains a leading cause of cancer-related mortality worldwide. Bladder cancer is associated with a range of risk factors, with smoking being one of the most significant contributors. In addition to smoking, exposure to certain chemicals, particularly aromatic amines found in industries such as dye, rubber, leather, and textiles, also increases the risk of bladder cancer. In low-and-middle countries with lower Human Development Index (HDI), data on the underlying causes, incident rate, modes of presentation, treatment, and prognosis of bladder cancer remains unclear and often appear to be inadequate. This study aimed to assess the prevalence, mode of presentation, treatment, and risk factors associated with bladder cancer in Johannesburg, South Africa. By examining these factors, the study seeks to identify possible patterns or predisposing factors that contribute to the development and progression of bladder cancer, which could generate insights that could help to reduce the significant morbidity and mortality associated with this cancer. Methods: This retrospective study analyzed secondary data from 115 patients who were treated in the radiation oncology unit of an academic hospital between January 2010 and December 2020. By reviewing the medical records of these patients, the study aimed to gather comprehensive information on the prevalence of bladder cancer, modes of presentation, treatment approaches, and associated risk factors. Bladder cancer in this study was assessed using a comprehensive analysis of patient data on demographics, risk factors, clinicopathological aspects, and the specific therapies received. A comparison of patients with squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder was conducted as part of this study. This comparison aimed to explore differences in demographic profiles, risk factors, clinicopathological characteristics, and treatment outcomes between these two histological subtypes. Results: A total of 115 patients presenting with bladder cancer symptoms were referred to the academic hospital for evaluation and treatment. The incidence rate of bladder cancer was highest among patients with a mean age of 60.7 ± 14.9. Males constituted 60.9% of the cases, resulting in a male-to-female ratio of 1.6:1. The most common risk factors associated with bladder cancer complications included smoking, being male, black ethnicity and increasing age. Transitional cell carcinoma remained the most prevalent histological subtype at the academic hospital, compared to squamous cell carcinoma (SCC). Patients with transitional cell carcinoma (TCC) were more likely to be older (odds ratio (OR): 1.03, 95% Confidence Interval (CI): 1.01–1.06, p = 0.029), male (OR: 2.60, 95% CI:1.10–6.04, p = 0.030). The study also found that most of the TCC cases were among black patients, though white patients were four times more likely to present with TCC compared to SCC (OR:4.22, 95% CI: 1.43–12.48, p = 0.009). Conclusion: Bladder cancer is still widespread in LMICs, with lower HDI, with elderly males being at risk. To aggressively prevent mortality and morbidity from bladder cancer, bladder cancer health awareness must be maintained to improving prevention, as well as early detection, management and comprehensive patient care and health services for bladder cancer patients. These findings highlight the importance of targeted screening and prevention strategies for high-risk groups, particularly older males with a history of smoking. [ABSTRACT FROM AUTHOR]

Introduction: Human oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown. Methods: Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-β were detected using ELISA assay. Results: We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-β. Discussion: Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-β. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC [ABSTRACT FROM AUTHOR]

Objectives: The main objective of this study was to evaluate the alignment between treatment decisions made during multidisciplinary team meetings (MTMs) and the treatments received by patients with upper aerodigestive tract cancers. The secondary objective was to identify factors influencing potential discrepancies. Methods: This retrospective, single-center study was conducted at a tertiary referral center and included 147 patients diagnosed with squamous cell carcinoma of the upper aerodigestive tract. Patients were divided into two groups based on the match between MTM-decided and actual treatments. Multivariate analysis was performed to assess factors independently associated with discrepancies. Results: Out of 147 patients, 28 (19%) received treatment that did not align with MTM decisions. Among these, eight died before treatment, one patient refused care, five received supportive care, five patients underwent surgery, three received radiotherapy alone, one patient underwent surgery and adjuvant radiochemotherapy, one patient underwent surgery and adjuvant radiotherapy alone, three patients received radiochemotherapy, and one patient received palliative chemotherapy. Independent significant factors associated with non-concordance included poor performance status (PS) and treatment not received at a tertiary reference center. Treatment shifts mainly involved downgrading from curative to palliative care. Conclusions: This study highlights the importance of patient health status in determining deviations from MTM decisions. Further efforts should focus on improving the integration of patient comorbidities and health status into MTM decision-making to optimize care delivery. [ABSTRACT FROM AUTHOR]

Objectives: This study used multilevel social determinants of health (SDoH) models to determine how SDoH influence different sexes of patients diagnosed with HPV-positive oropharyngeal squamous cell cancers (OPSCC) across the US. Methods: This was a retrospective cohort study assessing HPV-confirmed patients with oropharyngeal squamous cell cancers from 2010 to 2018 using census-level Yost Index socioeconomic status (SES) score and rurality–urbanicity measures alongside individual-level race–ethnicity while stratifying by biological sex. Age-adjusted multivariate regressions were performed for survival, treatment receipt, and delay of treatment initiation (of 3+ months). Results: Across 14,076 OPSCC-HPV-positive patients, delay of treatment uniquely featured positive predictors for males of black race–ethnicity (OR, 2.07; 95% CI, 1.68–2.54) and poor Yost SES (1.43; 1.24–1.65). Five-year all-cause mortality uniquely showed positive predictors of females of black race–ethnicity (2.74; 1.84–4.71) and of males with poor Yost SES (1.98; 1.79–2.19). Three-year all-cause mortality shared positive predictors across sexes but were exacerbated in females of black race–ethnicity (2.50; 1.82–3.44) compared to males (2.23; 1.91–2.60); this was reversed for poor Yost SES (male, 1.92, 1.76–2.10; female, 1.60, 1.32–1.95). Surgery showed negative predictors of black race–ethnicity that displayed worsened effects in females (0.60, 0.44–0.79) versus males (0.75, 0.66–0.86). First-line radiation receipt uniquely featured negative predictors for males of black race–ethnicity (0.73; 0.62–0.86) with poor Yost SES (0.74; 0.68–0.82). Conclusions: Comprehensive models of multilevel SDoH displayed exacerbated disparity effects of community-level SES in males and black race–ethnicity among female HPV-positive OPSCC patients. These objective comparisons of specific SDoH factors inform providers and policy direction on how to strategically target the most pertinent SDoH factors affecting a rapidly growing cancer population. [ABSTRACT FROM AUTHOR]

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan–Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43–0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29–0.93]), but not in stage IVB patients (HR: 0.76 [0.51–1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35–0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status. [ABSTRACT FROM AUTHOR]

Molecular testing is recommended in patients with metastatic non-small cell lung cancer (NSCLC), but the extent of its use in Poland is unknown. The aim of the POL-MOL study was to investigate the frequency of using molecular testing in Polish patients with NSCLC. The invited Polish oncologists completed two questionnaires, and data for 1001 patients undergoing systemic treatment for NSCLC were collected. The use of molecular tests for the following genetic mutations was recorded: EGFR (del19, sub21), EGFR (other than del19/sub21), EGFR T790M, ALK (expression and rearrangement), RET, NTRK, ROS1, BRAF, HER2, and MET, as well as for immunochemical assessment of programmed cell death ligand 1 (PD-L1). Thanks to the weighting procedure, the results are representative of the population of Polish patients treated for NSCLC. Molecular tests were applied in 78% of patients with NSCL, 70% of patients with NSCLC not otherwise specified, and in 12% of patients with squamous cell carcinoma of the lung. The frequency of application increased with disease stage in all groups. In patients with squamous cell carcinoma, approximately 30% of tests for EGFR, ALK, and RET mutations were positive, which confirms the importance of testing at least a preselected subgroup of patients. [ABSTRACT FROM AUTHOR]

Background: Malignant epithelial nail unit tumors pose significant diagnostic and therapeutic challenges due to their clinical presentation often mimicking benign conditions and due to the need to preserve as much nail unit function as possible during surgery. Early detection is crucial, even if none of these tumors represent a life-threatening disease. Objectives: This review focus on squamous cell carcinoma, verrucous carcinoma, eccrine porocarcinoma, onychocytic carcinoma, basal cell carcinoma, malignant onychopapilloma, malignant onycholemmal cyst and onycholemmal carcinoma. Methods: Existing literature on the aforementioned tumors has been revised and synthesized. Results: Clinical presentation, pathology, diagnostic procedures, risk factors and the challenges associated with surgical management have been described in detail. Conclusions: Malignant epithelial tumors of the nail unit require careful evaluation and management due to their complex presentation. Early detection and an informed surgical approach are essential to improve patient outcomes and minimize complications. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) has established predictive biomarkers that enable decisions on treatment regimens for many patients. However, resistance to therapy is widespread. It is therefore essential to have a panel of molecular biomarkers that may help overcome therapy resistance and prevent adverse effects of treatment. We performed in silico analysis of NSCLC prognostic indicators, separately for adenocarcinomas and squamous carcinomas, by using The Cancer Genome Atlas (TCGA) and non-TCGA data sources in cBioPortal as well as UALCAN. This review describes lung cancer biology, elaborating on the key genetic alterations and specific genes responsible for resistance to conventional treatments. Importantly, we examined the mechanisms associated with resistance to immune checkpoint inhibitors. Our analysis indicated that a robust prognostic biomarker was lacking for NSCLC, especially for squamous cell carcinomas. In this work, our screening uncovered previously unidentified prognostic gene expression indicators, namely, MYO1E, FAM83 homologs, and DKK1 for adenocarcinoma, and FGA and TRIB1 for squamous cell carcinoma. It was further observed that overexpression of these genes was associated with poor prognosis. Additionally, FAM83 homolog and TRIB1 unexpectedly harbored copy number amplifications. In conclusion, this study elucidated novel prognostic indicators for NSCLC that may serve as targets to overcome therapy resistance toward improved patient outcomes. [ABSTRACT FROM AUTHOR]

The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor–stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC. After a literature screening, 24 studies dealing with the TSR and survival outcomes were included. The TSR showed a significant association with overall survival (OS) in both unadjusted and adjusted measures (RR 2.04, CI 1.57–2.65, p < 0.01; HR 2.36 CI 1.89–2.94, p < 0.00001), with an even stronger prognostic potential in oral cavity/oral tongue cancers (RR 2.44 CI 1.84–3.22, p < 0.00001). The TSR also showed prognostic value when dealing with cancer-specific survival and was associated with a reduction in disease-free survival (DFS). In particular, the TSR also retained its prognostic role in terms of DFS when specifically considering early-stage cancers in both unadjusted and adjusted analyses (RR 1.81 CI 1.57–2.10, p < 0.00001; HR 2.09 CI 1.58–2.76, p < 0.00001). Therefore, we conclude that the TSR is a reliable prognostic marker that is easy to assess in routine histological slides and can be effectively implemented in the routine evaluation of HNSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients. This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with the head and neck region being the most common location. Perineural invasion (PNI), or the invasion of cancer into and around nerves, is a high-risk factor in cSCC associated with poor outcomes. The mechanisms of PNI in cSCC are poorly understood, but recent studies suggest that cross-communication between nerve components and cancer is a contributing factor. A better understanding of the mechanisms that promote PNI may lead to new therapies that improve outcomes in cSCC patients. Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the role of three specific proteins—FGF8, ALK, and EML4—in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a common type of esophageal cancer. The aim of the study was to assess whether the presence and levels of these proteins could indicate which patients are at a higher risk of poor survival following surgery. By analyzing tissue samples from 122 patients, who underwent surgical removal of their cancer, the study discovered that an increase in FGF8 protein levels is associated with a reduced chance of survival. Additionally, the study found a significant correlation between FGF8 and alterations in the ALK and EML4 proteins. These results suggest that FGF8 could serve as a valuable marker for predicting patient outcomes and might also become a target for future therapies aimed at improving survival rates in ESCC patients. FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients' overall survival (OS) (p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK (p = 0.04) and EML4 (p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer represents a main public health issue around the world due to the mortality rates associated with it, the lack of effective and potent drugs, the multitude of side effects and the expensive treatments. Until now, no natural alternative therapeutic methods have been found beneficial enough to replace conventional drugs. Thus, bioactive compounds with anticancer properties can represent a necessary alternative through a targeted molecular approach to the multiple pathways involved in carcinogenesis. This review explores how the therapeutic potential of natural compounds can be harnessed and how they can be used as adjuvant therapies for oral cancer treatment. The collected results focused only on plant extracts and biologically active metabolites known for their antioxidant, anti-inflammatory and antitumor potential, which can be described as future chemopreventive agents against oral cancer, alone or in therapeutic combinations. Background: With a significant increase in both incidence and mortality, oral cancer—particularly oral squamous cell carcinoma (OSCC)—is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. Methods: This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Results: Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. Conclusions: This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with skin lesions suspicious for skin cancer or atypical melanocytic nevi of uncertain malignant potential often present to dermatologists, who may have variable dermoscopy triage clinical experience. We evaluated the clinical utility of a digital dermoscopy image-based artificial intelligence algorithm (DDI-AI device) on the diagnosis and management of skin cancers. Thirty-six United States board-certified dermatologists evaluated 50 cases with clinical images and DDI of the same skin lesions (25 malignant and 25 benign), first without and then with knowledge of the DDI-AI device output. We identified that when using the DDI-AI device, management sensitivity, management specificity, diagnostic sensitivity, and diagnostic specificity all increased over baseline use of clinical images and dermoscopy images. Hence, the use of the DDI-AI device may quickly, safely, and effectively improve dermoscopy performance, skin cancer diagnosis, and management when used by dermatologists, independent of training and experience. Background: Patients with skin lesions suspicious for skin cancer or atypical melanocytic nevi of uncertain malignant potential often present to dermatologists, who may have variable dermoscopy triage clinical experience. Objective: To evaluate the clinical utility of a digital dermoscopy image-based artificial intelligence algorithm (DDI-AI device) on the diagnosis and management of skin cancers by dermatologists. Methods: Thirty-six United States board-certified dermatologists evaluated 50 clinical images and 50 digital dermoscopy images of the same skin lesions (25 malignant and 25 benign), first without and then with knowledge of the DDI-AI device output. Participants indicated whether they thought the lesion was likely benign (unremarkable) or malignant (suspicious). Results: The management sensitivity of dermatologists using the DDI-AI device was 91.1%, compared to 84.3% with DDI, and 70.0% with clinical images. The management specificity was 71.0%, compared to 68.4% and 64.9%, respectively. The diagnostic sensitivity of dermatologists using the DDI-AI device was 86.1%, compared to 78.8% with DDI, and 63.4% with clinical images. Diagnostic specificity using the DDI-AI device increased to 80.7%, compared to 75.9% and 73.6%, respectively. Conclusion: The use of the DDI-AI device may quickly, safely, and effectively improve dermoscopy performance, skin cancer diagnosis, and management when used by dermatologists, independent of training and experience. [ABSTRACT FROM AUTHOR]