Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Analysis of Saliva as a Diagnostic Specimen for Rapid Classification of Oral Squamous Cell Carcinoma Using Chemometrics Methods.

BACKGROUND & AIM: Recent advancements in analytical techniques have highlighted the potential of Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy as a quick, cost-effective, non-invasive, and efficient tool for cancer diagnosis. This study aims to evaluate the effectiveness of ATR-FTIR spectroscopy in combination with supervised machine learning classification models for diagnosing OSCC using saliva samples. METHODS & MATERIALS: Eighty unstimulated whole saliva samples from OSCC patients and healthy controls were collected. The ATR-FTIR spectroscopy was performed and spectral data were used to classify healthy and OSCC groups. The data were analyzed using machine learning classification methods such as Partial Least Squares-Discriminant Analysis (PLS-DA) and Support Vector Machine Classification (SVM-C). The classification performance of the models was evaluated by computing sensitivity, specificity, precision, and accuracy. RESULTS: The samples were classified into two classes based on their spectral data. The obtained results demonstrate a high level of accuracy in the prediction sets of the PLS-DA and SVM-C models, with accuracy values of 0.960 and 0.962, respectively. The OSCC group sensitivity values for both PLS-DA and SVM-C models was 1.00, respectively. CONCLUSION: The study indicates that ATR-FTIR spectroscopy, combined with chemometrics, is a potential method for the non-invasive diagnosis of OSCC using saliva samples. This method achieved high accuracy and the findings of this study suggest that ATR-FTIR spectroscopy could be further developed for clinical applications in OSCC diagnosis.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.

Unraveling the key role of chromatin structure in cancer development through epigenetic landscape characterization of oral cancer.

Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Risk of lymph node metastasis in T1 tonsil squamous cell carcinomas patients according to age stratification at diagnosis.

BACKGROUND: The objective of this study is to assess the association between age and lymph nodes metastasis (LNM) in T1 tonsil squamous cell carcinomas (TSCC) patients. METHODS: Patients with T1 TSCC were extracted from the SEER database between 2005 and 2014. Univariate and multivariate logistic regression models were produced to recognize the association between age and risk factors of LNM. RESULTS: A total of 2430 patients were analyzed. Younger patients more frequently presented with LNM compared to their older peers (P < 0.01, respectively.). In multivariate analyses, older age was associated with a significantly lower risk of LNM. Compared to patients aged 29-39-years-old, the hazard ratios for patients aged 40-49, 50-59, 60-69, and 70-88 years old were 0.911 (95 % confidence interval [CI] 0.370-2.245), 0.641 (95 % CI 0.268-1.535), 0.511 (95 % CI 0.212-1.231), and 0.236 (95 % CI 0.095-0.584), respectively. Subgroups analysis shows that the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients (P < 0.05, respectively). CONCLUSION: Our study demonstrates that younger patients with T1 TSCC had a higher risk of LNM than their old peers and the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients. More accurate assessments of LNM and prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck will be imperative for reducing recurrence in younger T1 TSCC.

Lymph Node Evolution in Eyelid and Orbit Squamous Cell Carcinomas.

OBJECTIVES: To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node involvement among tumor characteristics. METHODS: All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses. RESULTS: Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution. CONCLUSION: Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Long-Term Follow-Up of Computer-Assisted Microvascular Mandibular Reconstruction: A Retrospective Study.

Background: Virtual surgical planning has become a well-established practice in head and neck surgery. In oncological surgery, it permits the achievement of safe margins resections and ensures functional reconstructions and optimal esthetic outcomes. This study aimed to evaluate the long-term outcomes after virtually planned mandibular microvascular reconstruction, focusing on functional and esthetic results, as well as health-related quality of life. Methods: A long-term retrospective evaluation of 17 patients with oral cavity malignancy who underwent computer-assisted mandibular resection and reconstruction was performed. Functional and esthetic outcomes were analyzed using the EORTC, QLQ-C30, H&N35, and FACE-Q questionnaires. Results: Time since reconstruction ranged from 7 to 14 years. Patients reported high functional levels on the QLQ-C30 functional scales but lower scores on H&N35. On FACE-Q, patients demonstrated higher appraisal and satisfaction with their smiles compared to their overall facial appearance. Conclusions: In this retrospective case series, patients undergoing computer-assisted mandibular reconstruction for oral malignancies achieved good long-term functional and esthetic outcomes. Although limited by the small sample size, these results support the enduring benefits of virtual planning for mandibular reconstruction. To minimize declines in function and appearance, considerations should include immediate dental implants, enhanced reconstruction of the temporomandibular joint, newer methods of radiotherapy to minimize xerostomia, and oral exercises to prevent trismus.

Establishment of a prognostic model for hypoxia-associated genes in OPSCC and revelation of intercellular crosstalk.

Hypoxia exerts a profound influence on the tumor microenvironment and immune response, shaping treatment outcomes and prognosis. Utilizing consistency clustering, we discerned two hypoxia subtypes in OPSCC bulk sequencing data from GEO. Key modules within OPSCC were identified through weighted gene correlation network analysis (WGCNA). Core modules underwent CIBERSORT immune infiltration analysis and GSEA functional enrichment. Univariate Cox and LASSO analyses were employed to construct prognostic models for seven hypoxia-related genes. Further investigation into clinical characteristics, the immune microenvironment, and TIDE algorithm prediction for immunotherapy response was conducted in high- and low-risk groups. scRNA-seq data were visually represented through TSNE clustering, employing the scissors algorithm to map hypoxia phenotypes. Interactions among cellular subpopulations were explored using the Cellchat package, with additional assessments of metabolic and transcriptional activities. Integration with clinical data unveiled a prevalence of HPV-positive patients in the low hypoxia and low-risk groups. Immunohistochemical validation demonstrated low TDO2 expression in HPV-positive (P16-positive) patients. Our prediction suggested that HPV16 E7 promotes HIF-1α inhibition, leading to reduced glycolytic activity, ultimately contributing to better prognosis and treatment sensitivity. The scissors algorithm effectively segregated epithelial cells and fibroblasts into distinct clusters based on hypoxia characteristics. Cellular communication analysis illuminated significant crosstalk among hypoxia-associated epithelial, fibroblast, and endothelial cells, potentially fostering tumor proliferation and metastasis.

Clinically relevant immune subtypes based on alternative splicing landscape of immune-related genes for lung cancer advanced PPPM approach.

Background: Alternative splicing (AS) occurs in the process of gene post-transcriptional process, which is very important for the correct synthesis and function of protein. The change of AS pattern may lead to the change of expression level or function of lung cancer-related genes, and then affect the occurrence and development of lung cancers. The specific AS pattern might be used as a biomarker for early warning and prognostic assessment of a cancer in the framework of predictive, preventive, and personalized medicine (PPPM; 3PM). AS events of immune-related genes (IRGs) were closely associated with tumor progression and immunotherapy. We hypothesize that IRG-AS events are significantly different in lung adenocarcinomas (LUADs) vs. controls or in lung squamous cell carcinomas (LUSCs) vs. controls. IRG-AS alteration profiling was identified to construct IRG-differentially expressed AS (IRG-DEAS) signature models. Study on the selective AS events of specific IRGs in lung cancer patients might be of great significance for further exploring the pathogenesis of lung cancer, realizing early detection and effective monitoring of lung cancer, finding new therapeutic targets, overcoming drug resistance, and developing more effective therapeutic strategies, and better used for the prediction, diagnosis, prevention, and personalized medicine of lung cancer. Methods: The transcriptomic, clinical, and AS data of LUADs and LUSCs were downloaded from TCGA and its SpliceSeq databases. IRG-DEAS events were identified in LUAD and LUSC, followed by their functional characteristics, and overall survival (OS) analyses. OS-related IRG-DEAS prognostic models were constructed for LUAD and LUSC with Lasso regression, which were used to classify LUADs and LUSCs into low- and high-risk score groups. Furthermore, the immune cell distribution, immune-related scores, drug sensitivity, mutation status, and GSEA/GSVA status were analyzed between low- and high-risk score groups. Also, low- and high-immunity clusters and AS factor (SF)-OS-related-AS co-expression network and verification of cell function of CELF6 were analyzed in LUAD and LUSC. Results: Comprehensive analysis of transcriptomic, clinical, and AS data of LUADs and LUSCs identified IRG-AS events in LUAD (n = 1607) and LUSC (n = 1656), including OS-related IRG-AS events in LUAD (n = 127) and LUSC (n = 105). A total of 66 IRG-DEAS events in LUAD and 89 IRG-DEAS events in LUSC were identified compared to controls. The overlapping analysis between IRG-DEASs and OS-related IRG-AS events revealed 14 OS-related IRG-DEAS events for LUAD and 16 OS-related IRG-DEAS events for LUSC, which were used to identify and optimize a 12-OS-related-IRG-DEAS signature prognostic model for LUAD and an 11-OS-related-IRG-DEAS signature prognostic model for LUSC. These two prognostic models effectively divided LUAD or LUSC samples into low- and high-risk score groups that were closely associated with OS, clinical characteristics, and tumor immune microenvironment, with significant gene sets and pathways enriched in the two groups. Moreover, weighted gene co-expression network (WGCNA) and nonnegative matrix factorization method (NMF) analyses identified four OS-relevant subtypes of LUAD and six OS-relevant subtypes of LUSC, and ssGSEA identified five immunity-relevant subtypes of LUAD and five immunity-relevant subtypes of LUSC. Interestingly, splicing factors-OS-related-AS network revealed hub molecule CELF6 was significantly related to the malignant phenotype in lung cancer cells. Conclusions: This study established two reliable IRG-DEAS signature prognostic models and constructed interesting splicing factor-splicing event networks in LUAD and LUSC, which can be used to construct clinically relevant immune subtypes, patient stratification, prognostic prediction, and personalized medical services in the PPPM practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00366-4.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

Variation of resection margins in oral cancer in dependence of tumor stage and subsite - a retrospective cohort study.

OBJECTIVES: Surgical resection is a key component of the treatment of head and neck cancer and the achievement of free surgical margins are essential for the patients' outcome in terms of survival. While there is a general recommendation for a free resection range of 5 mm, up to date, there is a lack of investigations on the quality of tumor resection in dependence of affected subsite and tumor stage. In the presented study, predictors for the achieved resection margins in surgically treated oral squamous cell carcinomas were analyzed. MATERIALS AND METHODS: A cohort of 567 patients was included in a retrospective analysis and resection status with exact margin ranges were analysed. Tumor stage, affected subsite and the results of the intraoperative frozen section analysis were assessed. Primary endpoint was the achieved resection margin in mm, secondary endpoints were overall and progression-free survival. RESULTS: The observed mean values of minimal resection margins differed significantly between the investigated subsites (p = 0.042),pathological tumor stages (p < 0.001) and in tumors which demonstrated perineural infiltration (Pn1, p = 0.002). Furthermore, there was a significant impact of the results of the intraoperative frozen section analysis on progression-free and overall survival (p < 0.001). CONCLUSIONS: Our data clearly indicate that resection status differs between tumors of different subsites and tumor stages. CLINICAL RELEVANCE: Clinical procedures should be adapted in order to achieve similar certainty in all resections, and, thus to improve patients' outcome.

Delay in Cutaneous Squamous Cell Carcinoma Diagnosis Due to Interrupted Services Is Associated with Worse Prognoses and Modified Surgical Approaches.

BACKGROUND: The delayed diagnosis of skin tumors is associated with a worsened prognosis. The impact of the interruption of clinical and surgical health services during the COVID-19 pandemic lockdowns has been documented among many pathologies. The impact of delayed diagnoses on patients with cutaneous squamous cell carcinomas (cSCCs) is poorly defined. OBJECTIVE: To compare patient and lesion characteristics and the surgical management of excised cSCCs prior to the pandemic shutdown of services (2018-2019) with the phase following the pandemic's second wave (2021-2022). METHODS: An observational, single-center, cross-sectional study of 416 surgically excised cSCCs over the course of two years was performed. Only patients with histologically confirmed cSCC were enrolled. Data collection included patient demographics and lesion characteristics, time to surgery, surgical approach, and histological data. RESULTS: More cSCC lesions were excised prior to the interruption of services (n = 312 vs. n = 186). Lesions were significantly larger (1.7 ± 1.2 vs. 2.1 ± 1.5 cm; p = 0.006) and more invasive (52% vs. 89%; p < 0.001), in the period 2021-2022. Surgical reconstructive techniques were significantly different (p = 0.001). Metastatic involvement was confirmed in three subjects (one in 2018-2019 and two in 2021-2022). There were no significant differences in the time to surgery or patient characteristics. Multivariable regression analysis identified a 4.7-times higher risk of tumor invasion (OR 4.69, 95%CI 2.55-8.16, p < 0.001), a two-times higher chance of dermo-epidermal grafts (OR 2.06, 95%CI 1.09-3.88, p = 0.025), and a 3.2-times higher risk of positive surgical margins (OR 3.21, 95%CI 1.44-7.17, p = 0.004). CONCLUSIONS: Diagnostic delays of cutaneous SCCs associated with reduced patient access to clinical and diagnostic services are associated with a 4.7-times increased risk of more severe invasion, a three-times increased risk of positive surgical margins, and a significant impact on surgical management, compared to the pre-pandemic period. Comparable patient cohort characteristics and time to surgery remained unchanged.

Cascade Nanoreactor Employs Mitochondrial-Directed Chemodynamic and δ-ALA-Mediated Photodynamic Synergy for Deep-Seated Oral Cancer Therapy.

The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. A cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment is introduced. Utilizing iron oxide and mesoporous silica, the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA), is developed. Triphenylphosphine (TPP) modification facilitates mitochondrial targeting, while tumor cell membrane (TCM) coating provides homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM demonstrate efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggers δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria undergoes Fenton chemistry for CDT. The synergistic interaction of PDT and CDT increases cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic mechanisms, ultimately leading to tumor cell death. PDT/CDT-induced apoptosis generates δ-ALA-containing apoptotic bodies, enhancing antitumor efficacy in deep tumor cells. The anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment.

Alteration of SERPINH1 is associated with elevated expression in head and neck squamous cell carcinomas and its clinicopathological significance.

BACKGROUND/PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer-related death worldwide and contributes significantly to the burden of disease in South Asia, partially due to the lack of effective screening strategies. Identifying essential biomarkers is crucial for improved prognosis and treatment. This study investigates the potential of SERPINH1 as a prognostic marker in HNSCC, highlighting its significance amidst the molecular complexity. METHODS: The Cancer Genome Atlas HNSCC cohort, comprised of 520 tumors and 44 normal tissues, was analyzed using cBioportal, UALCAN, and Protein atlas tools. Expression patterns, survival outcomes, and clinical correlations of SERPINH1 were evaluated. In-depth analyses involved oral squamous cell carcinoma (OSCC) patient samples, protein expression, and functional exploration using various in-silico tools. RESULTS: SERPINH1 exhibited significant alteration and upregulation in HNSCC and OSCC, indicating its pan-cancer potential. Immunohistochemistry confirmed its overexpression in primary HNSCC tumors. Association analyses linked altered SERPINH1 levels with tumor stage, grade, metastasis, human papillomavirus (HPV) status, and patient prognosis. Functional analyses unveiled SERPINH1's involvement in critical cellular pathways and interactions with various proteins. CONCLUSION: The significant alteration of SERPINH1 associated with upregulated expression in HNSCC and OSCC positions it as a promising diagnostic and prognostic marker. Further investigations are warranted to elucidate the underlying molecular mechanisms, paving the way for targeted therapeutic interventions and continued exploration of various malignancies.

Squamous cell carcinoma of the temporal bone: the impact of local control on survival.

BACKGROUND: Squamous cell carcinoma (SCC) of the temporal bone (TB) is a rare pathology originating from the external auditory canal (EAC). Surgery remains the gold standard to achieve local control.Aims/Objectives:The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) after surgery of the SCC of EAC. MATERIAL AND METHODS: A retrospective chart review in a tertiary referral center included 26 patients: 23 were operated with lateral temporal bone resection (LTBR, n = 10) and extended temporal bone resection (ETBR, n = 13). The outcomes were OS and DFS. RESULTS: Adjuvant radiotherapy was performed in 91.3% (n = 21/23). Mean age was 60.8 and sex ratio was 1. Median follow-up was 43 months; The 5-years OS was 90% (± 9.5%) and 47.7% (± 12.9%) for stage I/II and III/IV respectively (p = .033). DFS was 67.6% (IC 95%, 51.4%-88.9%) without statistical difference between early advanced stage. Incomplete margins (p = .004) and Stage IV(p < .001) were associated with poorer DFS. Free margins significantly correlated with better OS (HR = 9.8, p = .04). CONCLUSION: En bloc surgical resection with free margins, coupled with postoperative radiotherapy, provides optimal local control. For stage IV tumors, where complete margins are achievable, ETBR is recommended to enhance local control.

[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

A dataset of optical spectra and clinical features acquired on human healthy skin and on skin carcinomas.

Optical spectroscopy is studied to contribute to skin cancer diagnosis. Indeed, optical spectra are modified along cancer progression and provide complementary information (e.g., on metabolism and tissue structure) to clinical examination for surgical guidance [1,2]. The current original dataset is made of autofluorescence and diffuse reflectance spectra acquired in vivo on 131 patients' skin with the SpectroLive device [3,4]. Spatially-resolved spectroscopy measurements were performed using a multi-fiber optic probe featuring 4 distances (0.4-1 mm) between excitation and collection optical fibers: spatial resolution allows spectra acquired at different distances to carry information from different depths in skin tissues. Five types of autofluorescence spectra were acquired using five different wavelength excitations (on the 365-415 nm spectral range) in order to collect information on several skin endogenous fluorophores (e.g., flavins, collagen). A sixth light source (white broadband) was used to acquire diffuse reflectance spectra carrying information about skin scattering properties and skin endogenous absorbers such as melanin and hemoglobin. Patients were proposed to be included into the clinical trial if they were suspected of suffering from actinic keratoses (precancerous skin lesions) or from basal or squamous cell carcinomas: in all cases, complete diagnostics is provided in the dataset. To increase the interest of the dataset and evaluate the dependence of optical spectra (intensity, shape) not only on pathological states but also on healthy skin features (civil age, skin age, gender, phototype, anatomical site), spectra were acquired for all 131 patients on two so-called "reference" skin sites known to rarely suffer from skin cancer: palm of the hand (featuring a thick skin type) and inner wrist (featuring thin skin). Spectra are available in .tab files: first column displays the spectral range on which intensity spectra were recorded (317-788 nm) and each following column provides an intensity spectrum acquired by each spectrometer for a given combination of light source excitation and distance. Each of the 131 folders corresponding to each of the 131 patients contains a .json file providing patients clinical features: gender, civil age, skin age, phototype score and class. All .tab files names include anatomical site and anatomopathological diagnostics of the skin site on which spectra were acquired: codes were defined to match a letter or an acronym to each diagnostic and anatomical site. To ensure quality control, a spectrum was acquired on the same calibration standard before starting spectra acquisition on each patient. It is therefore possible to follow the impact of the acquisition optical chain ageing during the 4.5 years that the patients were included. This dataset can be used by epidemiologists for the characterization of populations affected by skin cancers (gender ratio, mean age, anatomical sites typically affected, etc.); it may also be used by researchers in artificial intelligence to develop innovative methods to process such data and contribute to non-invasive diagnostics of skin cancers whose incidence is steadily increasing.