Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging.

Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

Definitive chemoradiotherapy for a patient with anal cancer after renal transplantation.

Patients after renal transplantation are susceptible to secondary malignancies, including anal squamous cell carcinoma. Chemoradiotherapy is the standard treatment for anal squamous cell carcinoma; however, typical irradiation fields for anal cancer encompass a transplanted kidney located in the right iliac fossa, which causes complete renal dysfunction. Thus, typical irradiation fields are not feasible for this population. Additionally, standard concurrent chemotherapy demonstrates nephrotoxicity. Here, we report a case of modified definitive chemoradiotherapy for a 40-year-old patient with locally advanced perianal squamous cell carcinoma after renal transplantation whose abdominoperineal resection was difficult because of a history of repeated open surgeries and long-term steroids. We modified the cranial side of the elective nodal irradiation fields in this case to spare the transplanted kidney, considering the lymph chains of the perianal tumor. We then used continuous 5-fluorouracil to avoid nephrotoxicity of mitomycin C, considering his life expectancy. Modified definitive chemoradiotherapy achieved complete remission with expected toxicities. Now, approximately five years after the procedure, the patient remains disease-free, preserving anal and renal function. Definitive chemoradiotherapy using modified irradiation fields and chemotherapy may be an option for patients with anal squamous cell carcinoma after renal transplantation.

Effects of Chemotherapy and Radiation Therapy on Early Laryngeal Cancers.

Background/Aim: Treatments for early laryngeal squamous cell carcinoma (SCC) include radiotherapy (RT), chemoradiotherapy (CRT), and larynx-preserving surgery. In this study, early laryngeal SCC was treated with RT in patients with stage I (T1N0) tumors and with CRT and docetaxel (DOC) in patients with stage II (T2N0) tumors and the treatment results and effectiveness of the chemotherapy were compared. Patients and Methods: A total of 78 patients with early-stage laryngeal SCC were enrolled in this study. The T1N0 patients received radiation for the primary lesions as outpatients at a total dose of 63-70 Gy. By contrast, the T2N0 patients were hospitalized and treated with CRT, receiving a total radiation dose of 66-70 Gy. Docetaxel (DOC, 10 mg/m2) was administered intravenously once a week for 6-8 consecutive weeks concurrently with radiotherapy. The adverse events and survival rates with local control rates were examined. Results: The number of non-glottic T2N0 patients was significantly higher than that of T1N0 patients. Although all patients completed their treatment schedule, significantly more grade 3 adverse events were observed in the T2N0 patients, in particular mucositis and dermatitis, than in T1N0 patients. The 5-year overall survival rate, disease specific survival rate, local control rate, and laryngeal preserve rate of the T1N0 and T2N0 patients were 86.1, 93.3, 88.6, and 94.3% and 85.9, 88.0, 93.1, and 93.1%, respectively. Conclusion: CRT with docetaxel showed the best therapeutic outcomes for the treatment of laryngeal SCC in patients with T2N0 tumours, with a higher local control rate, effective laryngeal preservation, and relatively few adverse events.

Laryngeal Preservation Rate and Salvage Therapy Following Initial Recurrence in a Real-world Setting After Definitive Radiation Therapy in Patients With Locally Advanced Laryngeal Squamous Cell Carcinoma.

Background/Aim: The larynx plays a pivotal role in vocalization and airway protection, and laryngeal cancer manifests through various symptoms. Contemporary strategies focus on laryngeal preservation, particularly through non-surgical modality therapies that utilize radiotherapy. The aim of this study was to assess the laryngeal preservation rate after definitive radiation therapy in patients with locally advanced laryngeal squamous cell carcinoma and investigate salvage therapy subsequent to the initial recurrence in a real-world context. Patients and Methods: Analysis included a total of 40 patients with locally advanced laryngeal squamous cell carcinoma who were treated with definitive radiotherapy in the University of Tokyo Hospital. Treatment involved external beam radiotherapy (70 Gy in 35 fractions) with elective nodal irradiation. The main study outcomes were assessment of survival, overall survival, local control, and the factors influencing laryngeal preservation. Results: The patients exhibited a median age of 64.5 years, and 80% of them were men. Chemotherapy was administered to 82.5% of the patients. The 3-year overall survival, progression-free, and laryngeal preservation survival rates were 86.3%, 66.8%, and 78.4%, respectively. Univariate and multivariate analyses identified chemotherapy to be significantly associated with favorable laryngeal preservation survival (p<0.001). Conclusion: Definitive radiotherapy results in favorable outcomes for laryngeal preservation in locally advanced laryngeal squamous cell carcinoma. This study emphasizes the importance of chemotherapy in comprehensive patient management. Nevertheless, larger prospective studies are crucial to validate and optimize therapeutic approaches for this condition.

Mutant Nrf2E79Q enhances the promotion and progression of a subset of oncogenic Ras keratinocytes and skin tumors.

Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2E79Q expression, one of the most common activating mutations in human SCCs, on tumor promotion and progression in the mouse skin multistage carcinogenesis model using a DMBA-initiation/TPA-promotion protocol where the Hras A->T mutation (Q61L) is the canonical driver mutation. Nrf2E79Q expression was temporally and conditionally activated in the epidermis at two stages of tumor development: 1) after DMBA initiation in the epidermis but before cutaneous tumor development and 2) in pre-existing DMBA-initiated/TPA-promoted squamous papillomas. Expression of Nrf2E79Q in the epidermis after DMBA initiation but before tumor occurrence inhibited the development/promotion of 70% of squamous papillomas. However, the remaining papillomas often displayed non-canonical Hras and Kras mutations and enhanced progression to SCCs compared to control mice expressing wildtype Nrf2. Nrf2E79Q expression in pre-existing tumors caused rapid regression of 60% of papillomas. The remaining papillomas displayed the expected canonical Hras A->T mutation (Q61L) and enhanced progression to SCCs. These results demonstrate that mutant Nrf2E79Q enhances the promotion and progression of a subset of skin tumors and alters the frequency and diversity of oncogenic Ras mutations when expressed early after initiation.

Can Hounsfield unit density value accurately predict prelaryngeal invasion in laryngeal carcinoma cases.

OBJECTIVE: The Hounsfield unit density value (HUDV) is a relative quantitative measurement of radio density used by radiologists in the interpretation of computed tomography (CT) images. Our aim is to investigate the role of HUDV in evaluating pre-epiglottic space (PES) involvement of laryngeal carcinoma. METHODS: Seventy-four patients treated for laryngeal carcinoma in our clinic between 2014 and 2019 were included in the study. The invasion status of PES was determined radiologically and pathologically. HUDV was measured with a circular selected region of interest, with a constant size of 10 mm2 for PES. The relationship between patological PES invasion, radiological PES invasion, and HUDV was evaluated. RESULTS: Measuring HUDV to determine PES invasion (74.3 %) was significantly higher than​​ conventional CT evaluation (59.5 %) (p = 0.001). The agreement coefficient (kappa value) of the conventional CT evaluation and the HUDV regarding PES involvement was 0.673, which was interpreted as 'good'. CONCLUSION: HUDV could be used as an additional tool in diagnosing pre-epiglottic space invasion in laryngeal cancer.

Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites?

A subset of head and neck squamous cell carcinomas present solely as metastatic disease in the neck and are of unknown primary origin (SCCUP). Most primary tumors will ultimately be identified, usually in the oropharynx. In a minority of cases, the primary site remains elusive. Here, we examine the role of ancillary testing, including mutational signature analysis (MSA), to help identify likely primary sites in such cases. Twenty-two cases of SCCUP in the neck, collected over a 10-year period, were classified by morphology and viral status; including human papillomavirus (HPV) testing by p16 immunohistochemistry (IHC) and RT-qPCR, as well as Epstein-Barr virus (EBV) testing by EBER-ISH. CD5 and c-KIT (CD117) IHC was done to evaluate for possible thymic origin in all virus-negative cases. Whole exome sequencing, followed by MSA, was used to identify UV signature mutations indicative of cutaneous origin. HPV was identified in 12 of 22 tumors (54.5%), favoring an oropharyngeal origin, and closely associated with nonkeratinizing tumor morphology (Fisher's exact test; p = 0.0002). One tumor with indeterminant morphology had discordant HPV and p16 status (p16+/HPV-). All tumors were EBV-negative. Diffuse expression of CD5 and c-KIT was identified in 1 of 10 virus-negative SCCUPs (10%), suggesting a possible ectopic thymic origin rather than a metastasis. A UV mutational signature, indicating cutaneous origin, was identified in 1 of 10 (10%) virus-negative SCCUPs. A cutaneous auricular primary emerged 3 months after treatment in this patient. Primary tumors became clinically apparent in 2 others (1 hypopharynx, 1 hypopharynx/larynx). Thus, after follow-up, 6 tumors remained unclassifiable as to the possible site of origin (27%). Most SCCUPs of the neck in our series were HPV-associated and thus likely of oropharyngeal origin. UV signature mutation analysis and additional IHC for CD5 and c-KIT for possible thymic origin may aid in further classifying virus-negative unknown primaries. Close clinical inspection of hypopharyngeal mucosa may also be helpful, as a subset of primary tumors later emerged at this site.

Jejunum free flap for head and neck reconstruction, a step-by-step surgical technique videos.

Circular pharyngolaryngectomy for oncologic resection requires a tubular reconstruction. Different options can be proposed to the patient: digestive free flap, fasciocutaneous flap, or musculocutaneous flap. The jejunum free flap is a tubular flap commonly used in esophageal and pharyngeal reconstruction with good functional outcomes and an acceptable rate of complications. Reconstruction with a jejunum free flap is an ideal choice. Patients at Gustave Roussy Institute (Villejuif, France) were offered a jejunum flap free flap for all circular pharyngolaryngectomies. The surgical technique is explained with a step-by-step video. The jejunum flap free flap has many advantages in circular pharyngolaryngectomy. This video article explains surgical steps for other teams.

JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

Integrating lipid metabolite analysis with MRI-based transformer and radiomics for early and late stage prediction of oral squamous cell carcinoma.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) presents significant diagnostic challenges in its early and late stages. This study aims to utilize preoperative MRI and biochemical indicators of OSCC patients to predict the stage of tumors. METHODS: This study involved 198 patients from two medical centers. A detailed analysis of contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) MRI were conducted, integrating these with biochemical indicators for a comprehensive evaluation. Initially, 42 clinical biochemical indicators were selected for consideration. Through univariate analysis and multivariate analysis, only those indicators with p-values less than 0.05 were retained for model development. To extract imaging features, machine learning algorithms in conjunction with Vision Transformer (ViT) techniques were utilized. These features were integrated with biochemical indicators for predictive modeling. The performance of model was evaluated using the Receiver Operating Characteristic (ROC) curve. RESULTS: After rigorously screening biochemical indicators, four key markers were selected for the model: cholesterol, triglyceride, very low-density lipoprotein cholesterol and chloride. The model, developed using radiomics and deep learning for feature extraction from ceT1W and T2W images, showed a lower Area Under the Curve (AUC) of 0.85 in the validation cohort when using these imaging modalities alone. However, integrating these biochemical indicators improved the model's performance, increasing the validation cohort AUC to 0.87. CONCLUSION: In this study, the performance of the model significantly improved following multimodal fusion, outperforming the single-modality approach. CLINICAL RELEVANCE STATEMENT: This integration of radiomics, ViT models, and lipid metabolite analysis, presents a promising non-invasive technique for predicting the staging of OSCC.

Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

The two-faced role of RNA methyltransferase METTL3 on cellular response to cisplatin in head and neck squamous cell carcinoma in vitro model.

Background: RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of N 6-methyladenosine (m6A) modification. This epigenetic feature contributes to the structural and functional regulation of RNA and consequently may promote tumorigenesis, tumor progression, and cellular response to anticancer treatment (chemo-, radio-, and immunotherapy). In head and neck squamous cell carcinoma (HNSCC), the commonly used chemotherapy is cisplatin. Unfortunately, cisplatin resistance is still a major cause of tumor relapse and patients' death. Thus, this study aimed to investigate the role of METTL3 on cellular response to cisplatin in HNSCC in vitro models. Materials and methods: HNSCC cell lines (H103, FaDu, and Detroit-562) with stable METTL3 knockdown (sgMETTL3) established with CRISPR-Cas9 system were treated with 0.5 tolerable plasma level (TPL) and 1 TPL of cisplatin. Further, cell cycle distribution, apoptosis, CD44/CD133 surface marker expression, and cell's ability to colony formation were analyzed in comparison to controls (cells transduced with control sgRNA). Results: The analyses of cell cycle distribution and apoptosis indicated a significantly higher percentage of cells with METTL3 knockdown 1) arrested in the G2/S phase and 2) characterized as a late apoptotic or death in comparison to control. The colony formation assay showed intensified inhibition of a single cell's ability to grow into a colony in FaDu and Detroit-562 METTL3-deficient cells, while a higher colony number was observed in H103 METTL3 knockdown cells after cisplatin treatment. Also, METTL3 deficiency significantly increased cancer stem cell markers' surface expression in all studied cell lines. Conclusion: Our findings highlight the significant influence of METTL3 on the cellular response to cisplatin, suggesting its potential as a promising therapeutic target for addressing cisplatin resistance in certain cases of HNSCC.

Heterogeneity of cancer-associated fibroblasts and tumor-promoting roles in head and neck squamous cell carcinoma.

Tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) has a major influence on disease progression and therapy response. One of the predominant stromal cell types in the TME of HNSCC is cancer-associated fibroblasts (CAF). CAF constitute a diverse cell population and we are only at the beginning of characterizing and understanding the functions of various CAF subsets. CAF have been shown to interact with tumor cells and other components of the TME to shape mainly a favourable microenvironment for HNSCC progression, although some studies report existence of tumor-restraining CAF subtypes. The numerous pathways used by CAF to promote tumorigenesis may represent potential therapeutic targets. This review summarizes current knowledge on the origins, subtypes and mechanisms employed by CAF in HNSCC. The aim is to contribute to the understanding on how CAF actively influence the TME and modulate different immune cell types, as well as cancer cells, to establish a conducive setting for cancer growth. Although CAF are currently a promising therapeutic target for the treatment of other types of cancer, there is no significant therapeutic advancement in HNSCC.

Clinical Outcome in Patients with Large Sinonasal Tumors with Intracranial Extension.

Objectives Malignant tumors of the sinonasal cavities with extension to the frontal skull base are rare and challenging pathologies. Combined-approach surgery using a frontobasal craniotomy and endoscopic sinus surgery with reconstruction of the anterior skull base followed by adjuvant radiotherapy is a preferred treatment strategy in selected cases. Morbidity and mortality rates are high in this population. We aim to add our experience to the current literature. Design We performed a retrospective cross-sectional single center study of the long-term clinical outcome in a tertiary university referral hospital in the Netherlands between 2010 and 2021. Descriptive statistics and frequency distributions were performed Participants Patient, tumor, treatment, complications and survival characteristics of eighteen consecutive patients were extracted from the electronic health records. Main Outcome Measures The primary outcome measures are progression free survival, overall survival and complication rate. Results Eighteen consecutive patients were included with a mean age of 61 (SD ± 10) years (range 38-80); ten males and eight females. Gross total resection was achieved in 14 (77%) patients. Eleven (61%) patients underwent local radiotherapy, one (5%) chemotherapy and three (17%) a combination of both. Mean follow-up duration was 49 months (range 3 - 138). Three (17%) patients died in hospital due to post-operative complications. Six (33%) patients died during follow-up due to disease progression. Mean progression-free survival was 47 months (range 0 - 113). Conclusion In conclusion, the overall survival was 50% for this group of patients with large sinonasal tumors. Progressive disease affects survival rate severely. Surgical complications were seen in five (28%) patients. Radiotherapy is associated with high complication rates. Radiation necrosis was a serious complication in two patients and could be treated with high dose steroids.

Treatment outcomes of elective neck dissection in intrathoracic esophageal carcinoma.

In the present study, the outcomes of elective neck dissection in patients with intrathoracic esophageal squamous cell carcinoma were investigated. From January 2016 to December 2022, 21 patients who underwent esophagectomy and elective neck dissection (both neck level IV) for intrathoracic esophageal squamous cell carcinoma were enrolled. Of these 21 patients, 19 patients were male and 2 were female. A total of 11 patients received concurrent chemoradiotherapy (CCRT) as preoperative treatment. As a result of elective neck dissection at both neck level IV, occult neck metastasis of esophageal squamous cell carcinoma was diagnosed in 3 cases, all of which involved left neck lymph nodes. The incidence of occult neck metastasis was statistically significant in patients with preoperative CCRT, high T stage and high N stage (P<0.05). In addition, 16 out of 21 patients had been under follow-up without disease recurrence after the completion of treatment. However, 3 out of 21 patients succumbed to esophageal squamous cell carcinoma and 2 out of 21 patients were alive with stable disease of esophageal carcinoma. The follow-up period was 19.2±18.4 months. In conclusion, three-field lymph node dissection for intrathoracic esophageal squamous cell carcinoma may be necessary in patients with certain phenotypes, such that collaboration between thoracic surgeons and otolaryngologists may help reduce surgical complications.

The Epidemiology and Survival Outcomes of Adult Conjunctival Malignancies in Germany: A Decade-Long Population-Based Analysis (2009-2019).

PURPOSE: This study aims to evaluate the epidemiological patterns, treatment strategies, and survival outcomes of conjunctival malignancies in Germany between 2009 and 2019. METHODS: A total of 1,532 cases were analyzed, with the crude incidence rate calculated. The survival rates were investigated using life tables and Cox regression analysis. RESULTS: The overall incidence rate was 1.7 per million. Incidence rates varied across age groups, peaking in the 75+ age group. Carcinomas (43%), melanomas (30%), and lymphomas (20%), were the most prevalent malignancies. Of the total cases with reported treatment, surgical intervention was undertaken in 64.5% of the patients. The 5-year overall survival rates were 90.4% for lymphomas, 73.8% for melanomas, and 72.9% for carcinomas. Age at diagnosis emerged as a significant prognostic factor in the Cox regression analysis. CONCLUSIONS: This study provides the first population-based incidence data on conjunctival malignancies in Germany, noting a generally low incidence with survival rates comparable to other regions. The findings underscore the importance of consistent reporting and further research into risk factors for a deeper understanding of these malignancies. The study calls for improved reporting systems and further investigations into genetic factors and targeted prevention strategies for high-risk groups.

Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. METHODS: A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. RESULTS: The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. CONCLUSIONS: Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model.

OBJECTIVE: Combing PD-1/PD-L1 immune checkpoint inhibitors with natural products has exhibited better efficacy than monotherapy. Hence, the purpose of this research was to examine the anti-cancer effects of brusatol, a natural quassinoid-terpenoid derived from Brucea javanica, when used in conjunction with an anti-mouse-PD-1 antibody in a murine head and neck squamous cell carcinoma (HNSCC) model and elucidate underlying mechanisms. DESIGN: A murine HNSCC model and an SCC-15 cell xenograft nude mouse model were established to investigate the anti-cancer effects of brusatol and anti-PD-1 antibody. Mechanistic studies were performed using immunohistochemistry. Cell proliferation, migration, colony formation, and invasion were evaluated by MTT, migration, colony formation, and transwell invasion assays. PD-L1 levels in oral squamous cell carcinoma (OSCC) cells were assessed through qRT-PCR, flow cytometry, and western blotting assays. The impact of brusatol on Jurkat T cell function was assessed by an OSCC/Jurkat co-culture assay. RESULTS: Brusatol improved tumor suppression by anti-PD-1 antibody in HNSCC mouse models. Mechanistic studies revealed brusatol inhibited tumor cell growth and angiogenesis, induced apoptosis, increased T lymphocyte infiltration, and reduced PD-L1 expression in tumors. Furthermore, in vitro assays confirmed brusatol inhibited PD-L1 expression in OSCC cells and suppressed cell migration, colony formation, and invasion. Co-culture assays indicated that brusatol's PD-L1 inhibition enhanced Jurkat T cell-mediated OSCC cell death and reversed the inhibitory effect induced by OSCC cells. CONCLUSIONS: Brusatol improves anti-PD-1 antibody efficacy by targeting PD-L1, suggesting its potential as an adjuvant in anti-PD-1 immunotherapy.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.