Laryngeal carcinoma

喉癌
  • 文章类型: Journal Article
    评估初次治疗的喉鳞状细胞癌(LSCC)患者的初始诊断时表观扩散系数(ADC)对未来转移发展的预测能力。
    经病理证实为非转移性患者的磁共振图像,对未经治疗的LSCC进行回顾性评估.评估了后续的正电子发射断层扫描扫描对转移瘤的扫描。
    共纳入37例患者(男性32例,女性5例),平均年龄62.8±8.9岁。平均肿瘤体积和ADC分别为4.8±62cm3和0.72±0.51×10-3mm2/s,分别。在平均17.5±10.2个月的随访期内,发现了6个局部转移和8个远处转移。发现ADC与远处转移(p=0.046)和局部转移(p=0.042)之间存在显着关联。未来转移性和非转移性初始肿瘤之间的平均ADC值差异显著(p=0.017)。
    治疗前ADC值和初始肿瘤的体积可能提供有关本系列LSCC患者未来转移发展的早期信息。
    UNASSIGNED: To evaluate the predictive capability of the apparent diffusion coefficient (ADC) at initial diagnosis in treatment-naive patients with laryngeal squamous cell carcinoma (LSCC) for the development of future metastases.
    UNASSIGNED: Magnetic resonance images of patients with pathologically proven non-metastatic, treatmentnaive LSCC were retrospectively evaluated. Follow-up positron emission tomography scans were assessed for the scanning of metastases.
    UNASSIGNED: A total of 37 patients (32 males and 5 females) with a mean age of 62.8 ± 8.9 years were enrolled. Mean tumour volume and ADC were 4.8 ± 62 cm3 and 0.72 ± 0.51 × 10-3 mm2/s, respectively. Six local and 8 distant metastases were detected in a mean follow-up period of 17.5 ± 10.2 months. A significant association between ADC and the presence distant metastases (p = 0.046) and local metastases (p = 0.042) was found. The difference in mean ADC values between future metastatic and non-metastatic initial tumours was significant (p = 0.017).
    UNASSIGNED: Pre-treatment ADC values and volume of the initial tumour might provide early information about the development of future metastases in patients with LSCC in this series.
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  • 文章类型: Journal Article
    目的:目的是检测NKG2A及其配体HLA-E的表达水平特征,免疫检查站的新成员,晚期喉癌及其临床病理意义。
    方法:我们利用肿瘤免疫评估资源(TIMER)数据库以及石蜡包埋组织样本的免疫组织化学和qRT-PCR分析,分析了多种类型肿瘤中HLA-E和NKG2A的表达水平。揭示晚期喉癌中临床病理因素与这两种蛋白表达的相关性及其预后意义。
    结果:KLRC1(NKG2A的编码基因)和HLA-E在各种人类癌症中的表达明显高于正常组织。HNSCC也包括在内。KLRC1在不同HPV患者亚组中差异表达,在HPV阳性组中有较高的表达。与此一致,免疫组织化学结果也显示这两种蛋白在肿瘤组织中的高表达。此外,免疫组织化学染色还显示了对NKG2A阳性细胞在肿瘤组织中分布的偏好。临床病理分析还显示,HPV阳性组浸润喉癌组织的NKG2A阳性细胞密度大于HPV阴性组。预后分析表明,该免疫检查点的表达不影响患者的总体生存时间。但HLA-E高表达与患者局部复发显著相关.
    结论:研究结果表明,晚期喉癌中HLA-E和NKG2A的表达水平上调。浸润肿瘤的NKG2A阳性细胞主要分布在癌巢,而浸润细胞数量可能受HPV调控。高表达的HLA-E可能促进晚期喉癌患者的局部复发。
    OBJECTIVE: The purpose was to detected features of the expression levels of NKG2A and its ligand HLA-E, a new member of the immune checkpoints, in advanced laryngeal carcinoma and their clinicopathologic significance.
    METHODS: We analyzed the expression levels of HLA-E and NKG2A in multiple types of tumors utilizing the Tumor Immune Estimation Resource (TIMER) database and immunohistochemistry and qRT-PCR analysis of paraffin embedded tissue samples to reveal the correlations of the clinicopathological factors with the expression of these two proteins in advanced laryngeal carcinoma as well as their prognostic significance.
    RESULTS: KLRC1 (the coding gene of NKG2A) and HLA-E are substantially overexpressed in various human cancers than normal tissues. HNSCC is also included. KLRC1 is differentially expressed in different HPV subgroups of patients, with higher expression in the HPV-positive group. Consistent with this, immunohistochemical results also revealed the high expression of these two proteins in tumor tissue. In addition, immunohistochemical staining also displayed a preference for the distribution of NKG2A-positive cells in tumor tissue. Clinicopathological analyses also displayed that the density of NKG2A-positive cells of the HPV-positive group infiltrating laryngeal carcinoma tissue was larger than that in the HPV-negative group. Prognostic analyses indicated that the expression of this immune checkpoint does not affect the overall survival length of patients, but the highly expressed HLA-E is significantly correlated with local recurrence in the patients.
    CONCLUSIONS: The findings suggest that the expression levels of HLA-E and NKG2A is upregulated in advanced laryngeal carcinoma. The NKG2A-positive cells infiltrating the tumor are mainly distributed in the cancer nest, while infiltrating cell number may be regulated by HPV. The highly expressed HLA-E may promote local recurrence in patients with advanced laryngeal carcinoma.
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  • 文章类型: Case Reports
    咽部皮肤瘘(PCF)是咽部和皮肤之间的异常连接,可在喉切除术后发生。它会对患者的康复产生重大的负面影响,延迟伤口愈合,需要长时间的无口服(NPO)状态,降低生活质量。传统上,PCF的治疗依赖于保守措施或手术干预.然而,负压伤口治疗(NPWT)提供了一种有希望的替代方法。该病例研究涉及三名接受喉切除术并发生术后PCF的患者。所有患者均接受改良的抽吸导管和低负压(20-40mmHg)的NPWT。有了NPWT,所有患者均实现伤口完全闭合,愈合时间从两周到六周不等。这表明与传统方法相比,NPWT可以显着加速PCF的愈合。然而,在颈部区域保持气密敷料可能是具有挑战性的。这项研究强调了NPWT在喉切除术后更快地闭合PCF的潜力。需要进一步的研究来优化NPWT应用技术,探索对长期结果的影响,并建立更广泛的临床使用指南。
    Pharyngocutaneous fistula (PCF) is an abnormal connection between the pharynx and skin that can occur after laryngectomy surgery. It can have a significant negative impact on patient recovery, delaying wound healing, requiring prolonged nil-per-oral (NPO) status, and reducing quality of life. Traditionally, the management of PCF has relied on conservative measures or surgical intervention. However, negative pressure wound therapy (NPWT) offers a promising alternative approach. This case study involves three patients who underwent laryngectomy and developed postoperative PCF. All patients received NPWT with a modified suction catheter and low negative pressure (20-40 mmHg). With NPWT, all patients achieved complete wound closure, with healing times ranging from two weeks to six weeks. This suggests that NPWT may significantly accelerate PCF healing compared to traditional methods. However, maintaining an airtight dressing on the neck region can be challenging. This study highlights the potential of NPWT for faster PCF closure after laryngectomy. Further research is needed to optimize NPWT application techniques, explore the impact on long-term outcomes, and establish guidelines for broader clinical use.
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  • 文章类型: Journal Article
    目的:喉癌和下咽癌(LC/HPC)约占头颈部癌的24%,导致全球每年超过9万人死亡。扩散加权成像(DWI)目前在肿瘤成像中被广泛研究,可以帮助区分细胞肿瘤与其他组织。我们的目标是回顾DWI在三个方面的有效性:诊断,预测预后,并预测LC/HPC患者的治疗反应。
    方法:在PubMed中进行了系统搜索,WebofScience,和Embase。通过计算标准化平均差(SMD)和95%置信区间(CI)对诊断研究进行荟萃分析。
    结果:共纳入16项研究。所有诊断研究(n=9)都能够区分LC/HPC和其他良性喉/下咽病变。这些研究发现LC/HPC具有比非癌性病变更低的表观扩散系数(ADC)值。我们对7项诊断研究的荟萃分析,提供恶性和非恶性组织的ADC值,与非恶性病变相比,LC/HPC的ADC值显着降低(SMD=-1.71,95CI:[-2.00,-1.42],ADC截止值=1.2×103mm2/s)。此外,在预测预后的研究中,67%(4/6)基于治疗前ADC值准确预测结果。同样,在预测治疗反应的研究中,50%(2/4)基于预处理ADC值成功预测结果。总的来说,观察LC/HPC预后或治疗反应的研究发现,喉/下咽治疗前ADC值与良好结局之间存在正相关.
    结论:DWI对LC/HPC诊断有显著帮助。然而,需要进一步的研究来确定DWI在预测LC/HPC患者预后和治疗反应方面的可靠性.
    OBJECTIVE: Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC.
    METHODS: A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies.
    RESULTS: A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 103 mm2/s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes.
    CONCLUSIONS: DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI\'s reliability in predicting prognosis and treatment response in patients with LC/HPC.
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  • 文章类型: Journal Article
    目的:本研究旨在进一步评估泛免疫-炎症值(PIV)作为喉部和咽部肿瘤患者预后标志物的潜在价值。
    方法:选择在山东大学齐鲁医院接受手术治疗的喉咽部肿瘤患者545例。我们确定了PIV的最佳截止值,并将患者分为两组。通过卡方检验和Mann-WhitneyU检验探讨PIV与临床病理特征之间的关系。采用生存分析和Cox回归分析评价PIV与总生存期(OS)和无病生存期(DFS)的关系。我们还比较了PIV与其他炎症相关标志物的预后预测价值。最后,我们基于几个独立的预后参数建立了一个简单的评分预测模型.
    结果:我们发现PIV与临床病理特征如肿瘤分期有统计学关联(p<0.001),节点阶段(p=0.001),术后化疗(p=0.026),血管血栓形成(p=0.027)。生存分析显示PIV升高与OS和DFS降低之间存在显著相关性(p<0.0001)。多因素Cox回归分析进一步证实PIV是预后指标(HR2.507;95%CI1.343-4.681;p=0.004),优于SII,NLR,MLR和PLR。通过多变量Cox回归分析筛选出的独立预后因素中的三个被选择用于创建一致指数为0.756的评分系统。
    结论:喉部和咽部肿瘤患者PIV升高与预后不良相关,提示PIV可能是评估患者预后的重要辅助指标。
    注册号:KYLL-202307-001,日期:2023年7月。
    OBJECTIVE: This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors.
    METHODS: A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters.
    RESULTS: We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756.
    CONCLUSIONS: Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis.
    UNASSIGNED: Registration number: KYLL-202307-001, date: July 2023.
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  • 文章类型: Journal Article
    淋巴结状态对于指导喉癌和下咽癌(LHC)患者的手术方法至关重要。尽管如此,隐匿性淋巴结转移对评估和治疗计划提出了挑战。本研究旨在开发和验证用于评估LHC患者颈淋巴结状态的诊断模型。
    本研究回顾性分析了在耳鼻咽喉头颈外科治疗的285名LHC患者,大坪医院,陆军医科大学,2015年1月至2020年12月。采用单变量和多变量逻辑回归分析构建预测模型。使用辨别和校准来评估模型的预测性能。进行决策曲线分析(DCA)以评价该模型的临床实用性,并使用10倍交叉验证进行验证,保留一次交叉验证,和引导方法。
    这项研究确定了LHC淋巴结转移的重要预测因素。开发了诊断预测模型,并使用列线图进行了可视化。该模型表现出出色的鉴别力,C指数为0.887(95%CI:0.835-0.933)。DCA分析表明了它的实际适用性,多种验证方法证实了其拟合和泛化能力。
    这项研究成功建立并验证了LHC中颈淋巴结转移的诊断预测模型。可视化的列线图为个性化预测患者颈淋巴结状态提供了方便的工具,特别是在隐匿性颈淋巴结转移的情况下,为临床治疗决策提供有价值的指导。
    UNASSIGNED: The lymph node status is crucial for guiding the surgical approach for patients with laryngeal and hypopharyngeal carcinoma (LHC). Nonetheless, occult lymph node metastasis presents challenges to assessment and treatment planning. This study seeks to develop and validate a diagnostic model for evaluating cervical lymph node status in LHC patients.
    UNASSIGNED: This study retrospectively analyzed a total of 285 LHC patients who were treated at the Department of Otolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University, from January 2015 to December 2020. Univariate and multivariate logistic regression analyses were employed to construct the predictive model. Discrimination and calibration were used to assess the predictive performance of the model. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the model, and validation was conducted using 10-fold cross-validation, Leave-One-Out Cross Validation, and bootstrap methods.
    UNASSIGNED: This study identified significant predictors of lymph node metastasis in LHC. A diagnostic predictive model was developed and visualized using a nomogram. The model demonstrated excellent discrimination, with a C-index of 0.887 (95% CI: 0.835-0.933). DCA analysis indicated its practical applicability, and multiple validation methods confirmed its fitting and generalization ability.
    UNASSIGNED: This study successfully established and validated a diagnostic predictive model for cervical lymph node metastasis in LHC. The visualized nomogram provides a convenient tool for personalized prediction of cervical lymph node status in patients, particularly in the context of occult cervical lymph node metastasis, offering valuable guidance for clinical treatment decisions.
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  • 文章类型: Journal Article
    目的:本研究评估了两种高级大型语言模型(LLM)的功效,OpenAI的ChatGPT4和Google的双子座高级,为头颈部肿瘤病例提供治疗建议。目的是评估其在支持多学科肿瘤评估和决策过程中的效用。
    方法:此比较分析检查了ChatGPT4和Gemini对5例假设的头颈部癌的反应,每个代表不同的解剖亚位点。根据最新的国家综合癌症网络(NCCN)指南,通过两个盲板使用总分歧评分(TDS)和人工智能性能仪器(AIPI)对响应进行了评估。使用Wilcoxon符号秩检验和Friedman检验进行统计评估。
    结果:在遵守指南和综合治疗计划方面,两个LLM都提出了ChatGPT4的相关治疗建议,通常优于GeminiAdvanced。ChatGPT4与Gemini高级(中位数2[2-3])相比,AIPI得分更高(中位数3[2-4]),表明更好的整体性能。值得注意的是,在诱导化疗和手术决策的管理中观察到不一致,如颈部解剖。
    结论:虽然这两个LLM都证明了在头颈部肿瘤学的多学科管理方面有帮助的潜力,某些关键领域的差异突出了进一步完善的必要性。该研究支持AI在增强临床决策中的作用,但也强调了不断更新和验证当前临床标准的必要性,以将AI完全整合到医疗保健实践中。
    OBJECTIVE: This study evaluates the efficacy of two advanced Large Language Models (LLMs), OpenAI\'s ChatGPT 4 and Google\'s Gemini Advanced, in providing treatment recommendations for head and neck oncology cases. The aim is to assess their utility in supporting multidisciplinary oncological evaluations and decision-making processes.
    METHODS: This comparative analysis examined the responses of ChatGPT 4 and Gemini Advanced to five hypothetical cases of head and neck cancer, each representing a different anatomical subsite. The responses were evaluated against the latest National Comprehensive Cancer Network (NCCN) guidelines by two blinded panels using the total disagreement score (TDS) and the artificial intelligence performance instrument (AIPI). Statistical assessments were performed using the Wilcoxon signed-rank test and the Friedman test.
    RESULTS: Both LLMs produced relevant treatment recommendations with ChatGPT 4 generally outperforming Gemini Advanced regarding adherence to guidelines and comprehensive treatment planning. ChatGPT 4 showed higher AIPI scores (median 3 [2-4]) compared to Gemini Advanced (median 2 [2-3]), indicating better overall performance. Notably, inconsistencies were observed in the management of induction chemotherapy and surgical decisions, such as neck dissection.
    CONCLUSIONS: While both LLMs demonstrated the potential to aid in the multidisciplinary management of head and neck oncology, discrepancies in certain critical areas highlight the need for further refinement. The study supports the growing role of AI in enhancing clinical decision-making but also emphasizes the necessity for continuous updates and validation against current clinical standards to integrate AI into healthcare practices fully.
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  • 文章类型: Journal Article
    目的:本研究的目的是通过PCT的发生率和术后吞咽的评估来评估全喉切除术后吻合器咽部闭合的功能结局。此外,该研究旨在评估患者生存率的肿瘤结局.
    方法:这项随机临床试验是对58例接受全喉切除术的晚期喉癌患者进行的。根据喉切除术后咽部修复的方法将患者随机分为两组:手动闭合组(n=28),和订书机组(n=30)。评估和比较功能和肿瘤结果。
    结果:吻合器组的咽瘘发生率明显较低。此外,与手动组相比,吻合器组的手术时间明显缩短,吞咽功能更好。两组之间的生存率没有统计学上的显着差异。
    结论:如果考虑到原发肿瘤的适应症,吻合器是全喉切除术后咽部闭合的可靠方法。缝合器闭合减少了PCF的发生率并减少了手术时间。在不损害肿瘤结果的情况下实现良好的吞咽结果。
    OBJECTIVE: The aim of the current study was to evaluate the functional outcomes of stapler pharyngeal closure after total laryngectomy by the incidence of PCT and assessment of swallowing after surgery. In addition, the study aimed to evaluate the oncological outcomes in terms of patients\' survival rates.
    METHODS: This randomized clinical trial was conducted on 58 patients with advanced laryngeal carcinoma who underwent total laryngectomy. Patients were randomly assigned to two groups according to the method of pharyngeal repair after laryngectomy: manual closure group (n = 28), and stapler group (n = 30). Functional and oncological outcomes were assessed and compared.
    RESULTS: The incidence of pharyngocutaneous fistula was significantly less in the stapler group. Additionally, operative time was significantly shorter and swallowing function was better in the stapler group compared to the manual group. There was no statistically significant difference between groups regarding survival rates.
    CONCLUSIONS: The stapler is a reliable method for pharyngeal closure after total laryngectomy if the limits of its indications regarding the primary tumor are considered. Stapler closure decreases the incidence of PCF and decreases the surgical time. Good swallowing outcomes are achieved without compromising the oncological outcomes.
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  • 文章类型: Case Reports
    喉神经内分泌癌是喉部最常见的非鳞状肿瘤。由于肿瘤的稀有性,病理诊断应通过免疫组织化学证实。
    喉神经内分泌癌(LNEC)是一种罕见的头颈部癌症。文献中很少有起源于声门下喉的低分化神经内分泌癌的病例报道。在这种情况下,我们讨论了一名57岁的患者,有四个月的声音嘶哑病史,新诊断为声门下喉低分化神经内分泌癌。各个NEC组的治疗和预后不同,因此,精确的识别需要考虑显微镜发现和免疫染色分析。免疫组织化学染色显示细胞角蛋白7,突触素,嗜铬粒蛋白,CD56,Ki-67指数为45%。虽然手术通常是所有肿瘤类型的治疗方法,由于手术无效,低分化的NECs推荐化疗放疗。
    UNASSIGNED: Laryngeal neuroendocrine carcinomas are the most common non-squamous neoplasm of the larynx. Due to the rarity of the tumor, pathological diagnosis should be confirmed by immunohistochemistry.
    UNASSIGNED: Laryngeal neuroendocrine carcinomas (LNECs) are a rare cancer of the head and neck. Few case reports of poorly differentiated neuroendocrine carcinoma originating in the subglottic larynx exist within the literature. In this case, we discuss a 57-year-old patient with a history of four-month hoarseness with a newly diagnosed of poorly differentiated neuroendocrine carcinoma in the subglottic larynx. Treatment and prognosis of the various NEC groups differ, so precise identification requires consideration of the microscopic findings and immunostaining analysis. immunohistochemistry staining demonstrated positive result for cytokeratin 7, synaptophysin, chromogranin, CD 56, with the Ki-67 index of45%. Although surgery is usually the treatment for all tumor types, chemo radiotherapy is recommended for poorly differentiated NECs because surgery is ineffective.
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  • 文章类型: Journal Article
    场癌化理论是头颈部癌的重要范例,因为其肿瘤影响以多种方式影响治疗结果。这项研究的目的是评估肿瘤周围粘膜与肿瘤新血管生成过程之间可能的相互联系。本研究纳入了60例晚期喉癌患者。大多数患者表达典型的HIF上调的促血管生成特征,HIF-1α过表达和HIF-2α同种型的正常表达水平几乎完全占优势。值得注意的是,在肿瘤周围良性粘膜中,超过60%的队列也显示出HIF上调的促血管生成特征.此外,与肿瘤组织相比,后一个亚组的HIF-2α上调表型明显偏移,即,与由HIF-1α肿瘤表型主导的情况相反,观察到HIF开关的趋势。ETS-1在肿瘤和肿瘤周围粘膜中存在的促血管生成表型中均显示稳定且相同的显着过表达。在目前的研究中,我们首次报道了与成对的远端喉粘膜相比,晚期喉癌瘤周粘膜中存在异常的促血管生成表达谱。此外,我们描述了这种促血管生成特征的特定表型,该表型与肿瘤组织中存在的表型显着不同,因为我们描述了两种表型,定量和定性。这个发现是癌症的异质性,本身,超出了恶性肿瘤的“经典”边界,这证明了场癌变和癌症的经典标志之一——肿瘤新血管生成的过程之间有很强的联系。
    The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the \"classical\" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.
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