Oesophageal cancer

食管癌
  • 文章类型: Journal Article
    食管癌(OC)是一种常见的恶性肿瘤,对个体构成重大威胁。目前主流的检测方法是内窥镜,这需要专业的操作人员和昂贵的仪器。因此,发展一个快速,易于操作,和低成本的检测方法。在这项研究中,使用氧化铈模拟酶成功构建了RNA比色生物传感器。传感器构建在96孔板上,当存在靶RNA时,用DNA-RNA-DNA复合物固定在微量滴定孔中。这种固定是基于碱基互补配对的原理。固定化CeO2具有催化3,3'发蓝的独特优势,5,5'-四甲基联苯胺(TMB)直接在微量滴定孔中不需要任何额外的氧化剂。该性质允许RNA的检测,并且使得多个样品测定的可视化成为可能。此外,RNA比色传感器显示出良好的选择性,抗干扰性,和高稳定性。在最优条件下,传感器的线性范围为10-13至10-9M,检测限为33.26fM。因此,本研究为食管癌筛查提供了一种新的检测方法。
    Oesophageal cancer (OC) is a prevalent malignant tumor that poses a significant threat to individuals. Current mainstream detection method is endoscopy, which requires professional operators and expensive instruments. Therefore, it is crucial to develop a rapid, easy-to-operate, and low-cost detection method. In this study, an RNA colorimetric biosensor was successfully constructed using cerium oxide mimetic enzyme. The sensor is constructed on 96-well plates, which are immobilized with DNA-RNA-DNA complexes in microtiter wells when target RNA is present. This immobilization is based on the principle of base complementary pairing. The CeO2 immobilized has the unique advantage of catalyzing the bluing of 3,3\',5,5\'-tetramethylbenzidine (TMB) directly without the need any additional oxidant in microtiter wells. This property allows for the detection of RNA and enables the visualization of multiple sample assays. Furthermore, the RNA colorimetric sensor demonstrates good selectivity, immunity to interference, and high stability. Under optimal conditions, the sensor exhibited linearity in the range of 10-13 to 10-9 M with a detection limit of 33.26 fM. Therefore, this study presents a new detection method for oesophageal cancer screening.
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  • 文章类型: Journal Article
    背景:肌肉骨化是衡量骨骼肌质量的指标,并且在计算机断层扫描上很容易识别。术前肌萎缩对根治性食管切除术后预后的影响尚不确定。我们的目的是将CT上的肌萎缩症的存在与围手术期发病率相关联,死亡率,3个食道癌中心的澳大利亚人群食管切除术后的生存结局。
    方法:对三个中心的所有接受根治性食管癌切除术的患者进行回顾性分析。术前计算机断层扫描(CT)扫描的放射学评估用于确定是否存在肌骨化病。结果测量包括围手术期并发症发生率,总生存率,和无病生存。
    结果:462例患者纳入分析(78.4%为男性,中位年龄67岁)。353例(76.4%)患者在CT上有肌骨形成。肌肉骨质疏松患者的主要并发症(Clavien-Dindo3b或更高)发生率较高(24.9%vs.14.7%,p=0.026),和更高的30天死亡率(4%vs.0%,p=0.048)与正常骨骼肌衰减的患者相比。在多变量分析中,肌萎缩与主要并发症相关(HR1.906,95%CI1.057-3.437;p=0.032)。肌骨化性和非肌骨化性患者的总生存期没有差异(59vs.56个月,p=0.465),无病生存率也没有差异(39vs.42个月,p=0.172)。
    结论:影像学检查显示肌骨形成与主要并发症和30天死亡率的风险增加相关。识别肌肉骨化可以是术前营养评估和预后的辅助手段。促进早期识别有并发症风险的患者。
    BACKGROUND: Myosteatosis is a measure of skeletal muscle quality, and is readily identifiable on computed tomography. The effect of the presence of preoperative myosteatosis on outcomes following radical oesophagectomy is uncertain. We aimed to correlate the presence of myosteatosis on CT to perioperative morbidity, mortality, and survival outcomes following oesophagectomy in an Australian population across three oesophageal cancer centres.
    METHODS: A retrospective analysis was performed of all patients undergoing radical oesophagectomy for cancer across three centres. Radiologic assessment of preoperative computed tomography (CT) scans was used to determine the presence of myosteatosis. Outcomes measured included perioperative complication rate, overall survival, and disease-free survival.
    RESULTS: 462 patients were included for analysis (78.4% male, median age 67 years). 353 (76.4%) patients had myosteatosis on CT. Myosteatotic patients had a higher rate of major (Clavien-Dindo 3b or higher) complication (24.9% vs. 14.7%, p=0.026), and a higher rate of 30-day mortality (4% vs. 0%, p=0.048) compared to patients with normal skeletal muscle attenuation. Myosteatosis was associated with major complication on multivariate analysis (HR 1.906, 95% CI 1.057-3.437; p=0.032). There was no difference in overall survival between myosteatotic and non-myosteatotic patients (59 vs. 56 months, p=0.465), nor was there a difference in disease-free survival (39 vs. 42 months, p=0.172).
    CONCLUSIONS: The presence of myosteatosis on radiologic imaging was associated with increased risk of major complications and 30-day mortality. Identifying myosteatosis can be an adjunct to preoperative nutritional assessment and prognostication, facilitating early recognition of patients at risk of complications.
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  • 文章类型: Clinical Trial Protocol
    背景:本研究的目的是研究长期血栓预防是否能降低食管癌手术治疗后血栓形成的风险。研究结果有望为食管癌手术后的血栓预防提供指导。观点是降低这一危重病人群体的发病率和死亡率。血栓形成是仅次于癌症本身的第二大癌症死亡原因。血栓形成的风险取决于癌症类型,上消化道癌症被认为是高风险的。当患者接受手术时,这种风险进一步增加。然而,只有少数研究调查了食管癌患者围手术期和术后凝血功能.由于知识的缺乏,目前,从手术到出院(大约10天),每天的预防仅限于5000IU(国际单位)低分子量肝素,而胃癌患者接受30天的治疗。本研究检查了30天的治疗是否优越和安全,与目前的标准治疗相比。
    方法:本研究是一项随机对照试验。包容正在进行中,我们的目标是包括100名患者。在手术前后抽取血样,并且广泛检查凝血。主要终点是干预组和标准组之间手术后30天凝血酶原片段1+2(F1+2)的血浆水平的差异。此外,对患者进行超声检查,以筛查无症状静脉血栓形成事件(VTE).次要终点是出血的发生率,手术后1年30天,有症状和无症状的VTE和死亡率。
    结论:该研究将为食管癌患者围手术期凝血情况和VTE风险提供有价值的信息。该研究旨在帮助优化术后血栓预防,我们的观点是降低这一高危患者人群的发病率和死亡率。
    背景:该试验于2021年6月30日在ID为2021-001335-24的欧盟临床试验注册中心进行了前瞻性注册,并在ClinicalTrials.gov上进行了注册,研究标识符为NCT05067153。
    BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment.
    METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery.
    CONCLUSIONS: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population.
    BACKGROUND: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.
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  • 文章类型: Journal Article
    目的:了解食管腺癌(OAC)的CD8+肿瘤浸润淋巴细胞(TIL)区隔与淋巴细胞耗竭的关系,组织驻留,并确定对治疗的不同反应背后的可能原因。
    方法:通过流式细胞术评估了44例接受OAC根治性切除术的患者的肿瘤样本中是否存在抗原经历的TIL以及激活和耗尽的标志物。对PD-1和CD39阳性OACTIL的群体进行排序,和使用改进的SmartSeq2方案进行的批量RNA测序。完成功能的流式细胞术评估。
    结果:经历CD8+OACTILs的抗原比例较高与手术后生存率提高有关;而,在这些TIL中,PD-1和CD39的高双阳性(DP)也与结局显著相关.这些DPTIL具有少数群体,其对耗竭标记TIM3和LAG3呈阳性。对PD-1和CD39DPTIL的转录组学评估表明,与其他癌症生存率提高相关的组织常驻记忆T淋巴细胞(TRM)表型富集。通过流式细胞术对典型TRM标记CD103的阳性增强。这个群体在他们的转录组学谱中都表现出维持的功能能力,在流式细胞术评估中,以及保留的增殖能力。
    结论:切除的OAC被PD-1和CD39DPTIL不同程度地浸润,淋巴细胞中的丰富与存活率的提高有关。这个DP人口增加了,但仍然谦虚,与DN相比,TIM3和LAG3阳性的频率,并且与功能性有能力的TRM表型保持一致。
    OBJECTIVE: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.
    METHODS: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed.
    RESULTS: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity.
    CONCLUSIONS: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.
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  • 文章类型: Journal Article
    我们打算从患者报告的角度探讨韧性和社会支持的不同来源对症状干扰与生活满意度之间关系的连锁调解作用。
    使用四种有效的量表对食管切除术后的二百二十六例患者进行了调查,以估计症状干扰,弹性,不同的社会支持来源,和生活满意度。链中介分析使用SPSS过程宏模型6进行。
    中介分析表明,症状干扰通过两个重要的中介途径间接影响生活满意度:(i)弹性(B=-0.138,95%CI:-0.194至-0.091);(ii)涉及弹性和家庭支持的链条中介(B=-0.049,95%CI:-0.073至-0.026)。令人惊讶的是,家庭支持的中介途径不显著。
    对弹性和家庭支持的干预可以减轻食道切除术后患者症状干扰的不利影响,提高生活满意度。其中,在利用社会资源方面,复原力可能比家庭支持更为重要。
    UNASSIGNED: We intended to explore the chain mediation role of resilience and different sources of social support on the relationship between symptom interference and life satisfaction from the patient-reported perspective.
    UNASSIGNED: Two hundred and twenty-six patients after esophagectomy were investigated using four validated scales to estimate the symptom interference, resilience, different sources of social support, and life satisfaction. The chain mediation analysis was conducted using SPSS PROCESS Macro Model 6.
    UNASSIGNED: Mediation analysis showed that symptom interference indirectly influenced life satisfaction through two significant mediating pathways: (i) resilience (B = -0.138, 95% CI: -0.194 to -0.091); (ii) the chain mediators involving in resilience and family support (B = -0.049, 95% CI: -0.073 to -0.026). Surprisingly, the mediating pathway of family support was not significant.
    UNASSIGNED: Interventions for resilience and family support could mitigate the adverse effects of symptom interference in patients after esophagectomy, improving life satisfaction. Of these, resilience may be more critical in terms of the utilization of social resources than family support.
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  • 文章类型: Journal Article
    目的:评估食管癌患者术后早期核心症状及其与心理弹性的关系。
    背景:食管癌患者在术后早期面临大量严重症状,需要制定有效的症状管理方案。通过网络分析识别核心症状有助于准确的患者护理。
    方法:多中心横断面研究。
    方法:于2022年8月至2023年8月在安徽省三家医院进行了横断面调查,中国。本研究共招募469名患者,418名(89.1%)患者完成了本研究。使用网络分析发现食管癌患者术后早期核心症状。采用多元线性回归分析影响核心症状的韧性因素。
    结果:悲伤是食管癌患者术后早期最核心的症状(rs=1.41),其次是切口疼痛,休息时呼吸困难(rs=1.20,rs=1.08)。弹性与患者的悲伤情绪显著相关,乐观对悲伤的影响最大(p<0.01)。
    结论:悲伤是患者术后早期最核心的症状,应特别注意提高患者的心理弹性水平。术后早期局部症状和功能障碍应协同治疗。
    结论:本研究确定了食管癌患者术后早期的核心症状及其与心理弹性的关系。症状为患者术后早期的主要核心症状,这是悲伤,与韧性显著相关。可以针对患者的核心术后症状进行精确的干预,这有助于提高症状管理的有效性。
    我们已遵守相关的EQUATOR研究报告清单。
    研究中没有患者或公众的贡献。
    OBJECTIVE: To assess early postoperative core symptoms in oesophageal cancer patients and their relationship with resilience.
    BACKGROUND: Patients with oesophageal cancer face a high number of severe symptoms in the early post-operative period and require the development of an effective symptom management programme. Identifying core symptoms through network analysis helps in accurate patient care.
    METHODS: A multicentre cross-sectional study.
    METHODS: A cross-sectional survey was conducted from August 2022 to August 2023 at three hospitals in Anhui Province, China. A total of 469 patients were recruited for this study and 418 (89.1%) patients completed this investigation. Using network analysis to find early post-operative core symptoms in oesophageal cancer patients. Multiple linear regression was used to analyse resilience factors affecting core symptoms.
    RESULTS: Sadness was the most core symptom in oesophageal cancer patients in the early post-operative period (rs = 1.41), followed by incision pain and difficulty breathing while resting (rs = 1.20, rs = 1.08). Resilience was significantly associated with patients\' feelings of sadness, with optimism having the greatest impact on sadness (p < .01).
    CONCLUSIONS: Sadness is the most core symptom in patients in the early post-operative period and special attention should be paid to improving their level of resilience. Local symptoms and dysfunction in the early post-operative period should be treated in a synergistic manner.
    CONCLUSIONS: This study identifies core symptoms and their relationship to resilience in patients with oesophageal cancer in the early post-operative period. Symptoms as the main core symptom in patients in the early post-operative period, which was sadness and was significantly associated with resilience. Precise interventions can be made to target patients\' core post-operative symptoms, which can help improve the effectiveness of symptom management.
    UNASSIGNED: We have complied with the relevant EQUATOR research reporting checklist.
    UNASSIGNED: No patient or public contribution in the study.
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  • 文章类型: Journal Article
    目的:胸外科手术患者并发症发生率高。尚不确定术前健康相关生活质量(HRQOL)测量是否可以预测术后并发症风险较高的患者。这项研究的目的是确定胸外科手术患者术前HRQOL与术后并发症之间的关系。
    方法:这是一项前瞻性收集数据的回顾性队列研究。包括2018年1月至2019年1月在加拿大三级护理中心接受择期胸外科手术的连续患者。使用Euroqol-5维度(EQ-5D)调查测量患者HRQOL。使用渥太华胸腔疾病发病率和死亡率系统记录并发症。进行单变量和多变量分析。
    结果:在进行的515次手术中,133例(25.8%)患者经历了至少一次术后并发症。345例(67.0%)患者因恶性肿瘤接受手术治疗。271名(52.7%)至310名(60.2%)患者在每个时间点经历疼痛/不适。在多变量分析中,较低的术前EQ-5D视觉模拟评分与术后并发症显著相关[调整比值比0.97,95%置信区间0.95-0.99;p=0.01].恶性肿瘤的存在与并发症无关(p=0.68)。
    结论:术前自我报告HRQOL可以预测胸外科手术患者术后并发症的发生率。术前HRQOL评估可能有助于识别发生并发症风险较高的患者。这些发现可用于指导HRQOL领域的术前风险缓解策略,如疼痛。应识别患者HRQOL的完整围手术期轨迹,以识别具有共同危险因素的患者亚群。
    OBJECTIVE: Patients undergoing thoracic surgery experience high complication rates. It is uncertain whether preoperative health-related quality of life (HRQOL) measurements can predict patients at higher risk for postoperative complications. The objective of this study was to determine the association between preoperative HRQOL and postoperative complications among patients undergoing thoracic surgery.
    METHODS: This was a retrospective cohort study of prospectively collected data. Consecutive patients undergoing elective thoracic surgery at a Canadian tertiary care centre between January 2018 and January 2019 were included. Patient HRQOL was measured using the Euroqol-5 Dimension (EQ-5D) survey. Complications were recorded using the Ottawa Thoracic Morbidity and Mortality system. Uni- and multivariable analysis were performed.
    RESULTS: Of 515 surgeries performed, 133 (25.8%) patients experienced at least 1 postoperative complication; 345 (67.0%) patients underwent surgery for malignancy. A range of 271 (52.7%) to 310 (60.2%) patients experienced pain/discomfort at each timepoint. On multivariable analysis, lower preoperative EQ-5D visual analogue scale scores were significantly associated with postoperative complications (adjusted odds ratio 0.97, 95% confidence interval 0.95-0.99; P = 0.01). Presence of malignancy was not independently associated with complications (P = 0.68).
    CONCLUSIONS: Self-reported preoperative HRQOL can predict incidence of postoperative complications among patients undergoing thoracic surgery. Assessments of preoperative HRQOL may help identify patients at higher risk for developing complications. These findings could be used to direct preoperative risk-mitigation strategies in areas of HRQOL where patients suffer most, such as pain. The full perioperative trajectory of patient HRQOL should be discerned to identify subsets of patients who share common risk factors.
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  • 文章类型: Journal Article
    背景:食道,胃食管,胃恶性肿瘤通常在局部晚期诊断,建议采用多模式治疗以增加生存机会。然而,考虑到治疗反应的显著差异,明确必须完善患者分层.这篇叙述性综述的目的是探索现有证据和影像组学在改善胃胃癌分期和预测治疗反应方面的潜力。
    方法:本文的参考文献是通过MEDLINE(PubMed)和Scopus搜索确定的,其术语为“radiomics”,\"纹理分析\",“食道癌”,“胃食管结合部癌”,“食管胃结合部癌”,“胃癌”,“胃癌”,\"暂存\",和“治疗反应”,直至2024年5月。
    结果:在所有成像方式下,Radiomics被证明可有效改善食管癌和胃癌的疾病分期和治疗反应预测(TC,MRI,和18F-FDGPET/CT)。关于影像组学应用于胃食管交界处癌的文献资料非常匮乏。与单一放射学方法相比,当整合不同的成像模式时,以及与仅使用放射组学签名相比,将临床与放射组学特征相结合时,放射组学模型表现更好。
    结论:影像组学在局部晚期胃腺癌患者的非侵入性分期和预测术前治疗反应方面具有潜力。作为未来的视角,将分子亚组分析纳入临床和影像学特征甚至可能提高这些预测和预后模型的有效性.
    BACKGROUND: Oesophageal, gastroesophageal, and gastric malignancies are often diagnosed at locally advanced stage and multimodal therapy is recommended to increase the chances of survival. However, given the significant variation in treatment response, there is a clear imperative to refine patient stratification. The aim of this narrative review was to explore the existing evidence and the potential of radiomics to improve staging and prediction of treatment response of oesogastric cancers.
    METHODS: The references for this review article were identified via MEDLINE (PubMed) and Scopus searches with the terms \"radiomics\", \"texture analysis\", \"oesophageal cancer\", \"gastroesophageal junction cancer\", \"oesophagogastric junction cancer\", \"gastric cancer\", \"stomach cancer\", \"staging\", and \"treatment response\" until May 2024.
    RESULTS: Radiomics proved to be effective in improving disease staging and prediction of treatment response for both oesophageal and gastric cancer with all imaging modalities (TC, MRI, and 18F-FDG PET/CT). The literature data on the application of radiomics to gastroesophageal junction cancer are very scarce. Radiomics models perform better when integrating different imaging modalities compared to a single radiology method and when combining clinical to radiomics features compared to only a radiomics signature.
    CONCLUSIONS: Radiomics shows potential in noninvasive staging and predicting response to preoperative therapy among patients with locally advanced oesogastric cancer. As a future perspective, the incorporation of molecular subgroup analysis to clinical and radiomic features may even increase the effectiveness of these predictive and prognostic models.
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  • 文章类型: Journal Article
    背景:临床医生主导的肿瘤决策质量控制对于优化患者护理至关重要。可解释的人工智能(XAI)技术提供数据驱动的方法来揭示临床变量如何影响这一决策。我们应用了全球XAI技术来检查通过机器学习(ML)模型映射时关键临床决策驱动因素的影响。多学科团队(MDT)接受不同食道癌(OC)治疗方式的可能性。
    方法:回顾性分析2010年至2022年在我们三级单位管理的893名OC患者,使用随机森林(RF)分类器来预测由MDT确定的四种可能的治疗途径:新辅助化疗后手术(NACT+S),新辅助放化疗后手术(NACRT+S),单独手术,和姑息管理。变量重要性和部分依赖性(PD)分析然后检查ML模型内的靶向高级临床变量对治疗决策的影响,作为MDT决策动态的替代模型。
    结果:在已知用于确定治疗方法的指南变量中,如肿瘤淋巴结转移(TNM)分期,在变量重要性分析中,年龄也被证明对射频模型非常重要(占总重要性的16.1%)。PD随后显示,所有治疗方式的预测概率在75年后均显着变化(p<0.001)。对于75-85岁的患者,单独手术和姑息治疗的可能性增加,但对于NACT/NACRT则降低。表现状况将患者分为两组,这影响了所有与年龄相关的预测结果。
    结论:XAI技术描述了临床因素与OC治疗决定之间的关系。根据我们的模型,这些技术将高龄识别为严重影响决策的因素,在具有特定肿瘤特征的患者中具有更大的作用。这种研究方法为在AI驱动的决策支持时代探索基于团队的决策中的意识/潜意识偏见和询问不一致提供了手段。
    BACKGROUND: Clinician-led quality control into oncological decision-making is crucial for optimising patient care. Explainable artificial intelligence (XAI) techniques provide data-driven approaches to unravel how clinical variables influence this decision-making. We applied global XAI techniques to examine the impact of key clinical decision-drivers when mapped by a machine learning (ML) model, on the likelihood of receiving different oesophageal cancer (OC) treatment modalities by the multidisciplinary team (MDT).
    METHODS: Retrospective analysis of 893 OC patients managed between 2010 and 2022 at our tertiary unit, used a random forests (RF) classifier to predict four possible treatment pathways as determined by the MDT: neoadjuvant chemotherapy followed by surgery (NACT + S), neoadjuvant chemoradiotherapy followed by surgery (NACRT + S), surgery-alone, and palliative management. Variable importance and partial dependence (PD) analyses then examined the influence of targeted high-ranking clinical variables within the ML model on treatment decisions as a surrogate model of the MDT decision-making dynamic.
    RESULTS: Amongst guideline-variables known to determine treatments, such as Tumour-Node-Metastasis (TNM) staging, age also proved highly important to the RF model (16.1 % of total importance) on variable importance analysis. PD subsequently revealed that predicted probabilities for all treatment modalities change significantly after 75 years (p < 0.001). Likelihood of surgery-alone and palliative therapies increased for patients aged 75-85yrs but lowered for NACT/NACRT. Performance status divided patients into two clusters which influenced all predicted outcomes in conjunction with age.
    CONCLUSIONS: XAI techniques delineate the relationship between clinical factors and OC treatment decisions. These techniques identify advanced age as heavily influencing decisions based on our model with a greater role in patients with specific tumour characteristics. This study methodology provides the means for exploring conscious/subconscious bias and interrogating inconsistencies in team-based decision-making within the era of AI-driven decision support.
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  • 文章类型: Journal Article
    背景:食管癌仍然是一种具有挑战性的疾病,死亡率高,治疗选择少。鉴于这些困难,表观遗传药物已成为患者护理的潜在替代品。这项研究的目标是评估Panobinostat治疗的效果和生物学后果,HDAC(组蛋白去乙酰化酶)抑制剂已被批准用于多发性骨髓瘤患者的治疗,在正常和恶性来源的食管细胞系中,后者代表了两种主要的组织学亚型:腺癌和鳞状细胞癌。
    结果:Panobinostat治疗抑制生长并阻碍增殖,食管癌细胞的集落形成和侵袭。考虑HDAC组织表达,与肿瘤组织相比,HDAC1在正常食管上皮中显著上调,而HDAC3与非恶性粘膜相比在食管癌中过度表达。在正常组织和肿瘤组织之间没有观察到HDAC2和HDAC8表达的差异。
    结论:Panobinostat暴露可有效损害食管癌细胞的恶性特征。因为HDAC3在食道肿瘤样本中显示过表达,这种表观遗传药物可能是食管癌患者的替代治疗选择.
    BACKGROUND: Oesophageal cancer remains a challenging disease with high mortality rates and few therapeutic options. In view of these difficulties, epigenetic drugs have emerged as potential alternatives for patient care. The goal of this study was to evaluate the effect and biological consequences of Panobinostat treatment, an HDAC (histone deacetylase) inhibitor already approved for treatment of patients with multiple myeloma, in oesophageal cell lines of normal and malignant origin, with the latter being representative of the two main histological subtypes: adenocarcinoma and squamous cell carcinoma.
    RESULTS: Panobinostat treatment inhibited growth and hindered proliferation, colony formation and invasion of oesophageal cancer cells. Considering HDAC tissue expression, HDAC1 was significantly upregulated in normal oesophageal epithelium in comparison with tumour tissue, whereas HDAC3 was overexpressed in oesophageal cancer compared to non-malignant mucosa. No differences between normal and tumour tissue were observed for HDAC2 and HDAC8 expression.
    CONCLUSIONS: Panobinostat exposure effectively impaired malignant features of oesophageal cancer cells. Because HDAC3 was shown to be overexpressed in oesophageal tumour samples, this epigenetic drug may represent an alternative therapeutic option for oesophageal cancer patients.
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