液体活检在卵巢癌中的研究进展

液体活检为无创或微创检测技术,其主要成分包括循环肿瘤细胞(circulating tumor cell, CTCs)、循环肿瘤DNA(circulating tumor DNA, ctDNA)及外泌体(exosomes),具有肿瘤异质性,在肿瘤早期即可作为特异性肿瘤标志物进行筛查诊断。液体活检在卵巢癌的早期诊断、预后评估等方面具有重要研究价值。液体活检不仅操作简便,创伤性小,可重复性高,且时效性强,更能全面反映肿瘤异质性。通过检测患者体液中的CTCs、ctDNA、外泌体即可早期发现和诊断卵巢癌。     

甲基化循环肿瘤DNA的检测及应用

癌症目前仍是医学界面临的第一大难题,其早期诊断、预后风险预测及治疗疗效评估有利于提高患者的生存率.目前临床上诊断癌症主要依靠肿瘤组织病理、内窥镜等检查,但都存在侵入性和异质性的问题.而在肿瘤细胞DNA中发生的分子变化如突变、易位和甲基化等,在循环肿瘤DNA(circulating tumor DNA,ctDNA)中也能...     

循环肿瘤细胞的检测方法

在原发上皮肿瘤形成和生长的早期，肿瘤细胞便可以通过血流播散到远处器官。这些循环肿瘤细胞（circulating tumor cells，CTCs）可以通过不同技术进行富集和检测，其分析被认为是对癌症患者的实时“液体活检”。这种活检能对CTCs特异性亚群进行表征，且有可能为癌症的检测和控制带来革命性的转变。本篇作者将着重讨论当前用于CTCs富集和检测的策略。     

循环肿瘤细胞检测的临床应用及其面临的挑战和对策

循环肿瘤细胞（circulating tumor cells,CTC）是肿瘤发生远处转移的关键环节,也是肿瘤液体活检的主要材料之一,在肿瘤患者的预后判断、疗效预测、疗效评价以及复发转移和耐药机制的研究中都具有重要的临床意义。然而,由于CTC的稀有性、异质性以及转移过程的复杂性等原因,CTC检测的临床应用仍然面临诸多挑战...     

循环肿瘤细胞的检测对乳腺癌诊治意义的研究现状

目前已有证据表明循环肿瘤细胞（circulating tumor cell,CTC）和无病生存期,无进展生存期和总生存期相关。检测外周血循环肿瘤细胞（peripheral blood circulating tumor cells,CTCS）已经成为在癌症诊断中热门领域之一。检测CTC预测癌转移的方法证明优于一些传统的方法,且具有早期、高效、可靠及可重复性好等特点。本文总结国内外乳腺癌循环肿瘤细胞在检测手段及相关临床意义方面的研究进展,以及有关CTC检测项目在研究肿瘤转移过程中的地位、必要性及未来的发展方向。     

ctDNA在结直肠癌诊断中的应用进展于

结直肠癌是世界范围内最为常见的恶性肿瘤之一,早期诊断对于结直肠癌治疗具有重要意义。目前结直肠癌筛查的主要方法包括直肠指检,肠镜和粪便隐血试验等,但这些检测方法具有一定的缺点,基于血液样本的液体活检方法逐渐受到关注。循环肿瘤DNA（Circulatingtumor DNA,ctDNA）因其独特生物学特性成为结直肠癌患者潜在的血循环生物标记物,本文将关注ctDNA在结直肠癌诊断方面的应用。     

循环肿瘤标志物在甲状腺癌临床诊疗中应用的研究进展

目的 总结循环肿瘤标志物应用于甲状腺癌临床诊疗中的研究进展。方法 在中国知网、万方数据库以及PubMed等中英文数据库中,检索2022年7月之前发表的肿瘤标志物与甲状腺癌临床应用的相关文献共568篇,剔除与内容不符、无法获得全文、重复性研究以及较为陈旧的文献,最终纳入63篇文献进行总结和分析。结果 甲状腺癌是临床最常见的内分泌肿瘤,超声引导下细针穿刺细胞学检查（FNAB）是其诊断的金标准,但存在15%~20%的不准确性。近年来,作为一种新型的非侵入性诊断工具,对包括循环肿瘤细胞（CTCs）、细胞游离DNA（cfDNA）/循环肿瘤DNA（ctDNA）、外泌体以及游离的非编码RNAncRNA）等在内的循环肿瘤标志物的检测,在甲状腺乳头状癌和滤泡状癌患者的临床诊疗中发挥了一定的作用,能够在较早期监测到肿瘤进展或复发,从而帮助临床医生制定个体化的治疗方案。然而,关于循环肿瘤标志物与甲状腺髓样癌以及未分化癌的研究仍旧较少,同时ctDNA与非编码RNA（ncRNA）在甲状腺癌临床诊疗中的作用仍不明确,仍需对其分子机制进一步探讨。结论 循环肿瘤标志物检测具有侵袭性小、副作用少、肿瘤异质性代表性强等优势,在甲状腺癌的临床诊疗中具有广泛的应用前景。     

肺癌循环肿瘤源性生物标志物

美国国立卫生研究院生物标志物定义工作组将生物标志物定义为“一种具有能客观测量同时可用于评价一般生物过程、发病过程或医疗干预相关药物反应的指示物”[1]。大量正在进行的肺癌相关研究致力于探讨用于早期诊断和高风险预测的气道上皮细胞、痰液、呼气、尿液和血液中的生物标志物。在此，着重评述肺癌的循环生物标志物，尤其是循环肿瘤细胞（circulating tumor cells，CTCs）与循环核酸（circulating nucleic acids，CNAs）。     

循环肿瘤细胞的生物学和临床意义

循环肿瘤细胞（circulating tumor cells,CTCs）评估为探索肿瘤生物学提供了一种新的方法,CTCs也有可能作为有临床意义的生物标志物。长期以来,人们一直在猜测CTCs的存在以及它们在转移中的作用。近年来,可靠分离CTCs技术的出现,使这个领域重新获得关注。CTCs多常见于恶性肿瘤患者的血液中,在健康志愿者和良性疾病患者的血液中比较罕见[1]。     

循环肿瘤细胞：新的肺癌相关肿瘤标志物

循环肿瘤细胞（circulating tumor cell,CTC）计数与乳腺癌、大肠癌和前列腺癌的无进展生存期（progression free survival,PFS）和总生存期（overall survival,os）不佳相关。在肺癌治疗过程中,需要大量可以监测患者疾病进展的多功能肿瘤生物标志物。研究[1-2]发现,肺癌的主要治疗方法——手术治疗,可引起CTC的增加。这有可能造成不同的残留病灶,即使是在全肿瘤切除的成功病例中也是如此。在有关肺癌的CTC研究中,     

Liquid biopsies

Liquid biopsy is based on minimally invasive blood tests and has a high potential to significantly change the therapeutic strategy in cancer patients, providing an extremely powerful and reliable noninvasive clinical tool for the individual molecular profiling of patients in real time. Liquid biopsy approaches include the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor‐derived extracellular vesicles (EVs) that are shed from primary tumors and their metastatic sites into peripheral blood. The major advantage of liquid biopsy analysis is that it is minimally invasive, and can be serially repeated, thus allowing extracting information from the tumor in real time. Moreover, the identification of predictive biomarkers in peripheral blood that can monitor response to therapy in real time holds a very strong potential for novel approaches in the therapeutic management of cancer patients. In this review, we summarize recent knowledge on CTCs and ctDNA and discuss future trends in the field.     

Liquid biopsy in breast cancer: A comprehensive review

Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free RNA, tumor-educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.     

液体活检在肿瘤监测管理中的应用

目前临床在诊疗过程中,无活检组织样本的情况下,常规使用液体活检检测肿瘤敏感靶点以寻找敏感靶向药。而最新研究中液体活检计算的肿瘤突变负荷（bTMB）可以对PD-1/L1抑制剂进行疗效预测;同时越来越多的研究发现液体活检可以通过对肿瘤分子负荷进行检测分析,用于肿瘤的预后评估,微小残留病灶监测,以及肿瘤的克隆进化分析,这使得液体活检有望在肿瘤诊疗过程中辅助临床进行更全面的监测管理,本文就此做一综述。     

立体定向活检在颅内疑难病变诊断中的临床应用

目的 探讨立体定向活检在颅内疑难病变诊断中的临床应用价值。方法 选取我院2011年3月~2017年3月20例患者全部行立体定向活检术,术前均因临床症状或体征多次接受过CT 、MRI 或MRS等影像学检查, 已明确患者颅内病变, 但未对病理性质确诊, 无法采取有效的治疗方法而接受立体定向活检手术。结果 行立体定向活检术确诊病理诊断,星形细胞瘤Ⅲ级6例,星形细胞瘤Ⅱ级2例,淋巴瘤2例,肺癌脑转移瘤2例,肿瘤放射性坏死灶2例,其它5例（胶质母细胞瘤１例,转移性小细胞恶性肿瘤1例,炎细胞１例,脱髓鞘1例,脑梗塞1例）,性质不明1例,手术活检阳性率95.00%。结论　立体定向活检术具有准确性高、创伤小、并发症少等优点,能够有效的诊断颅内疑难病变,并为下一步治疗提供病理学依据。     

Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA

Plasma of cancer patients contains cell-free tumor DNA that carries information on tumor mutations and tumor burden. Individual mutations have been probed using allele-specific assays, but sequencing of entire genes to detect cancer mutations in circulating DNA has not been demonstrated. We developed a method for tagged-amplicon deep sequencing (TAm-Seq) and screened 5995 genomic bases for low-frequency mutations. Using this method, we identified cancer mutations present in circulating DNA at allele frequencies as low as 2%, with sensitivity and specificity of >97%. We identified mutations throughout the tumor suppressor gene TP53 in circulating DNA from 46 plasma samples of advanced ovarian cancer patients. We demonstrated use of TAm-Seq to noninvasively identify the origin of metastatic relapse in a patient with multiple primary tumors. In another case, we identified in plasma an EGFR mutation not found in an initial ovarian biopsy. We further used TAm-Seq to monitor tumor dynamics, and tracked 10 concomitant mutations in plasma of a metastatic breast cancer patient over 16 months. This low-cost, high-throughput method could facilitate analysis of circulating DNA as a noninvasive "liquid biopsy" for personalized cancer genomics.     

Pulmonary carcinosarcoma: a case report

Pulmonary carcinosarcoma, belonging to sarcomatoid carcinomas, is a quite rare tumor that contains both malignant epithelial and mesenchymal elements. This tumor has different phenotypic characteristics and clinical course compared to non-small cell lung tumors. A case diagnosed as carcinosarcoma is presented and its clinical and pathological features and the differential diagnosis are discussed. The case was a 74-year-old male admitted with shortness of breath and cough. The chest x-ray showed a left lung mass and a bronchoscopic examination was performed. Histopathological examination of the bronchoscopic biopsy showed necrosis and a malignant tumor consisting of diffuse infiltrative anaplastic cells. Surgery was performed and the case was diagnosed as carcinosarcoma in the resection material. Pulmonary carcinosarcoma is a rare lung tumor. Determination of tumoral cells and performing advanced investigations in resection material seem to be relatively easier than in small biopsies. However, this type of tumor can be encountered in small biopsy materials as in the presented case and should be kept in mind in relation to the differential diagnosis as small tissues can have only one, particularly mesenchymal, tumoral component.     

Morbus Whipple Histologische Diagnostik nach der Entdeckung von Tropheryma whippelii

Since the microbiological discovery of Tropheryma whippelii, Whipple's disease has attracted to new attention in clinical medicine. As small intestinal biopsy is the diagnostic procedure, the impact of knowledge about the histopathological features of Whipple's disease and its differential diagnosis has increased. PAS-positive macrophages in the intestinal mucosa are the diagnostic hallmark, but further subtyping of cells is important. In Whipple's disease macrophages with intensely PAS-positive granular particles in the cytoplasm (type 1) should be distinguished from cells with faintly PAS-positive cytoplasm without granular particles (type 3). The latter type of macrophages may persist even for many years but does not affect a diagnosis of intestinal remission. However, as systemic infection with T. whippelii is common, but intestinal biopsy specimens are not representative for other organs, additional investigations are performed. These include analysis of the cerebrospinal fluid by means of cytology and polymerase chain reaction, even in patients without neurological symptoms. For ascertaining eradication of T. whippelii in the cerebrospinal fluid, polymerase chain reaction is more reliable than cytology.     

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Recently, many genome‐wide profiling studies provided insights into the molecular make‐up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue‐based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal‐invasive ‘liquid biopsy’. Fragments of circulating cell‐free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre‐analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR‐based single locus assays to genome‐wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre‐analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.