甲状腺癌分子标志物研究进展

近年来检出的甲状腺结节患者越来越多,多数甲状腺结节是良性的,可以采取保守治疗,但有5%~10%的甲状腺结节是恶性的,需要早期手术治疗,才能获得良好的预后。但是一般良、恶性结节的症状和体征无明显区别,极易误诊。目前甲状腺细针穿刺抽吸检查在一定程度上可以提高甲状腺癌诊断的准确性,但仍有部分不能明确诊断,存在一定的局限性。近年的研究发现大部分甲状腺癌存在一种或几种基因上的异常,而这些基因异常可作为潜在的标志物应用于甲状腺的诊断,也可以对患者的预后进行预测,还可以当作治疗靶点,对临床具有重要意义。本文主要对甲状腺癌新的潜在分子标志物研究进展展开综述。     

Molecular classification of gastric cancer

Introduction: Gastric cancer is among the most common cancers worldwide. Despite declining incidences, the prognosis remains dismal in Western countries and is better in Asian countries with national cancer screening programs. Complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. Survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative chemotherapy. However, the identification and usage of novel predictive and diagnostic targets is urgently needed.

Areas covered: Recent comprehensive molecular profiling of gastric cancer proposed four molecular subtypes, i.e. Epstein-Barr virus-associated, microsatellite instable, chromosomal instable and genomically stable carcinomas. The new molecular classification will spur clinical trials exploring novel targeted therapeutics. This review summarizes recent advancements of the molecular classification, and based on that, putative pitfalls for the development of tissue-based companion diagnostics, i.e. prevalence of actionable targets and therapeutic efficacy, tumor heterogeneity and tumor evolution, impact of ethnicity on gastric cancer biology, and standards of care in the East and West.

Expert commentary: The overall low prevalence of actionable targets and tumor heterogeneity are the two main obstacles of precision medicine for gastric cancer.     

Predictive molecular markers for the treatment with immune checkpoint inhibitors in colorectal cancer

Colorectal cancer is one of the most common malignant tumors and, hence, has become one of the most important public health issues in the world. Treatment with immune checkpoint inhibitors (ICIs) successfully improves the survival rate of patients with melanoma, non‐small‐cell lung cancer, and other malignancies, and its application in metastatic colorectal cancer is being actively explored. However, a few patients develop drug resistance. Predictive molecular markers are important tools to precisely screen patient groups that can benefit from treatment with ICIs. The current article focused on certain important predictive molecular markers for ICI treatment in colorectal cancer, including not only some of the mature molecular markers, such as deficient mismatch repair (d‐MMR), microsatellite instability‐high (MSI‐H), tumor mutational burden (TMB), programmed death‐ligand‐1 (PD‐L1), tumor immune microenvironment (TiME), and tumor‐infiltrating lymphocytes (TILs), but also some of the novel molecular markers, such as DNA polymerase epsilon (POLE), polymerase delta 1 (POLD1), circulating tumor DNA (ctDNA), and consensus molecular subtypes (CMS). We have reviewed these markers in‐depth and presented the results from certain important studies, which suggest their applicability in CRC and indicate their advantages and disadvantages. We hope this article is helpful for clinicians and researchers to systematically understand these markers and can guide the treatment of colorectal cancer.     

Promising immunotherapies for esophageal cancer

Introduction: Esophageal cancer (EC) is the eighth most common cancer in the world, and the prognosis of EC is still poor. Although immunotherapy has been developed in melanoma and lung cancer, it is also expected to show efficacy in EC. Currently, several clinical trials are ongoing to evaluate the safety and efficacy of immunotherapies, immune checkpoint inhibitors, adoptive T cell transfer, and therapeutic cancer vaccines in EC.

Areas covered: This review provides an overview and the status of immunotherapy in EC. Clinical significance of molecules related immune checkpoints, especially PD-1 and PD-L1 is presented and the designs, results and future directions of clinical trials using immunotherapy in EC are provided.

Expert opinion: To bring immunotherapy to the forefront of treatment for EC, it is necessary to select patients who can obtain a high efficacy of immunotherapy and to also elucidate the correct timing for administration. Moreover, combination therapies of immunotherapy with existing chemotherapy or radiation or other immunotherapy with different mechanisms of action must be evaluated to achieve excellent outcomes in patients with EC.     

食管癌术中医源性脾损伤的预防及临床对策(附21例报告)

目的探讨食管癌手术中脾脏损伤的预防措施及发生后的临床对策。方法总结分析一组共492例食管癌根治术中发生脾脏损伤共21例患者的临床资料。结果21例患者中Ⅰ度损伤12例,Ⅱ度损伤7例,Ⅲ度损伤2例;行各种方式的脾脏修补术17例,无法保留脾脏行脾切除者4例;术后发生脾窝感染1例,血小板增高给予抗凝治疗1例;所有患者无术后腹腔出血,均痊愈出院。结论食管癌手术中需防止脾脏的损伤,一旦发生需采取合理的措施防止损伤扩大,尽量避免脾脏切除,以利于术后恢复。     

结直肠癌分子分型及分子标志物的研究进展

结直肠癌(colorectal cancer, CRC)是生物学高度异质性的肿瘤,对其进行分子分型有助于识别肿瘤组织来源、预测肿瘤进展或转移复发风险,且是个体化精准治疗的必要前提。分子标志物RAS、BRAF、PI3KCA和HER-2能协助CRC的诊断、临床分期、判断预后和指导临床治疗。本文就近年来CRC分子分型及其分子标志物的研究作一综述。     

恶性胸膜间皮瘤分子标志物研究进展

恶性胸膜间皮瘤(MPM)是一种罕见但高度恶性的肿瘤,其发病率在全球范围内逐渐上升。但MPM早期临床症状不典型,诊断方法缺乏特异性,患者确诊时往往已处于疾病晚期,导致该病的预后极差。因此更好地理解MPM肿瘤分子和细胞过程中高度特异性分子标志物或新的诊断工具显得愈发重要。本文阐述了目前临床对于MPM分子标志物的研究进展,尽管MPM相关信号功能的精确机制仍未完全了解,但本文仍可为进一步的研究指明研究方向,为MPM的临床诊断及治疗提供依据。     

表皮生长因子受体在食管癌中的表达及临床意义

目的探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)与食管癌临床病理特征及预后的关系。方法采用免疫组织化学法检测92份食管癌组织,26份Ⅰ度不典型增生组织,17份Ⅱ/Ⅲ度不典型增生组织,89份正常食管黏膜组织(正常组)的EGFR表达情况,并分析EGFR与临床组织病理特征及预后的关系。结果正常组、Ⅰ度不典型增生组、Ⅱ/Ⅲ度不典型增生组、食管癌组中EGFR过表达率分别为0(0/89),19.23%(5/26),58.82%(10/17),69.57%(64/92);EGFR过表达在不同浸润深度,是否伴淋巴结转移上差异均有统计学意义(P<0.05);EGFR过表达阳性组与阴性组生存曲线差异有统计学意义(P<0.05)。结论 EGFR过表达与食管癌发生、发展及预后密切相关。     

ErbB family receptor inhibitors as therapeutic agents in breast cancer: current status and future clinical perspective

Breast cancer is the most common cancer diagnosed in women and the second most common cause of female cancer-related deaths, with more than one million new cases diagnosed per year throughout the world. With the recent advances in the knowledge of cellular processes and signaling pathways involved in the pathogenesis of breast cancer, the current focus of researchers and clinicians is to develop novel treatment strategies that can be included in the armamentarium against breast cancer. With the failure of endocrine-targeted therapy and the development of resistance to existing chemotherapy, the most explored pathway as next generation target for breast cancer therapy has been the epidermal growth factor receptor (EGFR) (ErbB-1)/herceptin-2 (HER-2) (ErbB-2) pathway. This review focuses on the rationale for targeting members of ErbB receptor family and numerous agents that are in use for inhibiting the pathway. The mechanism of action, preclinical and clinical trial data of the agents that are in use for targeting the EGFR/HER-2 pathway and the current status, thereof, have been discussed in detail. In addition, the future clinical trial promises these agents hold either as monotherapy or as combination therapy with conventional agents or with other antisignaling agents have been pondered, so as to provide better and more efficacious treatment strategies for breast cancer patients.     

食管覆膜支架置入术和球囊扩张术在治疗中晚期食管癌中的临床价值探讨

目的:探究中晚期食道癌应用食管覆膜支架置入和球囊扩张术治疗的临床应用价值。方法:对我院收治中晚期食道癌患者110例进行回顾性分析,治疗前本组病例均有病理活检,患者均为不能手术或拒绝手术的患者。所有患者术前均行X线检查,确定病变部位、狭窄长度及与周围组织关系,本组病例均有在术前或术后配合化疗或放射治疗的情况。对110例患者分组,30例患者置入覆膜支架,对30例患者进行球囊扩张,对50例患者不分先后做了食管覆膜支架置入术和球囊扩张术。以术后狭窄扩张效果、生存质量及相关并发症进行比较分析。结果:支架置入成功率100%,平均生存期12个月,食道球囊扩张均经1~3次扩张达到预期效果,成功率70%,生存率9个月,食管覆膜支架置入术联合球囊扩张术治疗中晚期食道癌,总有效率100%,生存期平均16个月。结论:食管覆膜支架置入术联合球囊扩张术,在治疗中晚期食管癌能相对延长患者生存时间、提高生存质量方面明显优于单纯食道食管覆膜支架置入术及单纯球囊扩张术,患者疗效更高,具有理想的临床价值。     

食管癌中C-erbB-2,bc1-2,mdr-1的表达与同步放化疗疗效及预后关系的研究

目的：研究食管癌中C-erbB-2，be1-2，mdr-1表达与其同步放化疗疗效及预后的相关性。方法：应用免疫组化技术（S-P法）对187例食管鳞癌进行初治前、治疗后复发或转移不同阶段胃镜活检标本中C-erbB-2，be1-2，mdr-1三种基因蛋白表达的检测。初治均按拟定的统一放化疗方案进行：DF方案化疗同步超分割放疗。结果：187例食管鳞癌细胞中，C-erbB-2，be1-2，mdr-1阳性表达分别为48．7％，55．1％和42．2％，治疗后完全缓解68例（36．4％），部分缓解81例（43、3％），稳定31例（16．6％），进展7例（3、7％）。C-erbB-2阴性者疾病进展时间在24～36个月者38例（39．6％），〈12个月者占19、7％；C-erbB-2阳性者，疾病进展时间〈12个月者比例较高；强阳性者所占比例最高达18／42（42．9％）。C-erbB-2与mdr-1同时阳性表达疾病进展时间〈12个月者比例较高（45．7％）；二者均阴性疾病进展时间在24～36个月所占比例较高（46．2％）。bcl-2强阳性完全缓解占21、3％，阴性完全缓解达50．0％。结论：本实验有希望为食管癌不同阶段制定个体化治疗方案，为观察疗效和预后提供更科学合理的依据。     

乳腺癌DCE-MRI参数及ADC与病理分子预后标记物的相关性分析

目的分析乳腺癌动态对比增强磁共振成像(dynamic contrast-enhanced magnetic resonance imaging,DCE-MRI)参数、表观扩散系数(apparent diffusion coefficient,ADC)与病理分子预后标记物的相关性。材料与方法回顾性分析我院106例乳腺癌患者临床资料,分别比较雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、细胞增殖抗原Ki67及雄激素受体(androgen receptor,AR)阳性表达与阴性表达者DCE-MRI参数、ADC差异,并分析DCE-MRI参数、ADC与ER、PR、Ki67、AR表达的相关性。结果经Spearman秩相关检验,发现ER、PR及AR阳性表达与直径、边缘毛刺呈显著负相关(P<0.05),AR表达阳性表达还与达峰时间(time to peak,TTP)、ADC值呈显著正相关(P<0.05);Ki67阳性表达与直径、边缘毛刺呈显著正相关(P<0.05),与TTP、ADC值呈显著负相关(P<0.05)。结论DCE-MRI形态学参数及TTP、ADC值与乳腺癌分子生物学标记物具有一定相关性,对判断乳腺癌预后有利。     

乳腺癌及前驱病变肿瘤分子标记物联合动态监测的研究与临床应用

目的：探讨乳腺癌及前驱病变肿瘤分子标记物联合动态监测的临床意义。方法：对100例乳腺癌、104例癌前病变（28例导管非典型增生ADH、31例低级别原位癌LG-DCIS、45例高级别原位癌HG-DCIS）患者采用化学发光法检测血清CA15-3、TPS、CA125的水平,化学显色法检测TSGF;ELISA法检测OPN分子标记物水平,并与30例正常乳腺组对照,结合ER、PR、c-erbB-2、Ki-67等临床病理因素统计分析。结果：与癌前病变组、正常乳腺对照组比较,乳腺浸润性导管癌分子标记物差异有统计学意义（P〈0．01）;与LG-DCIS、ADH及正常对照组比较,HG-DCIS血清CAl5-3、TSGF水平差异有统计学意义（P〈0．05）;LG-DCIS与ADH、正常对照组肿瘤标记物血清水平降低,但组间差异无统计学意义（P〉0．05）。血清肿瘤标记物水平与肿瘤大小（1cm为界）、患者年龄（50岁为界）、肿瘤部位、灶数（单灶、多灶）无关（P〉0．05）;与ER、PR、c-erbB-2、Ki-67差异相关,ER、PR阳性程度高,肿瘤标志物低负相关（P〈0．05）;c-erbB-2、Ki-67（20％为界）高则肿瘤标志物高正相关（P〈0．05）;淋巴结转移组与无转移组差异有统计学意义（P〈0．05）。与各单项检测相比,联合检测敏感性、准确性、阴性预测值明显提高,P〈0．05。结论：CA15-3、TPS、CA125、TSGF、OPN是乳腺导管癌诊断和监控转移的较好指标,对乳腺高级别粉刺型原位癌诊断和治疗、随访有-定价值,但对癌前病变诊断无特异性。     

Exosomes in esophageal cancer: A review on tumorigenesis,diagnosis and therapeutic potential

Exosomes are nanovesicles secreted from various types of cells and can be isolated from various bodily fluids, such as blood and urine. The number and molecular contents, including proteins and RNA of exosomes, have been shown to reflect their parental cell origins, characteristics and biological behaviors. An increasing number of studies have demonstrated that exosomes play a role in the course of tumorigenesis, diagnosis, treatment and prognosis, although its precise functions in tumors are still unclear. Moreover, owing to a lack of a standard approach, exosomes and its contents have not yet been put into clinical practice successfully. This review aims to summarize the current knowledge on exosomes and its contents in esophageal cancer as well as the current limitations/challenges in its clinical application, which may provide a basis for an all-around understanding of the implementation of exosomes and exosomal contents in the surveillance and therapy of esophageal cancer.     

食管癌患者Th1／Th2细胞因子检测的临床意义

目的　检测食管癌患者外周血CD3 T细胞分泌细胞因子的水平变化 ,分析Thl和Th2细胞的细胞因子免疫活动 ,为肿瘤的免疫治疗提供实验依据。方法　首先用刺激物刺激细胞 ,增加细胞内细胞因子的表达 ,然后加入荧光标记的特异性抗细胞因子单克隆抗体 ,特异性抗原抗体结合 ,最后应用流式细胞仪分析特异性细胞因子表达水平。同时用酶联免疫吸附法 (ELISA)检测相应的细胞因子。结果　食管癌患者Thl型细胞因子干扰素 -γ(IFN -γ)、白细胞介素 - 2 (IL - 2 )、白细胞介素 - 1 2 (IL - 1 2 )表达水平较正常对照组显著降低 ,Th2型细胞因子白细胞介素 - 4 (IL - 4 )和白细胞介素 - 1 0 (IL - 1 0 )表达水平较正常对照组升高 ,但差异无统计学意义。结论　食管癌患者Thl型反应模式处于弱势状态 ,相对地Th2型反应模式处于优势状态 ,Thl/Th2平衡失调 ,Thl/Th2平衡向Th2方向漂移。食管癌患者体内Th2型细胞因子模式占优势状态 ,这可能是肿瘤细胞发生免疫逃逸而避免被机体清除 ,从而导致肿瘤的发生或者转移的一种机制。     

基因nm23-H1和TGVβ1在人体食管癌中的表达及其临床病理关系的意义

目的探讨转移抑制基因nm23-H1及转化生长因子β1（TGFβ1）基因在人食管癌（EC）中的表达水平及其临床病理关系。方法应用免疫组化方法对56例人食管癌组织中转移抑制基因nm23～H1及TGFβ1基因表达蛋白水平进行研究。结果nm23-H1和TGFβ1表达水平与食管的TNM分期、细胞分化程度及食管癌的转移有密切关系（P〈0．05）。结论nm23-H1、TGFβ1基因表达水平同时降低，预示食管癌的转移和预后不良。     

食管癌及贲门癌手术方式探讨

食管癌及贲门癌手术方式较多。目前各级医院多不一致,合理的手术方式应尽可能彻底切除肿瘤及周围淋巴组织,手术安全简便及减少并发症的发生。我院自1985年8月~2005年8月共行723例食管癌及贲门癌手术。现将手术方式及并发症的相关性加以探讨报告如下。1资料与方法本组共723例,其     

PD-L1和PD-1在非小细胞肺癌中的表达及其临床意义

目的:探讨PD-L1和PD-1在非小细胞肺癌(NSCLC)中的表达及其与患者临床病理参数、预后的相关性。方法:收集47例NSCLC标本,运用免疫组化方法检测NSCLC中PD-L1和PD-1的表达,分析其与患者各项临床指标及预后的关系。结果:PD-L1在癌细胞及癌间质淋巴细胞和巨噬细胞的表达阳性率分别为48.93%(23/47)和61.70%(29/47),两者表达水平与肿瘤临床分期及淋巴结转移呈正相关(P<0.05),与患者预后呈负相关(P<0.05)。PD-1蛋白主要定位在癌间质淋巴细胞,PD-1+淋巴细胞数量与PD-L1蛋白在癌细胞及癌间质的表达均呈正相关(P<0.05)。结论:PD-L1与NSCLC分期、淋巴结转移、PD-1阳性淋巴细胞及预后密切相关。     

食管癌患者癌组织COX-2、VEGF-C表达水平对其预后生存的影响

目的分析食管癌患者癌组织环氧合酶2(COX-2)、血管内皮生长因子C(VEGF-C)表达水平对其预后生存的影响。方法回顾性分析2015年4月到2016年10月池州市人民医院经病理确诊的60例食管癌患者临床资料,采用免疫组织化学染色法检测其癌组织标本、癌旁正常食管黏膜组织标本中COX-2、VEGF-C蛋白表达水平,分析癌组织COX-2、VEGF-C表达水平的相关性,分析COX-2、VEGF-C表达水平与患者临床病理特征、预后生存的关系。结果食管癌组织标本中COX-2、VEGF-C表达阳性率均高于癌旁正常食管黏膜组织标本,差异有统计学意义(P<0.05);Spearman相关分析显示,食管癌患者癌组织COX-2表达阳性率与VEGF-C表达阳性率呈正相关(r=0.388,P<0.05);食管癌患者COX-2表达水平与性别、年龄、病理类型无关(P>0.05),而与分化程度、TNM分期、淋巴结转移有关(P<0.05),VEGF-C表达水平与性别、年龄、病理类型、TNM分期无关(P>0.05),而与分化程度、淋巴结转移有关(P<0.05);COX-2阳性患者12个月生存率低于COX-2阴性患者,VEGF-C阳性患者12个月生存率低于VEGF-C阴性患者,但差异无统计学意义(P>0.05);不同COX-2、VEGF-C表达水平患者12个月复发率比较,差异无统计学意义(P>0.05)。结论食管癌患者癌组织中COX-2、VEGF-C表达水平高,且其与临床病理参数也有一定关联,对预后生存的影响尚不明显,但临床检测COX-2、VEGF-C仍可为食管癌患者的预后评估提供参考。     

临床护理路径用于食管癌根治患者的效果观察

目的:探讨临床护理路径在食管癌根治术患者中的应用效果。方法:采用回顾性对照方法,将95例患者分为对照组(n=47)和实验组(n=48)。实验组实施临床护理路径,对照组采用常规整体护理。比较两组患者的住院时间、住院费用、并发症的发生情况及满意度等。结果:实验组患者的住院时间、卧床时间、胃管留置时间均明显低于对照组(P0.01),住院费用明显少于对照组(P0.01),并发症的发生情况低于对照组(P0.05),患者对护理工作的满意度高于对照组(P0.05)。结论:将临床护理路径应用于食管癌根治术患者中,可促进患者康复,提高护理质量和患者满意度,减轻患者负担。