Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinica
肝癌肿瘤切除术后患者应用肝动脉介入化疗栓塞术治疗的效果观察
肝癌肿瘤切除术后患者应用肝动脉介入化疗栓塞术治疗的效果观察作者：王义大来源：《现代养生·上半月》2024年第04期【摘要】目的探討肝癌肿瘤切除术后患者应用肝动脉介入化疗栓塞术（TACE）对血清肿瘤指标及预后的影响。
方法选取医院2019年1月- 2020年6月收治的76例原发性肝癌患者作为研究对象，在组间基线资料均衡的原则上，随机分为对照组和观察组，各38例。
所有患者均采用肝癌肿瘤切除术治疗，观察组在术后给予TACE治疗，比较治疗前及治疗8周后两组患者血清甲胎蛋白（AFP）、甲胎蛋白异质体L3（AFP-L3）、高尔基体蛋白-73（GP-73）变化及3年生存情况。
结果治疗前，两组患者血清AFP、AFP-L3及GP-73F表达水平比较差异无统计学意义（P>0.05）；治疗8周后，两组患者的AFP、AFP-L3及GP-73F表达水平均明显降低，但观察组患者的各项指标均低于对照组，差异有统计学意义（P<0.05）。
两组患者1年生存率比较差异无统计学意义（P>0.05）；观察组患者2年生存率（81.57%）、3年生存率（65.79%）均高于对照组（52.63%和39.47%），差异有统计学意义（P<0.05）。
结论 TACE 可显著降低肝癌肿瘤切除术患者血清AFP、AFP-L3及GP-73等肿瘤指标，提高近期生存率，临床疗效满意。
【关键词】肝动脉介入栓塞术；肝癌；肿瘤因子；预后中图分类号 R735.7 文献标识码 A 文章编号 1671-0223（2024）07--03Observation on the therapeutic effect of transcatheter arterial chemoembolization in patients with liver cancer after tumor resection Wang Yida. General Surgery Department 2， Linyi Cancer Hospital， Linyi 276000， China【Abstract】 Objective To explore the effect of transcatheter arterial chemoembolization （TACE） on serum tumor markers and prognosis in patients after liver cancer tumor resection. Methods A total of 76 patients with primary liver cancer admitted to the hospital from January 2019 to June 2020 were selected as the study subjects. Based on the principle of balanced baseline data between groups， they were randomly divided into a control group and an observation group， with 38 cases in each group. All patients were treated with liver cancer tumor resection， and the observation group received TACE treatment after surgery. The serum levels of alpha fetoprotein （AFP）， alpha fetoprotein heterogeneity L3 （AFP L3）， golgi apparatus protein-73 （GP-73）， and 3-year survival status of the two groups of patients were compared before and 8 weeks after treatment.Results Before treatment， there was no statistically significant difference in the expression levels of serum AFP， AFP-L3， and GP-73F between the two groups of patients（P>0.05）; After 8 weeks of treatment， the expression levels of AFP， AFP-L3， and GP-73F in both groups of patients were significantly reduced， but the various indicators of the observation group were lower than those of the control group， with statistical significance （P<0.05）. There was no statistically significant difference in 1-year survival rates between the two groups of patients （P>0.05）; The 2-year survival rate （81.57%） and 3-year survival rate （65.79%） of the observation group patients were higher than those of the control group （52.63% and 39.47%），and the difference was statistically significant （P<0.05）. Conclusion TACE can significantly reduce serum tumor markers such as AFP， AFP-L3， and GP-73 in patients undergoing liver cancer tumor resection， improve short-term survival rate， and achieve satisfactory clinical efficacy.【Key words】 Transcatheter arterial chemoembolization; Hepatocellular carcinoma; Tumor factors; Prognosis原发性肝癌是临床三大恶性肿瘤之一，肝癌肿瘤切除术是原发性肝癌患者的首选治疗手段，但由于该病早期无明显症状，多数患者确诊时已为中晚期，单纯手术治疗很难达到根治的效果，导致预后生存时间短，生存质量差。
胆汁酸谱在肺炎和肺癌鉴别诊断中的应用价值
文章编号：1673-8640（2021）01-001-07 中图分类号：R446.1 文献标志码：A DOI：10.3969/j.issn.1673-8640.2021.01.001胆汁酸谱在肺炎和肺癌鉴别诊断中的应用价值徐润灏1，邹 琛1，张 洁2，李 敏2，张舒林1（1.上海交通大学医学院，上海 200025；2.上海交通大学医学院附属仁济医院检验科，上海 200001）摘要：目的探讨肺癌患者血清胆汁酸谱的变化及其在肺炎与肺癌鉴别诊断中的价值。
方法 采用液相色谱-串联质谱法（LC-MS/MS）检测80例肺炎患者（肺炎组）、108例肺癌患者（肺癌组）和106名体检健康者（正常对照组）血清胆汁酸谱[5种游离胆汁酸，包括胆酸（CA）、鹅脱氧胆酸（CDCA）、脱氧胆酸（DCA）、石胆酸（LCA）、熊脱氧胆酸（UDCA）；10种结合胆汁酸，包括甘氨胆酸（GCA）、甘氨鹅脱氧胆酸（GCDCA）、甘氨脱氧胆酸（GDCA）、甘氨石胆酸（GLCA）、甘氨熊脱氧胆酸（GUDCA）、牛磺胆酸（TCA）、牛磺鹅脱氧胆酸（TCDCA）、牛磺脱氧胆酸（TDCA）、牛磺石胆酸（TLCA）、牛磺熊脱氧胆酸（TUDCA）]，同时检测血清总胆汁酸（TBA）及肿瘤标志物[糖类抗原（CA）125、CA19-9、癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA 21-1）、神经元特异性烯醇化酶（NSE）]。
采用二元Logistic回归分析筛选指标并建立诊断模型。
采用受试者工作特性（ROC）曲线分析各项指标及诊断模型鉴别诊断肺炎与肺癌的效能。
结果与正常对照组比较，肺炎组血清游离胆汁酸DCA、LCA、UDCA水平及结合胆汁酸GDCA、GLCA、TDCA、TLCA水平降低（P<0.01），血清结合胆汁酸GCDCA、TCDCA水平升高（P<0.01）；肺癌组血清游离胆汁酸CA、CDCA水平及结合胆汁酸GCDCA、TCDCA水平升高（P<0.01），血清结合胆汁酸TDCA、TLCA水平降低（P<0.01）。
卡瑞利珠单抗联合仑伐替尼或贝伐珠单抗治疗肝癌的疗效分析
研究论著卡瑞利珠单抗联合仑伐替尼或贝伐珠单抗治疗肝癌的疗效分析赖奉庭 刘华强 蔡永广【摘要】 目的 探讨卡瑞利珠单抗联合仑伐替尼或贝伐珠单抗治疗肝细胞癌（肝癌）的疗效差异。
方法 回顾性分析60例肝癌患者的资料，患者以不同治疗方法为A 组（卡瑞利珠单抗联合仑伐替尼）和B 组（卡瑞利珠单抗联合贝伐珠单抗）。
比较2组近期治疗效果及血清肿瘤标志物（甲胎蛋白、癌胚抗原、神经元特异性烯醇化酶、细胞角蛋白19片段）、基质金属蛋白酶-9（MMP -9）及血管内皮生长因子（VEGF ）水平，采用癌因性疲乏（CRF ）评估量表评价2组治疗前的CRF 程度，并比较2组治疗期间不良反应发生率、无进展生存情况和总生存情况。
结果 2组的近期治疗效果、不良反应发生率、无病生存情况和总生存情况比较差异均无统计学意义（P 均> 0.05）。
2组治疗后的血清肿瘤标志物、MMP -9、VEGF 水平和CRF 评分均比治疗前低，且B 组均比A 组低（P 均< 0.05）。
结论 卡瑞利珠单抗联合仑伐替尼或贝伐珠单抗治疗肝癌患者的疗效未发现明显差异，但卡瑞利珠单抗联合贝伐珠单抗治疗可以使患者的血清肿瘤标志物及MMP -9及VEGF 水平下降更明显，且可改善CRF 。
【关键词】 肝癌；卡瑞利珠；贝伐珠单抗；仑伐替尼；肿瘤标志物Clinical efficacy of camrelizumab combined with lunvatinib or bevacizumab in the treatment of hepatocellular carcinoma Lai Fengting ， Liu Huaqiang ， Cai Yongguang. Department of Medical Oncology ， Guangdong Medical University ，Guangdong Provincial Agricultural Reclamation Center Hospital ， Zhanjiang 524000， China Corresponding author ， Cai Yongguang ， E -mail:********************【Abstract 】Objective To evaluate the clinical efficacy of camrelizumab combined with lunvatinib or bevacizumab in the treatment of hepatocellular carcinoma （HCC ）. Methods Clinical data of 60 patients with HCC were retrospectively analyzed. All patients were divided into group A （camrelizumab combined with lunvatinib ） and group B （camrelizumab combined with bevacizumab ）. Short -term clinical efficacy and the expression levels of serum tumor markers （alpha -fetoprotein ， carcinoembryonic antigen ， neuron -specific enolase ， cytokeratin 19 fragment ）， matrix metalloproteinase -9 （MMP -9） and vascular endothelial growth factor （VEGF ） were compared between two groups. The degree of cancer -related fatigue （CRF ） before treatment was compared between two groups by using CRF scale. The incidence of adverse reactions ， progression -free survival （PFS ） and overall survival （OS ） during the treatment were analyzed between two groups. Results No significant differences were observed in the short -term clinical efficacy ， incidence of adverse reactions ， PFS and OS between two groups （all P > 0.05）. After treatment ， the expression levels of serum tumor markers ， MMP -9，VEGF and CRF scores in two group were significantly lower than those before treatment ， and the values in group B were lower than those in group A （all P < 0.05）. Conclusions No significant difference is observed in the clinical efficacy between camrelizumab combined with lunvatinib or bevacizumab in the treatment of HCC patients. However ， combined use of camrelizumab and bevacizumab can significantly lower the expression levels of serum tumor markers ， MMP -9 and VEGF and mitigate CRF in HCC patients.【Key words 】 Hepatocellular carcinoma ； Camrelizumab ； Bevaczumab ； Lunvatinib ； Tumor marker作者单位：524000 湛江，广东医科大学 广东省农垦中心医院肿瘤内科通信作者，蔡永广，E -mail:********************肝细胞癌（简称肝癌）是最常见的肝脏恶性肿瘤［1］。
雷替曲塞联合顺铂在原发性肝癌肝动脉化疗栓塞术中的应用价值分析
中外医疗 China &Foreign Medical Treatment 药物与临床雷替曲塞联合顺铂在原发性肝癌肝动脉化疗栓塞术中的应用价值分析王洪伟，安萃萃，刘超，海青山东省泰安市中心医院肿瘤微创科，山东泰安271000［摘要］目的分析原发性肝癌（primary liver cancer, PLC）肝动脉化疗栓塞术（transcatheter arterial chemoemboli‐zation, TACE）中雷替曲塞联合顺铂的应用价值。
方法回顾性分析入2021年1月—2022年12月于山东省泰安市中心医院确诊为PLC接受TACE治疗的62例患者的临床资料，对照组30例单独使用顺铂栓塞化疗，研究组32例选择雷替曲塞+顺铂栓塞化疗。
对比不同治疗方案对肝功能、血清肿瘤标志物的影响以及用药安全性及患者预后情况。
结果治疗后研究组疾病控制率高于对照组，总胆红素、谷丙转氨酶、甲胎蛋白、癌胚抗原水平均低于对照组，差异有统计学意义（P<0.05）。
研究组1年内存活率为87.50%，高于对照组的63.33%，差异有统计学意义（χ2=4.931，P<0.05）。
两组不良反应发生率对比，差异无统计学意义（P>0.05）。
结论 PLC接受雷替曲塞联合顺铂TACE治疗总体效果理想，不但能够一定程度改善肝功能，还能够提升肿瘤控制效果，延长患者存活期，用药安全性上有保障，值得推广运用。
［关键词］雷替曲塞；顺铂；原发性肝癌；肝动脉化疗栓塞；存活率［中图分类号］R246.5 ［文献标识码］A ［文章编号］1674-0742（2023）10(a)-0060-04Application Value of Raltitrexed Combined with Cisplatin in Transcath⁃eter Arterial Chemoembolization for Primary Liver CancerWANG Hongwei, AN Cuicui, LIU Chao, LI HaiqingDepartment of Minimally Invasive Oncology, Tai'an Central Hospital, Tai'an, Shandong Province, 271000 China[Abstract] Objective To analyze the application value of ratitrexed combined with cisplatin in transcatheter arterial chemoembolization (TACE) of primary liver cancer (PLC). Methods The clinical data of 62 patients diagnosed with PLC who received TACE treatment in Tai 'an Central Hospital of Shandong Province from January 2021 to December 2022 were retrospectively analyzed. 30 patients in the control group received cisplatin embolization chemotherapy alone, while 32 patients in the study group received ratitrexide plus cisplatin embolization chemotherapy. The effects of different treatment regimens on liver function, serum tumor markers, drug safety and patient prognosis were com‐pared. Results After treatment, the disease control rate of the study group was higher than that of the control group, and the levels of total bilirubin, alanine aminotransferase, A-fetoprotein and carcinoembryonic antigen were lower than those of the control group, the difference was statistically significant (P<0.05). The 1-year survival rate of the study group was 87.50%, higher than that of the control group (63.33%), and the difference was statistically significant (χ2=4.931, P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The overall effect of PLC treatment with ratitrexed combined with cisplatin TACE is ideal, which can not only improve liver function to a certain extent, but also improve tumor control effect, prolong pa‐tient survival, and guarantee drug safety, which is worthy of promotion and application.[Key words] Rhatitrexed; Cisplatin; Primary liver cancer; Transcatheter arterial chemoembolization; Survival rate DOI：10.16662/ki.1674-0742.2023.28.060[作者简介] 王洪伟（1983-），男，硕士，主治医师，研究方向为介入化疗。
血清肿瘤标志物诊断胃癌腹膜转移的临床价值
血清肿瘤标志物诊断胃癌腹膜转移的临床价值张慧卿;何波【摘要】目的探讨血清糖类抗原125(CA125)、癌胚抗原(CEA)和糖类抗原199(CA199)诊断胃癌腹膜转移的临床价值.方法胃癌晚期患者95例,其中发生腹膜转移32例,无腹膜转移63例.检测血清CA125、CEA和CA199水平,以血清CA125＞35 U/ml、CEA ＞2.5 ng/ml、CA199＞27 U/ml为阳性,并与病理组织和细胞学"金标准"进行比较.结果血清CA125、CEA和CA199阳性率分别为38.9%(37/95)、55.8%(53/95)和53.7%(51/95).CA125诊断腹膜转移的敏感性、特异性分别为90.6%(29/32)、87.3%(55/63),均明显优于CEA的25.0%(8/32)、28.6%(18/63)和CA199的37.5%(12/32)、38.1%(24/63).结论血清CA125可作为胃癌腹膜转移有效的预测和诊断指标.【期刊名称】《广西医学》【年(卷),期】2012(034)012【总页数】2页(P1672-1673)【关键词】胃癌;腹膜转移;糖类抗原125;诊断【作者】张慧卿;何波【作者单位】江西省肿瘤医院内三科,南昌市,330029;江西省肿瘤医院内三科,南昌市,330029【正文语种】中文【中图分类】R735.21981 年，Bast等［1］用卵巢浆液性乳突状囊腺癌细胞系OVCA433免疫小鼠，再与骨髓瘤杂交纯化得到一株单克隆抗体，命名为OC125，而对应的抗原命名为糖类抗原125(carbohydrate antigen 125，CA125)，也称为黏蛋白16(MUC16)。
多年来，CA125一直被视为卵巢癌相关抗原，在卵巢癌的诊治、监测等方面得到广泛应用。
有研究表明，CA125的表达与多种恶性肿瘤的发生、病理类型和转移方式存在密切关联［2-3］。
Fujimura等［4］对 12 例血清CA125≥35 U/ml的胃癌患者进行电子腹腔镜检查，结果12例患者均存在腹膜转移。
早期胃癌患者化疗前后血清AFP、CEA、CA19-9、CA125水平变化及其对淋巴结转移的预测价值
胃癌是临床常见恶性肿瘤之一，致死率高，死亡原因与癌症细胞的转移扩散密切相关[1]。
胃癌发病往往具有一定的隐匿性，早期没有症状或者症状不典型，常表现为乏力、食欲不振、腹痛腹胀等。
目前临床对于胃癌的治疗尚无明确有效的方法，常采取化疗为主、其他治疗为辅的治疗方式[2]。
血清肿瘤标志物包括血清甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原19-9 (CA19-9)、糖类抗原125(CA125)，是机体癌细胞产生的一种抗原和生物性活性物质，正常组织状态下含量甚微。
AFP是早期诊断原发性肝癌最敏感、最特异的指标，适用于大规模普查；CEA升高常见于大肠癌、胰腺癌、胃癌、乳腺癌等，在心血管疾病、糖尿病、结肠炎等疾病患者中常见CEA升高，常作为辅助指标[3-4]。
上皮性卵巢肿瘤患者中90%可见CA125升高，而血清CA19-9在胃癌患者中也明显升高，对临床诊断和治疗具有重要意义[5]。
本研究旨在观察早期胃癌患者化疗前后血清AFP、CEA、CA19-9、CA125表达水平，并探讨其对发生淋巴结转移的预测价值。
1资料与方法1.1一般资料回顾性分析2020年12月至2022年11月西安医学院附属宝鸡医院收治的56例早期胃癌患者的临床资料。
纳入标准：(1)经胃镜以及胃镜下的活检确诊为早期胃癌，均符合国际抗癌联盟TNM分期[6]中Ⅰ~Ⅱ期胃癌；(2)均首次确诊，预计生存期≥6个月；(3)无脏器功能障碍；(4)病例资料完整，化疗前后均有血清AFP、CEA、CA19-9、CA125等检测数据。
排除标准：(1)因胃癌并发症如出血、穿孔或梗阻等情况行急诊手术者；(2)具有严重的肝肺脏器疾病者；(3)胃间质瘤、胃肉瘤或胃淋巴瘤者；(4)资料不全者。
56例患者中男性44例，女性12例；年龄60~82岁，平均(69.38±10.26)岁；小胃癌16例，微小胃癌30例，点状癌10例。
通过腹部增强CT、肿瘤标志物检测和病理检查观察患者淋巴结转移情况，按患者是否有淋巴结转移分为转移组9例和未转移组47例。
肿瘤标志物tumormarkers
• 有效性(efficiency) 指该TM 能准确区分 肿瘤与非肿瘤患者的能力。 • 阳性似然比( positive likelihood ratio) 指该TM 真阳性率与假阳性率之比,反映 其正确判断阳性的可能性是错判阳性可 能性的倍数,越大越好 • 阴性似然比(negative likelihood ratio) 指该TM 假阴性率与真阴性率之比,反映 其错判阴性的可能性是正确判断阴性可 能性的倍数,越小越好
一、胚胎抗原
• 甲胎蛋白（α-Fetoprotein，AFP） • 癌胚抗原（carcinoembryonic antigen， CEA） • 癌胚铁蛋白 • 胰癌胚抗原 • β-癌胚抗原
（α-Fetoprotein， AFP）
甲胎蛋白
甲胎蛋白（α-Fetoprotein，
AFP）
• 糖蛋白，含590个氨基酸，分子量 70kD，半衰期在5天左右。 • 在胎儿发育到六周开始出现， 在 出生一周后消失。成人血清中含量 甚微。
癌胚抗原
癌胚抗原（carcinoembryonic antigen，CEA）
• 妊娠期2个月起存在于胎儿消化系统中， 如肠道、胰腺和肝脏中。 • 胎儿出生后其浓度明显下降。 • 在一些成人肿瘤组织，其中包括胚胎 性肿瘤，结肠、胃、肺、乳腺等癌组 织中可出现表达，并分泌于体液中。
CEA的相关归类
• CEA多肽，高度糖基化的大分子糖蛋白， 糖占60～70％。 • CEA相关多肽，包括36种糖蛋白。 • CEA家族，CEA多肽与CEA相关多肽组成 • CEA家族与免疫球蛋白超家族分子结构相 类似，因此CEA又可属免疫球蛋白超家族 中的一员。
• 细胞角蛋白是细胞体间的中间丝，存 在于所有的正常上皮细胞及上皮性癌 细胞中，在细胞中起支架作用，支撑 细胞及细胞核，根据其生化特性，可 分为20多种不同的类型。 • 作为标记物的细胞角蛋白主要是CK19
血清肿瘤标志物联合检测在肺癌诊断中的临床意义
血清肿瘤标志物联合检测在肺癌诊断中的临床意义李媛媛【期刊名称】《中国实用医药》【年(卷),期】2015(000)012【摘要】Objective To investigate the clinical application value of joint detection for serum tumor markers, such as carcino embryonie antigen (CEA), cytokeratins 19 fragment (CYFRA21-1), neuron specific enolase (NSE), and squamous cell carcinoma antigen (SCCA) for diagnosis of lung cancer.Methods There were 68 patients with lung cancer as the lung cancer group, and another 65 healthy people as the control group. Microparticle chemiluminescence was applied for content detection of CEA, CYFRA21-1, NSE, and SCCA. Comparisons were made on sensitivity, specificity and accuracy between single and joint detection of tumor markers.Results The lung cancer group had much higher contents of CEA, CYFRA21-1, NSE, and SCCA than the control group (P<0.05). The joint detection of 4 tumor markers had sensitivity as 81% and accuracy as 86%, which were all higher than those of single detection. The difference had statistical significance (P<0.05). <br> Conclusion Detection of serum CEA, CYFRA21-1, NSE, and SCCA has clinical application value in diagnosis of lung cancer. Joint detection can improve sensitivity and accuracy of diagnosis with good specificity and it is helpful for improving detection rate of lung cancer.%目的：探讨血清肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、鳞状细胞癌相关抗原(SCCA)联合检测在肺癌诊断中的临床应用价值。
血清肿瘤标志物检测在盆腔良恶性妇科肿瘤诊断与鉴别诊断中的意义
血清肿瘤标志物检测在盆腔良恶性妇科肿瘤诊断与鉴别诊断中的意义作者：吴杰儒来源：《中国当代医药》2017年第36期[摘要]目的探讨盆腔良恶性妇科肿瘤采取血清肿瘤标志物检测的诊断及鉴别意义。
方法选择2016年7月5日～12月23日在我院收治的盆腔妇科肿瘤患者50例作为研究对象，根据肿瘤性质分为良性组及恶性组（各25例），另取同期50例健康体检者为对照组。
所有患者均予以血清肿瘤标志物检测，观察检测阳性情况及生化指标含量。
结果恶性肿瘤组CA153、CA125阳性率分别为52.00%、92.00%，高于良性肿瘤组（4.00%、60.00%），差异有统计学意义（P0.05）；三组CEA、AFP检测阳性率比较，差异无统计学意义（P>0.05），恶性肿瘤组CA199、CA153、CA125分别为（150.89±7.06）、（107.57±4.24）、（446.19±10.07）U/ml，良性肿瘤组分别为（44.31±3.82）、（17.15±1.38）、（52.43±5.65）U/ml，均高于对照组 [（12.19±0.93）、（8.02±0.46）、（15.02±2.18）U/ml]，差异均有统计学意义（P[关键词]盆腔良恶性妇科肿瘤；诊断；血清肿瘤标志物检测[中图分类号] R473 [文献标识码] A [文章编号] 1674-4721（2017）12（c）-0123-03[Abstract]Objective To investigate the diagnosis and differential significance of serum tumor markers in pelvic benign and malignant gynecological tumors.Methods Fifty patients with pelvic gynecologic tumor in our hospital from July 5 to December 23，2016 were selected as the research object，According to the nature of the tumor was divided into benign and malignant group（25 cases），and 50 healthy subjects were taken as control group.All patients were given serum tumor markers to detect the detection of positive and biochemical indicators.Results The positive rate ofCA153，CA125 of malignant group were 52.00%，92.00%，higher than the benign group（4.00%，60.00%），the difference was statistically significant（P0.05）；CEA，AFP of the three groups had no statistical significance（P>0.05）.In the malignant groups，CA199，CA153，CA125，respectively were[（150.89±7.06），（107.57±4.24），（446.19±10.07）U/ml]，benign tumor group [（44.31±3.82），（17.15±1.38），（52.43±5.65）U/ml]，were higherthan[12.19±0.93），（8.02±0.46），（15.02±2.18）U/ml] of the control group，was statistically significant（P[Key words]Pelvic benign and malignant gynecological tumors；Diagnosis；Serum tumor markers detection妇科肿瘤严重危害着女性身心健康，作为常见疾病，可分为良性及恶性，良性肿瘤予以相应治疗即可痊愈[1-3]，但治疗不及时或不当，极有可能发展为恶性疾病，故确切可靠的诊断方法极为重要，早期鉴别良恶性肿瘤对于疾病发生发展意义重大。
安罗替尼联合白蛋白紫杉醇治疗晚期NSCLC的疗效及对血清肿瘤标志物的影响
2020年8月 第17卷 第16期药物与临床 Drugs and Clinic肺癌是一种最为常见的恶性肿瘤，其中非小细胞肺癌（Non-Small Cell Lung Cancer，NSCLC）约占80%［1］。
在NSCLC晚期临床中，常常存在着咳嗽、咯血、呼吸困难等症状，对患者生活质量造成极大不便，同时也会严重威胁着患者生命健康［2］。
目前，对于晚期NSCLC患者的治疗措施尚无统一方案，以往在临床治疗中，多采用铂类药物为基础的联合方案对患者进行救治，但如长期使用此类药物，会使患者耐药性增加，且易产生诸多不良反应，故笔者选取本院2018年5月—2020年5月诊治的65例晚期NSCLC患者进行对照观察，探讨安罗替尼+白蛋白紫杉醇治疗晚期NSCLC的疗效，现报告如下。
1 资料与方法1.1 一般资料选取本院2018年5月—2020年5月诊治的65例晚期NSCLC患者为观察对象。
随机将65例患者分为对照组30例和观察组35例。
观察组：男17例，女18例，平均年龄（56.87±3.24）岁，其中鳞癌12例、腺癌14例、其他9例；对照组：男14例，女16例，平均年龄（56.24±3.47）岁，其中鳞癌11例、腺癌12例、其他7例。
两组患者一般资料比较，差异无统计学意义（P＞0.05），存在可比性。
1.2 纳入与排除标准纳入标准：（1）经临床病理确诊为晚期NSCLC，且经过三线及以上治疗；（2）年龄50～65岁；（3）经患者及家属同意，且通过医院伦理委员会审查。
排除标准：（1）其他肿瘤疾安罗替尼联合白蛋白紫杉醇治疗晚期NSCLC的疗效及对血清肿瘤标志物的影响代翠莲，王双英兰考县中心医院，河南开封 471000［摘要］目的：探讨安罗替尼联合白蛋白紫杉醇治疗晚期非小细胞肺癌（NSCLC）的疗效及对血清肿瘤标志物（TM）的影响。
方法：以随机抛硬币方式将本院2018年5月—2020年5月诊治的65例晚期NSCLC患者分为对照组（n=30）和观察组（n=35），分别进行白蛋白紫杉醇和安罗替尼+白蛋白紫杉醇治疗。
屠呦呦介绍 英语作文开头
屠呦呦介绍英语作文开头As an accomplished scientist and Nobel laureate, Tu Youyou has made significant contributions to the field of medicine through her groundbreaking research on traditional Chinese medicine. Born in 1930 in Ningbo, Zhejiang province, Tu Youyou's interest in medicine was sparked at a young age by her father, who was a practitioner of traditional Chinese medicine. This early exposure to the healing properties of traditional herbs and remedies laid the foundation for Tu Youyou's future work in the field of pharmacology.Tu Youyou's most notable achievement came in the 1970s when she led a team of researchers in the discovery of artemisinin, a compound derived from the sweet wormwood plant, that proved to be highly effective in treating malaria. This breakthrough in the treatment of malaria earned Tu Youyou the Nobel Prize in Physiology or Medicinein 2015, making her the first Chinese woman to receive thisprestigious award.In addition to her work on artemisinin, Tu Youyou has also conducted extensive research on other traditional Chinese medicines, seeking to identify new compounds with potential therapeutic benefits. Her dedication to bridging the gap between traditional Chinese medicine and modern pharmacology has paved the way for new discoveries and advancements in the field of medicine.Tu Youyou's research has not only had a profound impact on the treatment of malaria but has also inspired a new generation of scientists to explore the potential of traditional Chinese medicine. Her commitment to scientific inquiry and her tireless efforts to improve global health have earned her recognition and respect from the international scientific community.In conclusion, Tu Youyou's groundbreaking research on traditional Chinese medicine has revolutionized the field of pharmacology and has saved countless lives around theworld. Her dedication, perseverance, and innovativethinking serve as an inspiration to all who strive to makea positive impact on the world through scientific discovery.。
219444018_卡铂和紫杉醇化疗联合放疗治疗高危子宫内膜癌患者的效果及对血清炎症因子和肿瘤标志物
*基金项目：南充市市校科技战略合作项目（22SXQT0238）①川北医学院附属医院 四川 南充 637000卡铂和紫杉醇化疗联合放疗治疗高危子宫内膜癌患者的效果及对血清炎症因子和肿瘤标志物的影响*杨凡① 谌伦华① 张娟① 鲜标① 张燕萍① 翟靓鑫①【摘要】 目的：探究分析卡铂和紫杉醇化疗联合放疗治疗高危子宫内膜癌的临床效果。
方法：选取2020年6月—2022年6月川北医学院附属医院收治的100例高危子宫内膜癌患者为研究对象，通过患者就诊病历号抽签的方法将其平均划分为研究组、对照组，各50例。
对照组采用调强放疗，研究组采用卡铂和紫杉醇化疗联合调强放疗。
比较两组疾病控制率、疾病缓解率、血清肿瘤标志物[血清甲壳质酶蛋白40（YKL-40）、人附睾蛋白4（HE4）、催乳素（PRL）]、炎症因子[白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）]、生活质量及不良反应发生情况。
结果：对比两组治疗后疾病控制率、疾病缓解率，研究组均高于对照组，差异有统计学意义（P <0.05）。
研究组患者治疗后肿瘤标志物水平（YKL-40、HE4、PRL）均低于对照组，差异有统计学意义（P <0.05）。
对比两组治疗后血清炎症因子（IL-6、IL-8、TNF-α）水平，研究组均低于对照组，差异有统计学意义（P <0.05）。
对比两组治疗后各项生活质量评分，研究组均高于对照组，差异有统计学意义（P <0.05）。
对比两组不良反应发生率，差异无统计学意义（P >0.05）。
结论：卡铂和紫杉醇化疗与放疗联合应用于高危子宫内膜癌患者治疗干预中可有效控制病情，提高疾病缓解效果，经血清学检测患者肿瘤标志物及炎症因子水平均降低，生活质量显著提高。
【关键词】 卡铂 紫杉醇 放疗 高危子宫内膜癌 doi：10.14033/ki.cfmr.2023.15.001 文献标识码 A 文章编号 1674-6805（2023）15-0001-05 Effect of Carboplatin and Paclitaxel Chemotherapy Combined with Radiotherapy in the Treatment of High-risk Endometrial Cancer and Its Influence on Serum Inflammatory Factors and Tumor Markers/YANG Fan, SHEN Lunhua, ZHANG Juan, XIAN Biao, ZHANG Yanping, ZHAI Liangxin. //Chinese and Foreign Medical Research, 2023, 21(15): 1-5 [Abstract] Objective: To investigate and analyze the clinical efficacy of Carboplatin and Paclitaxel chemotherapy combined with radiotherapy in the treatment of high-risk endometrial cancer. Method: A total of 100 patients with high-risk endometrial cancer admitted to the Affiliated Hospital of North Sichuan Medical College from June 2020 to June 2022 were selected as the study objects, they were evenly divided into study group and control group by medical record number lottery, with 50 cases in each group. The control group received intensity modulated radiotherapy, and the study group received Carboplatin and Paclitaxel chemotherapy combined intensity modulated radiotherapy. Disease control rate, disease remission rate, serum tumor markers [serum chitinase protein 40 (YKL-40), human epididymal protein 4 (HE4), prolactin (PRL)], inflammatory factors [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] and quality of life and occurrence of adverse reactions between the two groups were compared. Result: Compared with the disease control rate and remission rate of the two groups after treatment, those in the study group were higher than those in the control group, the differences were statistically significant (P <0.05). The levels of tumor markers (YKL-40, HE4, PRL) in the study group were lower than those in the control group after treatment, the differences were statistically significant (P <0.05). The levels of serum inflammatory cytokines (IL-6, IL-8, TNF-α) were compared between the two groups after treatment, those in the study group were lower than those in the control group, the differences were statistically significant (P <0.05). Compared with all dimension quality of life scores in the two groups after treatment, those in the study group were higher than those in the control group, the differences were statistically significant (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion: Carboplatin and Paclitaxel chemotherapy combined with radiotherapy have significant effect on high-risk endometrial cancer patients, which can reduce the level of serum inflammatory factors and tumor markers, improve the quality of life of patients. [Key words] Carboplatin Paclitaxel Radiotherapy High-risk endometrial cancer First-author's address: Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China 资料数据统计显示，子宫内膜癌发病率仅低于子宫颈癌与乳腺癌，致病原因包括卵巢疾病、不孕、绝经时间过晚、肥胖、糖尿病等[1]。
结肠镜及活检联合血清肿瘤标志物、CT在结肠高级别上皮内瘤变及早期癌变的诊断价值
结肠镜及活检联合血清肿瘤标志物、CT在结肠高级别上皮内瘤变及早期癌变的诊断价值作者：***来源：《中国现代医生》2022年第08期[摘要] 目的探討结肠镜活检、血清肿瘤标志物、CT对高级别结直肠上皮内瘤变及早期癌变的诊断价值。
方法对本院145例结直肠癌患者进行前瞻性研究，其中包括80例结直肠癌和65例高级别上皮内瘤变。
所有患者术前均行肿瘤标志物CA199、CA724、癌胚抗原、多层螺旋CT及结肠镜活检。
结果结直肠癌组CA199、CA724、癌胚抗原、CT及肿瘤大小值均高于高级别结直肠上皮内瘤变组（P[关键词] 结肠镜活检;血清肿瘤标志物;CT;高级别结直肠上皮内瘤变;结直肠癌;诊断价值[中图分类号] R574.2 [文献标识码] B [文章编号] 1673-9701（2022）08-0024-05The value of colonoscopy biopsy， serum tumor markers， and CT in the diagnosis of colorectal polyps and early carcinogenesisZHOU DanDepartment of Gastroenterology， Hangzhou Xixi Hospital，Hangzhou 310023，China[Abstract] Objective To inexplore the diagnostic value of colonoscopy biopsy， serum tumor markers， and CT for high-grade intraepithelial neoplasia and early canceration of colorectal polyps. Methods A total of 145 patients with colorectal polyps in Hangzhou Xixi Hospital were prospectively studied， including 80 cases of colorectal cancer and 65 cases of high-grade intraepithelial neoplasia. All patients underwent tumor markers （CA199， CA724， carcinoembryonic antigen）， CT，and colonoscopy biopsy before surgery. Results The values of CA199， CA724， carcinoembryonic antigen， CT， and tumor size in the colorectal cancer group were higher than those in the high-grade intraepithelial neoplasia group （P[Key words] Colonoscopy biopsy; Serum tumor markers; CT; Colorectal polyps; Colorectal cancer; Diagnostic value结直肠癌是最常见的消化系统恶性疾病。
210975562_纳武利尤单抗联合含铂方案化疗治疗晚期三阴性乳腺癌对血清肿瘤标志物的影响及3年生存
纳武利尤单抗联合含铂方案化疗治疗晚期三阴性乳腺癌对血清肿瘤标志物的影响及3年生存率观察郭宏果，刘军，程才，乔松，陆婉玲空军第九八六医院肿瘤血液科，陕西西安710054【摘要】目的探讨纳武利尤单抗联合含铂方案化疗治疗晚期三阴性乳腺癌(TNBC)对患者血清肿瘤标志物的影响，并观察其3年生存率。
方法回顾性分析2015年1月至2018年5月期间空军第九八六医院收治的68例晚期TNBC 患者的临床资料，根据治疗方法分组，其中34例采用含铂方案化疗治疗者纳入对照组，34例在对照组治疗的基础上联合纳武利尤单抗治疗者纳入观察组，两组患者均连续治疗4个周期(21d 为一个治疗周期)，治疗后随访3年。
比较两组患者治疗后的临床疗效、治疗前及治疗后的血清肿瘤标志物水平[糖类抗原153(CA153)、特异性组织多肽抗原(TPS)、胸苷激酶1(TK1)]、3年生存率及治疗期间的毒副反应。
结果治疗后，观察组患者的客观缓解率为44.12%，明显高于对照组的20.59%，差异具有统计学意义(P <0.05)；治疗后，观察组患者的血清CA153、TPS 、TK1水平分别为(20.58±4.15)U/mL 、(5.60±1.66)ng/mL 、(1.50±0.31)pmol/L ，明显低于对照组的(24.42±4.63)U/mL 、(7.16±2.03)ng/mL 、(1.89±0.37)pmol/L ，差异均有统计学意义(P <0.05)；经生存曲线分析结果显示，观察组患者的3年生存率为47.06%，明显高于对照组的20.59%，差异有统计学意义(P <0.05)；观察组患者治疗期间的天冬氨酸转氨酶升高、丙氨酸转氨酶升高发生率高于对照组，差异均具有统计学意义(P <0.05)；两组患者治疗期间的食欲减退、疲劳、肌肉骨骼痛、消化道反应、贫血、呼吸困难、四肢水肿、血小板减少、中性粒细胞减少等毒副反应比较差异均无统计学意义(P >0.05)。
鼻咽癌患者血清细胞角蛋白19片段检测的临床价值
鼻咽癌患者血清细胞角蛋白19片段检测的临床价值刘玉;王朱健;曹文俊;宋新貌;王胜资【摘要】目的探讨血清细胞角蛋白19片段(CYFRA21-1)作为鼻咽癌(NPC)诊断及治疗预后标志物的临床价值.方法收集2013年7月～2016年7月在本院就诊的NPC患者336例,收集年龄、性别匹配的健康体检人群208例作为健康对照组.同时在纳入的NPC患者中随机随访100例,于治疗前及治疗后3个月各收集外周血1次,其中10例分别在放疗前及放疗5、10、15、20、25、30次时收集外周血.采用电化学发光法检测血清中的CYFRA21-1.结果 NPC患者血清CYFRA21-1水平为(4.12 ±3.23) ng／mL,显著高于健康对照组的(2.15 ±0.94)ng／mL(t＝10.507, P＜0.001). CYFRA21-1的受试者工作特征曲线(ROC曲线)诊断NPC的曲线下面积为0.765(最佳临界值为2.61,灵敏度为63.10%,特异度为79.33%, P＜0.001). NPC患者治疗后血清CYFRA21-1水平为(2.93 ±3.61)ng／mL,明显低于治疗前的(4.10 ±3.83)ng／mL(P＝0.020 3),并随放疗次数的增加而呈下降趋势.结论血清CYFRA21-1可作为NPC诊断和疗效监测的有效参考指标.%Objective To evaluate the clinical values of serum cytokeratin-19 fragment (CYFRA21-1) for the diagnosis and prognosis of nasopharyngeal carcinoma( NPC).Methods Electrochemiluminescence immunoassay was used to measure the serum CYFRA21-1 in untreated patients with NPC (n＝336) and in the age and sex-matched healthy control group (n＝208).One hundred NPC patients were randomly chosen and followed up, whose blood was collected before and 3 months after the treatment.Among them, the blood of 10 cases were collected before the treatment and after the5th,10th,15th, 20th,25th and 30th radiotherapy.Results Compared with thehealthy controls (2.15 ± 0.94 ng／mL), the level of serum CYFRA21-1 in the patients with NPC (4.12 ±3.23 ng／mL) was significantly elevated (t＝10.507, P＜0.001).The area of receiver operating characteristic curve (ROC curve) was 0.765(best cut-off value was 2.61, sensitivity was 63.10%, specitivity was 79.33%, P＜0.001).The level of serum CYFRA21-1 after the treatment (2.93 ±3.61ng／mL) was significantly lower than that before treatment (4.10 ±3.83 ng／mL, P＝0.020 3). And the level of serum CYFRA21-1 was in a downtrend with the increasing numbers of radiotherapies.Conclusions The level of serum CYFRA21-1 is an effective reference for the diagnosis and treatment of NPC.【期刊名称】《中国眼耳鼻喉科杂志》【年(卷),期】2018(018)002【总页数】3页(P112-114)【关键词】鼻咽癌;血清细胞角蛋白19片段;血清【作者】刘玉;王朱健;曹文俊;宋新貌;王胜资【作者单位】复旦大学附属眼耳鼻喉科医院检验科上海 200031;复旦大学附属眼耳鼻喉科医院检验科上海 200031;复旦大学附属眼耳鼻喉科医院检验科上海200031;复旦大学附属眼耳鼻喉科医院放疗科上海 200031;复旦大学附属眼耳鼻喉科医院放疗科上海 200031【正文语种】中文全世界约80%的鼻咽癌(nasopharyngeal carcinoma, NPC)患者在中国，华南地区发病率可达(20～30)/10万[1-3]。
211003633_血常规炎症指标联合血清肿瘤标志物在肺癌诊断中的价值分析
㊃857㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6㊃论著㊃D O I:10.3969/j.i s s n.1672-9455.2023.06.010血常规炎症指标联合血清肿瘤标志物在肺癌诊断中的价值分析*谢惠杰1,邹红1,吴赓2,杨蓉3,黄慧芳4ә1.福建医科大学附属协和医院检验科,福建福州350001;2.福建医科大学医学技术与工程学院,福建福州350001;3.福建医科大学附属协和医院医务部信息随访中心,福建福州350001;4.福建医科大学附属协和医院中心实验室,福建福州350001摘要:目的从血常规炎症指标和血清肿瘤标志物中寻找能诊断肺癌的血液学指标组合㊂方法收集2018年1月至2021年4月在福建医科大学附属协和医院就诊的289例肺癌患者(肺癌组)㊁93例肺良性病变患者(肺良性病变组)和89例健康体检人员(体检组)的血液检验数据,包括血小板计数(P L T)㊁血小板分布宽度(P DW)㊁平均血小板体积(M P V)㊁血小板压积(P C T)㊁粒细胞绝对值(N e u#)㊁粒细胞百分比(N e u%)㊁淋巴细胞绝对值(L y m#)㊁淋巴细胞百分比(L y m%)㊁中性粒细胞与淋巴细胞比值(N L R)㊁红细胞体积分布宽度变异系数(R DW-C V)和红细胞体积分布宽度标准差(R DW-S D)等血常规炎症指标,癌胚抗原(C E A)㊁糖类抗原19-9 (C A19-9)㊁甲胎蛋白(A F P)㊁细胞角蛋白19的可溶性片段(C Y F R A)㊁神经元特异性烯醇化酶(N S E)㊁胃泌素释放肽前体(p r o-G R P)㊁总前列腺特异性抗原(t P S A)㊁游离前列腺特异性抗原(f P S A)和C A125等血清肿瘤标志物,以及乳酸脱氢酶(L D H)㊂采用秩和检验比较这些指标在3组间的差异,选取组间差异有统计学意义的指标用于下一步的R O C曲线诊断分析,再选择曲线下面积(A U C)较大的指标用于进一步的联合诊断分析,最后应用二分类L o g i s t i c回归联合R O C曲线综合分析不同指标联合模式对肺癌的诊断能力㊂结果(1)P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A㊁C Y F R A在3组间的水平差异均有统计学意义(P< 0.05)㊂(2)R O C曲线分析P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A㊁C Y F R A对肺癌的诊断效能,结果显示仅P C T㊁R DW-C V㊁C Y F R A㊁L D H诊断肺癌的A U C>0.6,分别为0.626㊁0.603㊁0.707㊁0.630㊂(3)将P C T㊁R DW-C V㊁C Y F R A㊁L D H相互联合,进行二分类L o g i s t i c回归和R O C曲线综合分析,结果显示,各种联合模式中,R DW-C V+L D H+C Y F R A诊断肺癌的A U C最大,为0.823,而P C T+R DW-C V+ L D H+C Y F R A诊断肺癌的A U C为0.821,P C T+R DW-C V诊断肺癌的特异度最高(92.0%);P C T+R DW-C V+L D H+C Y F R A诊断肺癌的灵敏度最高(76.5%)㊂结论在所检测的血液指标中,诊断肺癌效能最高的单项指标为C Y F R A,C Y F R A与R DW-C V㊁P C T㊁L D H中的一项或多项联合诊断肺癌的效能优于单项指标,其中R DW-C V+L D H+C Y F R A及P C T+R DW-C V+L D H+C Y F R A模式的诊断效能较大㊂关键词:肺癌;血常规炎症指标;肿瘤标志物中图法分类号:R734.2;R446.1文献标志码:A文章编号:1672-9455(2023)06-0758-06A n a l y s i s o n v a l u e o f b l o o d r o u t i n e i n f l a m m a t o r y i n d e x e s c o m b i n e dw i t h s e r u m t u m o r m a r k e r s i n d i a g n o s i s o f l u n g c a n c e r*X I E H u i j i e1,Z O U H o n g1,WU G e n g2,Y A N G R o n g3,HU A N G H u i f a n g4ә1.D e p a r t m e n t o f C l i n i c a l L a b o r a t o r y,A f f i l i a t e d U n i o n H o s p i t a l,F u j i a n M e d i c a l U n i v e r s i t y,F u z h o u,F u j i a n350001,C h i n a;2.S c h o o l o f M e d i c a l T e c h n o l o g y a n d E n g i n e e r i n g,F u j i a n M e d i c a l U n i v e r s i t y, F u z h o u,F u j i a n350001,C h i n a;3.I n f o r m a t i o n F o l l o w-u p C e n t e r,D e p a r t m e n t o f M e d i c a l A f f a i r s, A f f i l i a t e d U n i o n H o s p i t a l,F u j i a n M e d i c a l U n i v e r s i t y,F u z h o u,F u j i a n350001;4.C e n t r a l L a b o r a t o r y,A f f i l i a t e d U n i o n H o s p i t a l,F u j i a n M e d i c a l U n i v e r s i t y,F u z h o u,F u j i a n350001,C h i n aA b s t r a c t:O b j e c t i v e T o s e e k t h e h e m a t o l o g i c a l i n d e x e s c o m b i n a t i o n f r o m t h e b l o o d r o u t i n e i n f l a mm a t o r y i n d e x e s a n d s e r u m t u m o r m a r k e r s f o r d i a g n o s i n g l u n g c a n c e r.M e t h o d s T h e b l o o d t e s t d a t a o f289p a t i e n t s w i t h l u n g c a n c e r(l u n g c a n c e r g r o u p),93p a t i e n t s w i t h l u n g b e n i g n d i s e a s e(l u n g b e n i g n d i s e a s e g r o u p)a n d89 h e a l t h y s u b j e c t s u n d e r g o i n g t h e p h y s i c a l e x a m i n a t i o n(p h y s i c a l e x a m i n a t i o n g r o u p)i n t h e A f f i l i a t e d U n i o n*基金项目:福建省高水平实验研究平台建设项目[闽201704]㊂作者简介:谢惠杰,男,技师,主要从事血液分子检验相关研究㊂ә通信作者,E-m a i l:h u a n g h u i f@126.c o m㊂网络首发h t t p s://k n s.c n k i.n e t/k c m s/d e t a i l//50.1167.R.20230203.1135.002.h t m l(2023-02-03)Copyright©博看网. All Rights Reserved.H o s p i t a l o f F u j i a n M e d i c a l U n i v e r s i t y f r o m J a n u a r y2018t o A p r i l2021w e r e c o l l e c t e d,i n c l u d i n g t h e b l o o d r o u t i n e i n f l a mm a t o r y i n d i c a t o r s s u c h a s p l a t e l e t c o u n t(P L T),p l a t e l e t d i s t r i b u t i o n w i d t h(P DW),m e a n p l a t e-l e t v o l u m e(M P V),p l a t e l e t h e m a t o c r i t(P C T),a b s o l u t e v a l u e o f g r a n u l o c y t e(N e u#),p e r c e n t a g e o f g r a n u l o-c y t e s(N e u%),a b s o l u t e v a l u e o f l y m p h o c y t e s(L y m#),p e r c e n t a g e o f l y m p h o c y t e s(L y m%),n e u t r o p h i l s t o l y m p h o c y t e s r a t i o(N L R),c o e f f i c i e n t o f v a r i a t i o n o f r e d b l o o d c e l l v o l u m e d i s t r i b u t i o n w i d t h(R DW-C V), s t a n d a r d d e v i a t i o n o f r e d b l o o d c e l l v o l u m e d i s t r i b u t i o n w i d t h(R DW-S D),s e r u m t u m o r m a r k e r s s u c h a s c a r c i-n o e m b r y o n i c a n t i g e n(C E A),c a r b o h y d r a t e a n t i g e n19-9(C A19-9),a l p h a-f e t o p r o t e i n(A F P),s o l u b l e f r a g m e n t o f c y t o k e r a t i n19(C Y F R A),n e u r o n-s p e c i f i c e n o l a s e(N S E),g a s t r i n-r e l e a s i n g p e p t i d e p r e c u r s o r(p r o-G R P), t o t a l p r o s t a t e s p e c i f i c a n t i g e n(t P S A),f r e e p r o s t a t e s p e c i f i c a n t i g e n(f P S A),C A125a s w e l l a s l a c t a t e d e h y d r o-g e n a s e(L D H).T h e r a n k s u m t e s t w a s u s e d t o c o m p a r e t h e d i f f e r e n c e s o f t h e s e i n d i c a t o r s a m o n g t h e t h r e e g r o u p s.T h e i n d i c a t o r s w i t h s t a t i s t i c a l l y s i g n i f i c a n c e b e t w e e n t h e g r o u p s w e r e s e l e c t e d f o r t h e d i a g n o s i s a n d a-n a l y s i s o f R O C c u r v e o f t h e n e x t s t e p,a n d t h e i n d i c a t o r s w i t h l a r g e r a r e a u n d e r t h e c u r v e(A U C)w e r e s e l e c t-e d f o r c o n d u c t i n g t h e f u r t h e r j o i n t d i a g n o s t i c a n a l y s i s.F i n a l l y,t h e b i n a r y c l a s s i f i c a t i o n L o g i s t i c r e g r e s s i o n c o m b i n e d w i t h R O C c u r v e w e r e u s e d t o c o m p r e h e n s i v e l y a n a l y z e t h e d i a g n o s t i c a b i l i t y o f d i f f e r e n t i n d i c a t o r s c o m b i n e d m o d e f o r l u n g c a n c e r.R e s u l t s(1)P L T,M P V,P C T,L y m#,R DW-C V,R DW-S D,L D H,N e u%, C E A a n d C Y F R A h a d s t a t i t i c a l l y s i g n i f i c a n t d i f f e r e n c e s a m o n g t h e t h r e e g r o u p s(P<0.05).(2)T h e R O C c u r v e w a s u s e d t o a n a l y z e t h e d i a g n o s t i c e f f i c i e n c y o f P L T,M P V,P C T,L y m#,R DW-C V,R DW-S D,L D H, N e u%,C E A,a n d C Y F R A f o r l u n g c a n c e r.T h e r e s u l t s s h o w e d t h a t o n l y P C T,R DW-C V,C Y F R A,a n d L D H f o r d i a g n o s i n g l u n g c a n c e r h a d A U C>0.6,w h i c h w e r e0.626,0.603,0.707a n d0.630,r e s p e c t i v e l y.(3)T h e m u t u a l c o m b i n a t i o n o f P C T,R DW-C V,C Y F R A a n d L D H w a s c a r r i e d o u t f o r c o n d u c t i n g t h e c o m p r e h e n s i v e a-n a l y s i s o f b i n a r y l o g i s t i c r e g r e s s i o n a n d R O C c u r v e.T h e r e s u l t s s h o w e d t h a t a m o n g t h e v a r i o u s c o m b i n a t i o n m o d e s,A U C o f R DW-C V+L D H+C Y F R A i n d i a g n o s i n g l u n g c a n c e r w a s t h e l a r g e s t,w h i c h w a s0.823,w h i l e A U C o f P C T+R DW-C V+L D H+C Y F R A i n d i a g n o s i n g l u n g c a n c e r w a s0.821,a n d t h e s p e c i f i c i t y o f P C T+ R DW-C V i n d i a g n o s i n g l u n g c a n c e r w a s t h e h i g h e s t(92.0%);t h e s e n s i t i v i t y o f P C T+R DW-C V+L D H+C Y-F R A i n d i a g n o s i n g l u n g c a n c e r w a s t h e h i g h e s t(76.5%).C o n c l u s i o n A m o n g t h e d e t e c t e d b l o o d i n d i c a t o r s, t h e s i n g l e i n d i c a t o r w i t h t h e h i g h e s t d i a g n o s t i c e f f i c a c y f o r l u n g c a n c e r i s C Y F R A.T h e c o m b i n e d d i a g n o s t i c e f f i c a c y o f C Y F R A a n d o n e o r m o r e o f R DW-C V,P C T,a n d L D H i n l u n g c a n c e r i s s u p e r i o r t o t h e s i n g l e i n d i-c a t o r,w i t h R DW-C V+L D H+C Y F R A a n d P C T+R DW-C V+L D H+C Y F R A m o d e s h a v i n g g r e a t e r d i a g n o s-t i c e f f i c a c y.K e y w o r d s:l u n g c a n c e r;b l o o d r o u t i n e i n f l a mm a t o r y m a r k e r s;t u m o r m a r k e r s肺癌是癌症患者死亡的首要原因[1]㊂现阶段肺癌的诊断多是在出现疑似症状后结合影像学手段,对病变部位进行活检㊂但病理活检对患者创伤大,且诊断周期长,因此,利用简单易行㊁可反复取样检测的血液检验指标建立肺癌的诊断模型具有较好的临床价值与应用前景㊂肿瘤标志物在部分早期肺癌患者血清中会升高,但并不特异,在部分肺部良性病变中也会异常升高,因此,在肺癌诊断中的特异度与灵敏度有限,需结合其他指标以提高诊断效能㊂癌症与炎症密切相关[2]㊂血常规中的炎症指标有血小板计数(P L T)㊁血小板压积(P C T)㊁平均血小板体积(M P V)㊁血小板分布宽度(P DW)㊁粒细胞绝对值(N e u#)㊁粒细胞百分比(N e u%)㊁淋巴细胞绝对值(L y m#)㊁淋巴细胞百分比(L y m%)与红细胞分布宽度(R DW)等㊂乳酸脱氢酶(L D H)可反映肿瘤细胞代谢状态,有助于临床肿瘤的早期诊断[3]㊂因此,本文拟结合血清肿瘤标志物㊁血常规炎症指标和L D H等常规血液检测指标,初步探讨肺癌诊断的常规检验指标联合应用方案㊂1资料与方法1.1一般资料收集2018年1月至2021年4月在福建医科大学附属协和医院初次就诊㊁经组织病理学确诊㊁未进行放化疗或肺部手术等治疗的肺癌患者289例作为肺癌组;同期被确诊为肺炎㊁肺部良性结节㊁慢性阻塞性肺疾病(C O P D)等肺部良性病变的患者93例作为肺良性病变组;来自体检中心的健康体检者89例作为体检组㊂排除标准:其他恶性肿瘤(除外肺癌);急慢性炎症(除外肺炎);对血常规㊁血清肿瘤标志物以及L D H指标有影响的疾病,如血液系统疾病㊁术前急性损伤及肝㊁肾等器官器质性病变等㊂本研究经福建医科大学附属协和医院伦理委员会批准(2020K Y053)㊂肺癌组中男123例(42.6%)㊁女㊃957㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6Copyright©博看网. All Rights Reserved.166例(57.4%),年龄52(44,61)岁,小细胞型肺癌16例(5.5%)㊁肺腺癌245例(84.8%)㊁肺鳞状细胞癌18例(6.2%)㊁其他10例(3.5%)㊂肺良性病变组中男57例(61.3%)㊁女36例(38.7%),年龄51(45,62)岁,肺部感染41例(44.1%)㊁C O P D4例(4.3%)㊁肺部良性结节11例(11.8%)㊁其他37例(39.8%)㊂体检组中男46例(51.7%)㊁女43例(48.3%),年龄48 (39,58)岁㊂性别构成在肺癌组与肺良性病变组间差异有统计学意义(P<0.05),年龄构成在3组间差异无统计学意义(P>0.05)㊂1.2研究方法收集所有研究对象的血液检验数据,包括P L T㊁P DW㊁M P V㊁P C T㊁N e u#㊁N e u%㊁L y m #㊁L y m%㊁中性粒细胞与淋巴细胞比值(N L R)㊁红细胞体积分布宽度变异系数(R DW-C V)和红细胞体积分布宽度标准差(R DW-S D)等血常规炎症指标,癌胚抗原(C E A)㊁糖类抗原19-9(C A19-9)㊁甲胎蛋白(A F P)㊁细胞角蛋白19可溶性片段(C Y F R A)㊁神经元特异性烯醇化酶(N S E)㊁胃泌素释放肽前体(p r o-G R P)㊁总前列腺特异性抗原(t P S A)㊁游离前列腺特异性抗原(f P S A)和C A125等血清肿瘤标志物,以及L D H的数据㊂比较这些血液指标在3组间的差异,选取组间差异有统计学意义的指标进行受试者工作特征(R O C)曲线诊断分析,再选择曲线下面积(A U C)较大的指标用于进一步的联合诊断分析,最后应用二分类L o g i s t i c回归联合R O C曲线综合分析不同指标联合模式对肺癌的诊断能力㊂1.3统计学处理采用S P S S25.0软件进行数据分析㊂非正态分布的计量资料以中位数(四分位数)[M (P25,P75)]表示,两组间比较采用M a n n-W h i t n e y秩和检验分析,多组间比较采用K r u s k a l-W a l l i s秩和检验分析;采用R O C曲线分析单项检测指标对肺癌的诊断效能,多个指标联合的诊断则先用二分类L o g i s-t i c回归得出预测概率,再利用预测概率做R O C曲线分析;以P<0.05为差异有统计学意义㊂2结果2.1各组间血液检验指标的差异分析 P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A㊁C Y F R A在体检组㊁肺良性病变组㊁肺癌组之间的差异均有统计学意义(P<0.05)㊂见表1㊂2.2血液学检验指标对肺癌的诊断效能将肺良性病变组与体检组合并为对照组,应用R O C曲线分别评价在表1中组间差异有统计学意义的10项指标(P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A㊁C Y F R A)对肺癌的诊断效能,见表2㊂结果显示只有C Y F R A㊁L D H㊁P C T与R DW-C V4项指标的A U C>0.6,由于A U C<0.5没有诊断价值,在0.5~0.7时有较低的准确性,因此选择这4项指标作进一步的联合分析㊂2.3 P C T㊁R DW-C V㊁C Y F R A㊁L D H联合对肺癌的诊断效能将P C T㊁R DW-C V㊁C Y F R A㊁L D H进行相互联合,先对联合指标建立L o g i s t i c回归模型,再用形成的预测概率作为分析指标作R O C曲线,分析各种组合模式对肺癌的诊断效能㊂在2项指标联合模式中,L D H+C Y F R A诊断肺癌的A U C最大,为0.803,回归方程为L o g i t(P)=0.256-0.014ˑX L D H+0.704ˑX C Y F R A㊂3项指标联合模式中,R DW-C V+LD H+C Y F R A诊断肺癌的A U C最大,为0.823,回归方程为L o g i t(P)=-5.417+0.431ˑX R D W-C V-0.013ˑX L D H+0.689ˑX C Y F R A,灵敏度为74.5%,特异度为88.0%㊂P C T+R DW-C V+ L D H+C Y F R A检测的回归方程为L o g i t(P)= -5.032+3.185ˑX P C T+0.350ˑX R D W-C V+0.706ˑX C Y F R A-0.014ˑX L D H,A U C为0.821,灵敏度为76.5%,特异度为86.7%㊂P C T+R DW-C V诊断肺癌的特异度最高,为92.0%;P C T+R DW-C V+ L D H+C Y F R A诊断肺癌的灵敏度最高㊂见表3㊂表1血液检验指标在各组间的差异分析[M(P25,P75)]检测指标体检组(n=289)肺良性病变组(n=93)肺癌组(n=89)H PP L T(ˑ109/L)243(209,285)229(181,256)246(209,289)11.6990.003P D W(f L)11.50(10.75,12.65)11.60(10.25,15.80)11.75(10.7,13.50)1.8790.391 M P V(f L)10.20(9.70,10.80)9.60(9.00,10.20)10.20(9.60,10.90)28.865<0.001P C T(%)0.25(0.22,0.28)0.22(0.18,0.24)0.25(0.22,0.29)31.521<0.001N e u#(ˑ109/L)3.21(2.74,3.98)3.32(2.63,4.20)3.27(2.58,4.32)0.1940.908L y m#(ˑ109/L)1.78(1.53,2.05)1.94(1.59,2.53)1.80(1.53,2.25)8.1350.017N L R1.77(1.46,2.23)1.72(1.25,2.12)1.76(1.33,2.50)3.3830.184R D W-C V(%)12.20(11.90,12.67)12.50(12.15,13.00)12.60(12.10,13.20)14.3310.001R D W-S D(f L)40.30(38.75,42.40)41.20(39.80,43.35)41.80(39.90,43.70)11.8660.003L D H(U/L)194(174,214)212(195,253)184(157,207)10.9810.004㊃067㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6Copyright©博看网. All Rights Reserved.续表1血液检验指标在各组间的差异分析[M(P25,P75)]检测指标体检组(n=289)肺良性病变组(n=93)肺癌组(n=89)H P N e u%(%)59.10(54.40,63.10)55.10(49.00,62.00)57.40(51.40,65.00)6.4600.040 L y m%(%)33.20(27.90,37.40)32.50(29.10,38.20)33.00(25.9,38.70)1.1630.559 C E A(n g/m L)1.70(1.30,2.38)3.15(2.45,5.50)2.60(1.40,4.45)20.695<0.001 C A199(U/m L)10.17(6.92,14.01)10.58(8.14,21.30)9.80(7.15,19.08)1.0250.599 A F P(n g/m L)2.64(1.95,3.62)3.48(2.27,5.03)2.53(1.79,3.43)2.7480.253 C Y F R A(n g/m L)1.93(1.51,2.74)1.87(1.53,2.44)2.75(1.91,4.24)25.858<0.001 N S E(n g/m L)10.57(10.57,10.57)10.00(9.25,10.01)13.92(11.02,16.65)4.5700.102 p r o-G R P(n g/L)41.41(32.34,49.34)40.53(27.74,62.10)42.94(36.02,53.64)2.8440.241 T P S A(n g/m L)0.91(0.58,1.11)0.86(0.55,0.96)0.75(0.45,1.30)0.5150.773 F P S A(n g/m L)0.26(0.17,0.39)0.25(0.15,0.33)0.38(0.22,0.45)2.7550.252 C A125(U/m L)9.95(8.00,13.80)14.16(8.38,19.71)12.60(7.48,25.97)5.5420.063表23组间存在差异的血液学检验指标对肺癌的诊断效能检测项目A U C A U C的95%C I P灵敏度(%)特异度(%)正确指数c u t-o f f值C Y F R A0.7070.636~0.767<0.00158.673.10.3172.52n g/m LL D H0.6300.548~0.6920.00181.137.50.186153U/LP C T0.6260.567~0.672<0.00152.434.30.1330.24%R D W-C V0.6030.550~0.689<0.00143.272.50.15712.70%R D W-S D0.5970.558~0.6950.00145.569.10.14642.10f LM P V0.5960.523~0.646<0.00143.170.80.13910.30f LP L T0.5710.505~0.6480.01045.367.40.127253ˑ109/LN e u%0.5230.443~0.5860.41125.684.80.10464.85%L y m#0.4860.405~0.5480.20331.569.70.0122.14ˑ109/LC E A0.4450.389~0.5030.13935.287.70.2293.40n g/m L表3实验室指标联合对肺癌的诊断效能联合模式A U C A U C的95%C I P灵敏度(%)特异度(%)正确指数P C T+C Y F R A0.7080.640~0.769<0.00157.077.30.343 L D H+C Y F R A0.8030.708~0.876<0.00175.981.00.569 P C T+L D H0.6300.576~0.6730.00138.980.90.198 P C T+R D W-C V0.6600.597~0.652<0.00133.092.00.250 R D W-C V+C Y F R A0.7610.690~0.814<0.00171.076.20.472 R D W-C V+L D H0.6920.620~0.727<0.00167.565.50.330 P C T+C Y F R A+L D H0.8020.721~0.886<0.00175.981.00.569 P C T+R D W-C V+C Y F R A0.7610.695~0.819<0.00169.077.40.464 P C T+R D W-C V+L D H0.6930.640~0.747<0.00171.763.20.349 R D W-C V+L D H+C Y F R A0.8230.748~0.903<0.00174.588.00.625 P C T+R D W-C V+L D H+C Y F R A0.8210.745~0.899<0.00176.586.70.6323讨论鉴于血液具有窗口及镜像效应和易于取材的特点,可以反映人类机体的生理与病理状况,中国医学科学院血液病医院的程涛所长提出了 血液生态 这一概念[4]㊂从这一概念出发,本研究团队对肺癌的各种常规血液指标进行研究,以期能找到辅助肺癌早期诊断的简单㊁便捷的指标组合㊂肿瘤与炎症密切相关,慢性持续性炎症可导致通常静止的支气管肺泡干细胞增殖,并导致肺上皮细胞癌变[5]㊂近年来,血常规炎症指标在肿瘤中的应用备㊃167㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6Copyright©博看网. All Rights Reserved.受关注㊂已有多项研究将血常规炎症指标如P L T㊁P C T㊁M P V㊁P DW㊁N e u#㊁N e u%㊁L y m#㊁L y m%与R DW等应用于肺癌的诊断㊁进展及预后判断[6-13]㊂本研究结果显示,P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A和C Y F R A在3组间的差异有统计学意义(P<0.05)㊂O N C E L等[7]回顾性分析了44例肺癌患者的P L T㊁P C T㊁M P V和P DW值,并与47例健康受试者对比分析显示,肺癌组的P DW值明显高于对照组,而P C T和M P V的值低于对照组,P L T在两组间则没有差异,这与本研究结果不符㊂丛玉隆等[14]的调查表明,P L T在健康人群中与M P V呈反比,这从侧面验证了本研究的分析结果㊂N L R反映了中性粒细胞相关的促肿瘤炎症和淋巴细胞依赖的抗肿瘤免疫之间的潜在平衡,高N L R 可能反映了肿瘤免疫的失衡[15-16]㊂X U等[8]在非小细胞肺癌(N S C L C)人群中研究发现,术前N L R值明显高于健康对照人群,是早期诊断N S C L C的有效标志物,而本研究结果却显示N L R在3组间无明显差异㊂可能原因在于,该研究只分析了N S C L C患者与健康人群,而本研究的研究对象包含所有病理分型的肺癌患者㊁健康体检者与肺良性病变者㊂此外,R DW被证实可以作为胃癌㊁甲状腺癌㊁乳腺癌和前列腺癌等肿瘤筛查的辅助诊断指标[17-20];关于R DW与肺癌,有研究报道R DW是肺癌的独立预后因素且与其分期㊁转移等病理特征相关[11-12,21-22],也有研究报道R DW 可用于肺癌的早期诊断[23],与本研究结果基本一致㊂R O C曲线分析P L T㊁M P V㊁P C T㊁L y m#㊁R DW-C V㊁R DW-S D㊁L D H㊁N e u%㊁C E A和C Y F R A对肺癌的诊断效能,但只有P C T㊁C Y F R A㊁L D H㊁R DW-C V 的A U C>0.6,其中C Y F R A的A U C最高也仅有0.707,说明单项指标对肺癌的诊断效能均不理想㊂C E A㊁C A19-9㊁A F P㊁C Y F R A㊁N S E㊁P S A和C A125是临床常用的肺癌标志物㊂血清肿瘤标志物是由肿瘤细胞自身合成㊁释放或机体对肿瘤细胞反应而升高的一类物质,对肿瘤的诊断㊁疗效判断和复发监测具有一定价值㊂由于肿瘤标志物的敏感性㊁特异性和器官定位作用均不理想,主要用于疗效监测[24],对癌症的诊断价值有限㊂结合血常规炎症指标与血清肿瘤标志物或可提高对肺癌的早期诊断率㊂LD H是糖酵解途径中的关键酶,L D H升高是预后不良的一种生物标志物[25]㊂一篇包含28项研究的M e t a分析显示血清L D H升高与N S C L C患者总体生存率之间存在显著相关性[26]㊂本研究结果也显示L D H在肺癌诊断中具有一定的价值,但L D H是否可用于肺癌的早期诊断尚未可知㊂联合多项检测指标是提高疾病诊断准确度的有效措施㊂本研究将P C T㊁C Y F R A㊁L D H㊁R DW-C V相互联合,在11种联合模式中,R DW-C V+L D H+C Y-F R A诊断肺癌的A U C最高,可达0.823,高于P C T+R DW-C V+L D H+C Y F R A诊断肺癌的A U C (0.821),R DW-C V+L D H+C Y F R A诊断的灵敏度㊁特异度分别为74.5%㊁88.0%㊂但特异度最高的模式为P C T+R DW-C V,达92.0%;灵敏度最高的模式为P C T+R DW-C V+L D H+C Y F R A,达76.5%㊂为何P C T+R DW-C V的特异度最高,甚至超过了3项或4项指标的联合检测模式?2018年发表于‘N a t u r e“的一篇文章报道,研究人员分析了37例 前白血病患者 和262例健康人的血常规和生化检查数据,发现R DW升高是急性髓系白血病(AM L)的风险因素,基于上面的血液常规数据,他们用机器学习算法开发了一套预测模型,这个以R DW为主要指标的模型可以提前6~12个月预测AM L的发生,灵敏度为25.7%,特异度则为98.2%[27]㊂这与本研究结果类似,即P C T+R DW-C V诊断肺癌的特异度高(92.0%),但是灵敏度却只有33.0%㊂R DW是反映人体内数量最大的红细胞大小不一的参数㊂从血液生态的角度来看,血液系统是各组织器官之间互相合作的纽带和信息传递的 使者 ,而血常规是最能代表血液生态的一种检测,因此,鉴于血液生态的统一整体性,R DW这一指标能在疾病早期就发生变化,特异度高㊂L o g i s t i c回归属于概率型非线性回归,可客观地实现灵敏度与特异度的平衡㊂因此联合C Y F R A 与L D H这两项灵敏度较好的指标,通过L o g i s t i c回归构建的模型与R O C曲线结合,建立联合新指标的模型可提高诊断的综合效能㊂本研究存在的局限性:为单中心回顾性分析,会存在选择偏倚的问题;因收集数据不够全面,未能收集肺癌患者的病理学数据及诊疗随访信息,不能进一步分析这些血液学指标与肺癌患者病理学特征,如病理分型㊁分期或转移等的关系,也没有采用独立的验证队列来验证诊断的效能㊂不可否认的是血液学指标对肺癌的诊断效能不及影像学和病理活检技术,但是血液学指标有廉价易得㊁可重复操作的优势,且肿瘤标志物的灵敏度极高,或可对肺癌的早诊早治起一定的作用㊂综上所述,在众多常规血液学检验指标中,只有R DW-C V㊁P C T㊁L D H㊁C Y F R A对肺癌具有一定的诊断效能,其中联合R DW-C V㊁L D H㊁C Y F R A这3项指标对肺癌的临床诊断价值最大㊂参考文献[1]S U N G H,F E R L A Y J,S I E G E L R L,e t a l.G l o b a l c a n c e rs t a t i s t i c s2020:G L O B O C A N e s t i m a t e s o f i n c i d e n c e a n dm o r t a l i t y w o r l d w i d e f o r36c a n c e r s i n185c o u n t r i e s[J].㊃267㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6Copyright©博看网. 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[12]Z HA O W,S H I M,Z HA N G J.P r e o p e r a t i v e h e m o g l o b i n-t o-r e d c e l l d i s t r i b u t i o n w i d t h r a t i o a s a p r o g n o s t i c f a c t o r i n p u l m o n a r y l a r g e c e l l n e u r o e n d o c r i n e c a r c i n o m a:a r e t-r o s p e c t i v e c o h o r t s t u d y[J].A n n T r a n s l M e d,2022,10(2):42.[13]MA C,WA N G X,Z HA O R.A s s o c i a t i o n s o f l y m p h o c y t ep e r c e n t a g e a n d r e d b l o o d c e l l d i s t r i b u t i o n w i d t h w i t h r i s k o f l u n g c a n c e r[J].J I n t M e d R e s,2019,47(7):3099-3108.[14]丛玉隆,金大鸣,王鸿利,等.中国人群血小板各项参数的调查分析[J].中华检验医学杂志,2004,27(6):368-370.[15]G R I V E N N I K O V S I,G R E T E N F R,K A R I N M.I mm u-n i t y,i n f l a mm a t i o n,a n d c a n c e r[J].C e l l,2010,140(6): 883-899.[16]D U A N J,P A N L,Y A N G M.P r e o p e r a t i v e e l e v a t e d n e u-t r o p h i l-t o-l y m p h o c y t e r a t i o(N L R)a n d d e r i v e d N L R a r ea s s o c i a t e d w i t h p o o r p r o g n o s i s i n p a t i e n t s w i t hb r e a s tc a n c e r:A m e t a-a n a l y s i s[J].M ed i c i n e(B a l t i m o r e),2018,97(49):e13340.[17]B A I C U S C,C A R A I O L A S,R I M B A S M,e t a l.U t i l i t y o f r o u t i n e h e m a t o l o g i c a l a n d i n f l a mm a t i o n p a r a m e t e r s f o r t h e d i a g n o s i s o f c a n c e r i n i n v o l u n t a r y w e i g h t l o s s[J].JI n v e s t i g M e d,2011,59(6):951-955.[18]A K T A S G,S I T M,K A R A G O Z I,e t a l.C o u l d r e d c e l ld i s t r i b u t i o n w i d t h be a m a r k e r of t h y r o i d c a n c e r[J].JC o l l P h y s i c i a n s S u r g P a k,2017,27(9):556-558.[19]HU A N G T B,Z HU L Y,Z HO U G C,e t a l.P r e-t r e a t-m e n t r e d b l o o d c e l l d i s t r i b u t i o n w i d t h a s a p r e d i c t o r o f c l i n i c a l l y s i g n i f i c a n t p r o s t a t e c a n c e r[J].I n t U r o l N e p h-r o l,2021,53(9):1765-1771.[20]S U N H,Y I N C Q,L I U Q,e t a l.C l i n i c a l s i g n i f l c a n c e o fr o u t i n e b l o o d t e s t-a s s o c i a t e d i n f l a mm a t o r y i n d e x i nb r e a s tc a n c e r p a t i e n t s[J].M ed S c i M o n i t,2017,23:5090-5095.[21]Z HA N Z,F E I Z,X U B,e t a l.P r o g n o s t i c s i g n i f i c a n c e o f r e d c e l l d i s t r i b u t i o n w i d t h i n a d v a n c e d n o n-s m a l l c e l l l u n g c a n c e r p a t i e n t s[J/O L].C l i n L a b,[2022-09-28].h t t p s://p u b m e d.n c b i.n l m.n i h.g o v/33865247/.[22]MA C,WA N G X,Z HA O R.A s s o c i a t i o n s o f l y m p h o c y t ep e r c e n t a g e a n d r e d b l o o d c e l l d i s t r i b u t i o n w i d t h w i t h r i s k o f l u n g c a n c e r[J].J I n t M e d R e s,2019,47(7):3099-3108.[23]WA RW I C K R,M E D I R A T T A N,S HA C K C L O T H M,e ta l.P r e o p e r a t i v e r e d c e l l d i s t r ib u t i o n w i d t h i n p a t i e n t s u n-d e r g o i n g p u l m o n a r y r e s e c t i o n s f o r n o n-s m a l l-c e l l l u n g c a n c e r[J].E u r J C a r d i o t h o r a c S u r g,2014,45(1):108-113.[24]中华医学会检验分会,卫生部临床检验中心,中华检验医学杂志编辑委员会.肿瘤标志物的临床应用建议[J].中华检验医学杂志,2012,35(2):103-116.[25]A G R AWA L A,G A N D H E M B,G U P T A D,e t a l.P r e-l i m i n a r y s t u d y o n s e r u m l a c t a t e d e h y d r o g e n a s e(L D H)-p r o g n o s t i c b i o m a r k e r i n c a r c i n o m a b r e a s t[J].J C l i n D i-a g n R e s,2016,10(3):B c06-B c08.[26]WA N G L,C A O L,J I A N G R,e t a l.P r o g n o s t i c s i g n i f i-c a n c e o f c o m b i n ed b i o m a r ke r s i n s m a l l c e l l l u n g c a n c e r[J].C l i n L a b,[2022-09-28].h t t p s://p u b m e d.n c b i.n l m.n i h.g o v/32902217/.[27]A B E L S O N S,C O L L O R D G,N G S W K,e t a l.P r e d i c t i o no f a c u t e m y e l o i d l e u k a e m i a r i s k i n h e a l t h y i n d i v i d u a l s[J].N a t u r e,2018,559(7714):400-404.(收稿日期:2022-10-08修回日期:2023-02-02)㊃367㊃检验医学与临床2023年3月第20卷第6期 L a b M e d C l i n,M a r c h2023,V o l.20,N o.6Copyright©博看网. 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对比常规放疗与三维适形放射治疗（3D-CRT）乳腺癌的临床疗效、毒副作用
34·罕少疾病杂志 2023年3月 第30卷 第 3 期 总第164期【第一作者】张 倩，女，主管技师，主要研究方向：放射治疗。
E-mail：***************【通讯作者】胡立宏，男，副主任技师，主要研究方向：放射治疗、立体定向放射外科。
E-mail：*****************·论著·对比常规放疗与三维适形放射治疗(3D-CRT)乳腺癌的临床疗效、毒副作用张 倩 关佳恒 宋旭旭 胡立宏*联勤保障部队第989医院肿瘤科 (河南 洛阳 471000)【摘要】目的 对比常规放疗与三维适形放射治疗(3D-CRT)乳腺癌的临床疗效、毒副作用。
方法 选定本院2018年1月至2021年1月住院的90例乳腺癌患者，以随机法将其分组(每组n=45)，对比组给予常规放疗治疗，观察组给予3D-CRT治疗，对比两组局部复发率、血清肿瘤标志物、毒副反应总发生率，统计危及器官照射剂量。
结果 观察组局部复发率(2.22%)低于对比组(22.22%)，P <0.05(差异有统计学意义)。
观察组治疗后血清糖类抗原199(CA199)、糖类抗原125(CA125)、癌胚抗原(CEA)均低于对比组，P <0.05(差异均具有统计学意义)。
观察组毒副反应总发生率(8.89%)低于对比组(28.89%)，P <0.05(差异具有统计学意义)。
患侧肺V20、患侧肺V30、患侧肺V40、患侧肺V50、左侧心脏V30、左侧心脏V40、左侧心脏V50、分别是(15.28±2.62)cm 3、(10.15±3.96)cm 3、(1.85±0.62)cm 3、(0.54±0.26)cm 3、(2.52±1.25)cm 3、(2.24±0.99)cm 3、(0.45±0.13)cm 3。
结论 3D-CRT可有效抑制乳腺癌患者肿瘤病灶生长，降低局部复发率、血清肿瘤标志物浓度，同时可减少危及器官照射剂量，减轻毒副反应。
核磁共振弥散加权成像联合血清肿瘤标志物检测在乳腺癌诊断中的应用
核磁共振弥散加权成像联合血清肿瘤标志物检测在乳腺癌诊断中的应用摘要：目的：研究核磁共振弥散加权成像联合血清肿瘤标志物检测在乳腺癌诊断中的应用价值。
方法：本次选择了我院在2019年1月至2020年1月检查78名女性，其中，选择了26名同期体检健康者为对照组，并选择26名乳腺良性肿瘤患者、26名乳腺癌患者作为研究对象，将这些患者根据病症情况分为乳腺良性肿瘤组与乳腺癌组。
通过观察三组血清肿瘤标志物水平比较、不同检查方式对乳腺癌的诊断效果，得出研究结论。
结果：①三组血清肿瘤标志物水平乳腺癌组在三组血清肿瘤标志物水平（四项指标）与对照组、良性肿瘤组存在较大差异。
（P<0.05，差异具有统计学意义）而良性肿瘤组与对照组在这四项指标上并无太大差异。
（P>0.05，无统计学意义）②单独应用ＭＲ检查的敏感度、特异度、准确度分别为69.23%、50.00%、61.54%。
单独应用血清肿瘤标志物检查的敏感度、特异度、准确度分别为57.69%、46.15%、38.46%。
联合应用ＭＲ和血清肿瘤标志物检查的敏感度、特异度、准确度分别为88.46%、84.62%、84.62%。
（P<0.05，差异具有统计学意义）结论：联合应用ＭＲ和血清肿瘤标志物检查更加准确，值得推广。
关键词：核磁共振；血清肿瘤标志物检测；乳腺癌；加权成像；诊断Application of nuclear magnetic resonance diffusion-weighted imaging combined with serum tumor markers in the diagnosis of breast cancerAbstract: Objective: To study the application value of nuclear magnetic resonance diffusion-weighted imaging combined with serum tumor markers detection in the diagnosis of breast cancer.Method: the choice of our hospital in January 2019 to January 2020 to check 78 women, among them, chose the same period of 26 medical healthysubjects as control group, and select the 26 patients with breast benign tumors, 26 patients with breast cancer as the research object, according to the condition in patients with these can be pided into benign breast tumor and breast cancer groups.By observing the comparison of serum tumor markers and different examination methods for the diagnosis of breast cancer in three groups, the conclusion was drawn.Results: There were significant differences in serum tumor markers (four indicators) between the breast cancer group and the control group and the benign tumor group.(P<There was no significant difference in these four indicators between the benign tumor group and the control group.(P>The sensitivity, specificity and accuracy of MR alone were 69.23%, 50.00% and 61.54%, respectively.The sensitivity, specificity and accuracy of serum tumor markers were 57.69%, 46.15% and 38.46%, respectively.The sensitivity, specificity and accuracy of MR and serum tumor markers were 88.46%, 84.62% and 84.62%, respectively.(P<Conclusion: The combined application of MR and serum tumor markers is more accurate and worthy of promotion.Keywords: NUCLEAR magnetic resonance;Detection of serum tumor markers;Breast cancer;Weighted imaging;diagnosis引言乳腺癌是严重威胁女性生命健康的恶性肿瘤之一，乳腺癌发病早期多无症状，就诊时病期已相对较晚，而病灶的进一步转移又常常是致使乳腺癌治疗失败的主要原因[1]。
人附睾分泌蛋白4诊断子宫内膜癌的价值meta分析
人附睾分泌蛋白4诊断子宫内膜癌的价值meta分析郑建清; 黄碧芬; 吴敏; 陈明芬; 肖丽华【期刊名称】《《黑龙江医学》》【年(卷),期】2019(044)009【总页数】3页(P1136-1138)【关键词】子宫内膜癌; 人附睾分泌蛋白4; 诊断试验; Meta分析【作者】郑建清; 黄碧芬; 吴敏; 陈明芬; 肖丽华【作者单位】福建医科大学附属第二医院放射治疗科福建泉州 362000; 泉州医学高等专科学校附属人民医院妇产科福建泉州 362000【正文语种】中文【中图分类】R446.11子宫内膜癌（Endometrial cancer，EC）是西方发达国家最常见的妇科恶性肿瘤，其发病率位居女性常见肿瘤第四位，仅次于乳腺癌、结直肠癌和甲状腺癌［1-2］。
在我国子宫内膜癌发病率仅次于子宫颈癌，占女性生殖道恶性肿瘤的20%～30%，最新一项流行病学资料显示，子宫内膜发病率位居老年妇女恶性肿瘤的第十位，新发病例2.11 万人，年发病率约19.41/10 万［3］。
肿瘤标志物在子宫内膜癌早期诊断中的作用仍然存在争议。
人附睾蛋白4（Human epididymis protein 4，HE4）是一种新型的肿瘤标志物，它存在于血液循环中，并已被证实在多种妇科恶性肿瘤患者中过度表达；Moore 等［4］已经证实血清HE4 在子宫内膜癌的各个肿瘤分期中均升高，并且在早期子宫内膜癌中比CA125更敏感。
鉴于目前对HE4是否可以常规用于子宫内膜癌筛查仍存在争议，而且已发表的关于HE4诊断子宫内膜癌的研究均为小样本研究，本文收集目前已发表的文献，从meta 分析的角度，系统评价HE4 早期诊断子宫内膜癌的准确率。
1 资料与方法1.1 纳入与排除标准1.1.1 研究类型：国内外公开发表的关于HE4诊断子宫内膜癌的诊断性试验，研究设计仅限前瞻性研究。
1.1.2 研究对象：子宫内膜癌，分期及具体病理类型不限。
1.1.3 诊断方法：待评价试验为HE4诊断子宫内膜癌的诊断性试验，以病理学诊断结果为金标准。
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RESEARCH ARTICLEUtility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancerand in patients with cancer of unknown primary siteRafael Molina&Xavier Bosch&Josep M.Auge&Xavier Filella&JoséM.Escudero&Víctor Molina&Manel Solé&Alfonso López-SotoReceived:2August2011/Accepted:10November2011#International Society of Oncology and BioMarkers(ISOBM)2011Abstract Cancer may be diagnosed in advanced stages, when the patient has already developed metastasis,with symptoms that can be also observed in benign diseases.The objective of this study was to evaluate tumor marker sensitivity and specificity in the differential diagnosis of patients with suspected signs of cancer.We studied2.711 consecutive patients admitted to the Internal Medicine Department of our hospital with suspected cancer;1.240 patients had non-malignant processes and1.471had malig-nant disease.Determinations were considered positive for suspected malignancy when serum levels were carcinoem-bryonic antigen>15ng/ml(>20in patients with renal failure or liver disease),alpha fetoprotein>40ng/ml(>80ng/ml in patients with liver diseases),carbohydrate antigen(CA)19.9> 200U/ml(>500U/ml in patients with liver diseases or gamma glutamyl transpeptidase(GGT)<150UI/L or effusions; >1.000U/ml in patients with jaundice or GGT>150UI/L), neuron-specific enolase>45ng/ml(renal failure>50ng/ml; samples with hemolysis were excluded),prostate-specific antigen>30ng/ml(excluding acute prostatitis),tumor-associated glycoprotein-72>80U/ml,cytokeratin19frag-ment21-1>7.5ng/ml(>19ng/ml in patients with renal failure;>11ng/ml in patients with liver cirrhosis or jaundice),>3.5ng/ml for squamous cell carcinoma(exclud-ing patients with renal failure or skin disorders),CA15.3 >100U/ml,and CA125>350U/ml(>600U/ml in patients with pleural effusion and>900U/ml in those with ascites). There was a specificity of97.6%in patients without malignancy,67.4%of sensitivity in patients with malignan-cy,and75.4%of sensitivity in the1,280patients with epithelial tumors(53.7%in patients with locally advanced tumors and79.4%in patients with metastases).Sensitivity was81.4%in patients with cancer of unknown primary site. Tumor markers were useful in the differential diagnosis between epithelial and non-epithelial tumors,brain masses (metastases vs.primary tumors),and between benign or malignant origin of different clinical situations such as wasting syndrome,effusions,liver or bone lesions,and effusions with a positive predictive value higher than95%. Tumor markers are useful as an aid in the evaluation of the risk of cancer of these patients with suspected cancer and may be useful to reduce the hospitalization time,morbidity,and the number of diagnostic tests required for diagnosis. Keywords Cancer of unknown primary site.Tumor markers.CEA.CA125.CA19.9 R.Molina(*):J.M.Auge:X.Filella:J.M.EscuderoLaboratory of Clinical Biochemistry(Unit for Cancer Research),Hospital Clinic,Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS),University of Barcelona,Villarroel170,Barcelona08036,Spaine-mail:rmolina@clinic.ub.esX.Bosch:A.López-SotoDepartment of Internal Medicine,Hospital Clinic,Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS),University of Barcelona,Barcelona,SpainV.MolinaDepartment of Surgery,Hospital Clinic,Institut d’Investigacions Biomèdiques August Pi iSunyer(IDIBAPS),University of Barcelona,Barcelona,SpainM.SoléDepartment of Pathology,Hospital Clinic,Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS),University of Barcelona,Barcelona,SpainTumor Biol.DOI10.1007/s13277-011-0275-1IntroductionCancer diagnosis and survival is related to tumor origin and stage.Early stages have a better prognosis,and therefore, an early diagnosis is A studies show the substantial costs of cancer care to Medicare vary by tumor site,phase of care,stage at diagnosis,and survival[1,2]. An important number of patients with cancer are diagnosed in advanced state.These patients commonly present non-specific symptoms and signs such as wasting syndrome, bone pain,and hemoptysis,among others,although some are finally diagnosed with benign disease.These patients are usually hospitalized,spending several days undergoing multiple diagnostic tests.Hospitalizations represent the single largest cost component for most tumor types, although the intensity varies by tumor site[2,3].While some patients are diagnosed with well-defined cancers, 2–5%of all newly diagnosed patients with solid malignan-cies are classified as having cancer of unknown primary site (CUP)[4–6].Serum tumor markers are not specific for malignancy, and serum concentrations are clearly related to tumor stage [7–14].Their sensitivity in locoregional diseases is usually low,with levels frequently similar to those found in benign diseases[8–10,15].In contrast,tumor marker sensitivity and serum levels are significantly higher in patients with advanced disease,especially in those with metastases [7–11,16–19].Tumor markers are commonly used in the early diagnosis of recurrence of several malignancies,with a high sensitivity and specificity[16,17]as well as in therapy monitoring.The utility of tumor markers in the differential diagnosis of patients hospitalized with signs and symptoms suggestive of advanced cancer has not been evaluated,although,since their sensitivity is high,they may be useful.The aims of this study were:1.To look for a cutoff useful to differentiate in patientswith suspicious signs of cancer those with malignancy from those with benign diseases2.To establish the tumor marker sensitivity in patientswith locally advanced or metastatic cancer at diagnosis, according to the tumor origin3.To evaluate the tumor marker sensitivity and specificityin patients admitted in the hospital with paraneoplastic syndromes or symptoms frequently associate to cancer Patients and methodsWe included2.711consecutive patients admitted to the Internal Medicine Department of our hospital with sus-pected cancer between March2000and May2006.In addition to a diagnostic workup,which differed according to the reason for consultation,all patients underwent a full serum panel of tumor markers.The final diagnosis was non-malignancy in1.240and malignancy in1.471.Clinical manifestations of the 2.711patients on admittance are shown in Table1.Patients without malignancy included in the study(1.240),including those with a former history of malignancy(130),had no evidence of cancer after a mean follow-up of57.3months(range48–96months).Ninety of these patients with malignancy died in the first2months for the disease;meanwhile,follow-up was performed in1,150, confirming that no malignancy was diagnosed in the next 12months of patient inclusion.Of the patients without malignancy(median age66.2±14.2,range17–100years)included680males(median age 65.7±13.8,range20–99years)and560females(median age66.7±14.7,range17–100years);of these,130(49 females,81males)had a previous history of malignancy, but no evidence of disease at the current evaluation.A total of316patients(25.5%)were smokers,241(19.4%)were former smokers,and683(55.1%)were non-smokers.The final diagnosis was lung disease in305patients(infectious 143,tuberculosis40,pulmonary thromboembolism25, chronic obstructive pulmonary disease in67,others30), liver diseases in81patients(40liver cirrhosis,22hepatitis, 19cholelitiasis),heart disease in151patients(myocardial infarction in37,dilated cardiomyopathy45,congestive heart failure in58,others11),neurological disorders in132 patients(stroke in52patients,brain abscess5,dementia7, cerebral hematoma12,anxiety20,others36),renal disease in40patients(renal failure in24,renal colic4,infections urinary abscess12),digestive disease in81patients(12 with pancreatitis,peptic ulcer10,gastroenteritis9,inflam-matory bowel disease23,polyps10,others17),autoim-mune disease in35patients,endocrine disorders in25 (diabetes8,thyroid disease17),skin disorders in61 patients(24with dermatomyositis,8psoriasis,8pemphigus, 9eczema,12other diseases),benign tumors in60patients (24gynecological tumors,7pituitary adenomas,29others), musculoskeletal diseases in111patients(arthrosis48, osteoporosis18,bone pain26,pathologic fracture7,others 12),pulmonary thromboembolism in49,anemia in17 patients,fever in16patients,AIDS in three patients,other infectious diseases in29patients(15sepsis),and the remaining40patients with other benign diseases(14 inflammatory)and benign prostatic hyperplasia in the remaining4patients.Of the1.471patients with malignancy,593were female (median age68±13.7years,range23–94)and878male (median age66.2±13years,range15–92);549(37.3%) were smokers,279former smokers(19%),and643non-smokers(43.7%).Tumor stage was established according to previously established criteria including the WHO classifi-Tumor Biol.cation of hematological malignancies[18].Table2shows the origin and tumor stage of the 1.471patients with confirmed malignancy.Of the1.159patients with malig-nancy of known origin,450were female(median age67.7Table1Signs and symptoms observed in patients admitted with suspicious of malignancyNo.of patients benign diseases/rate No.of patientsmalignancy/rateTotal%ofmalignancyWasting syndrome232(18.7%)297(20.2%)529(56.1%) Pulmonary thromboembolism22(1.8%)9(0.6%)31(29%) Asthenia22(1.8%)3(0.22%)25(12%) Dermatological diseases(dermatomyositis and pemphigus)41(3.3%)10(0.7%)51(19.6%) Fever50(4%)31(2.1%)81(38.3%) Jaundice6(0.5%)13(0.9%)19(68.4%) Anemia21(1.7%)15(1%)36(41.7%) Hemoptysis6(0.5%)5(0.3%)11(45.5%) Hematuria1(0.1%)7(0.5%)8(87.5%) Metrorrhagia5(0.4%)6(0.4%)11(54.5) Rectorrhagia15(1.2%)7(0.5%)22(31.8%) Ascites14(1.1%)66(4.5%)80(82.5%) Pleural effusion35(2.8%)59(4%)94(62.8%) Pericardial effusion9(0.7%)2(0.1%)11(18.2%) Dyspnea218(17.6%)152(10.3%)370(41%) Liver mass11(0.9%)86(5.8%)97(88.7%) Lung mass39(3.1%)86(5.8%)125(68.8%) Bone image14(1.1%)42(2.9%)56(75%) Central nervous system mass6(0.5%)24(1.6%)30(80%) Abdominal mass8(0.6%)22(1.5%)30(73.3%) Mediastinal mass5(0.4%)10(0.7%)15(66.7%) Cutaneous mass5(0.4%)4(0.3%)9(44.4%) Other masses8(0.6%)11(0.7%)19(57.9%) Lymphadenopathy21(1.7%)84(5.7%)105(80%) Other gastrointestinal disorders19(1.5%)12(0.8%)31(38.7%) Cough5(0.4%)6(0.4%)11(54.5%) Thoracic pain51(4.1%)32(2.2%)83(38.6%) Bone pain49(4%)81(5.5%)130(62.3%) Lumbar pain54(4.4%)39(2.7%)93(41.9%) Abdominal pain42(3.4%)63(4.3%)105(60%) Headache20(0.8%)19(1.3%)39(48.7%) Pathologic fracture8(0.6%)14(1%)22(63.6%) Epilepsy13(1%)14(1%)27(51.9%) Disorientation22(1.8%)20(1.4%)42(47.6%) Loss of consciousness20(1.6%)10(0.7%)30(33.3%) Dysarthria6(0.5%)20(1.4%)26(76.9%) Polyneuropathy11(0.9%)27(1.8%)38(71.1%) Neuromuscular disorders37(3%)13(0.9%)50(26%) Sight disorders18(14%)19(1.3%)37(51.4%) Gait disorders16(1.3%)15(1%)31(48.4%) Dysphagia4(0.3%)5(0.3%)9(55.6%) Other benign diseases27(2.1%)4(0.3%)31(12.9%) Abnormal tumor markers4(0.3%)7(0.5%)11(63.6%) Total1,2401,4712,711 Tumor Biol.±14years,range23–94years)and709male(median age 66.5±13years,range15–92years).Of these patients,507 (43.7%)were non-smokers,229(19.7%)former smokers, and423(36.5%)smokers.Of the312CUP patients,143 were females(68.9±12.9years,range29–92)and169 males(64.7±12.7years,range33–87years);123(39.4%) were smokers,138(44.2%)non-smokers,and51(16.4%) former smokers.Tumor markers were determined within3days of admission.All patients finally diagnosed with malignancy had biopsy-proven confirmation.Likewise,CUP patients also had a complete diagnostic workup and a histolog-ically confirmed diagnosis.Tumor markers studied were carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125),cancer antigen15-3(CA15-3),carbo-hydrate antigen19-9(CA19-9),tumor-associated glycoprotein72(TAG-72or CA72.4),squamous cell carcinoma(SCC),alpha fetoprotein(AFP),cytokeratin 19fragment(CYFRA21-1),neuron-specific enolase (NSE),and prostate-specific antigen(PSA)in males.All tumor markers were evaluated using commercially available electroluminescent techniques:CEA,CA125, CA15.3,NSE,CA72.4,and CYFRA21-1by Roche (Elecsys);AFP and CA199by Siemens(Inmuno1until 2007,Centaur after2007);SCC by Abbott Laboratories (ImX);and PSA by Beckman Coulter.Criteria Determinations were considered positive for sus-pected malignancy when levels were:CEA>15ng/ml(>20 in patients with renal failure or liver disease),AFP>40ng/ ml(>80in patients with liver diseases),CA19.9>200U/ml (>500U/ml in patients with liver diseases or gamma glutamyl transpeptidase(GGT)<150UI/L or effusions; >1.000U/ml in patients with jaundice or GGT>150UI/L), NSE>45ng/ml(renal failure>50mg/ml;samples with hemolysis were excluded),PSA>30ng/ml(excluding acute prostatitis),CA72.4>80ng/ml,CYFRA21-1 >7.5ng/ml(>19ng/ml in patients with renal failure; >11ng/ml in patients with liver cirrhosis or jaundice), >3.5ng/ml for SCC(excluding patients with renal failure or skin disorders),CA15.3>100U/ml,and CA 125>350U/ml(>600U/ml in patients with pleural effusion and>900U/ml in those with ascites).Statistical analysis The Kolmogorov–Smirnov goodness-of-fit test was used to compare ordinal data,and the Wilcoxon rank sum test was used to compare continu-ous data.Sensitivity was calculated by dividing the number of patients with malignancy with elevated marker levels by the total number of patients with malignancy.Specificity was calculated by dividing the number of patients without malignancy and normal tumor marker values by the total number of patients without malignancy.Positive predictive value(PPV)was calculated by dividing patients with elevated tumor markers and malignancy by all patients with elevated tumor markers.Negative predictive value was calculated by dividing patients with negative results and no malignancy by all patients with negative results. Concordance was considered as the sum of patients with elevated tumor marker and malignancy and patients with normal tumor marker concentrations and no malignancy divided by the total number of patients and multiplied by100.Table2Patients with malignancies:origin and tumor stageTumor origin Locoregional(Mo orstages I–III)Advanced (metastasesor stage IV)TotalLung NSCLC88210298SCLC127789Head and neck51722Breast24244Ovarian24244Cervical3912Endometrial51116Colorectal1784101Gastric44347Esophagus3710Pancreas107282Cholangioma41317Liver162844Other digestive tract358Prostate93645Testicular123Penile213Bladder42024Renal72532Thyroid134Neuroendocrine32023CUP0312312Melanoma01212Other cutaneous101Mesothelioma347Sarcoma61622Thymoma415Glioblastoma19322Other central nervous system15015Lymphomas344175Leukemia718Myeloma02424Total2901,1811,471NSCLC non-small cell lung cancer,SCLC small cell lung cancer,CUPcancer of unknown primary siteTumor Biol.ResultsTable3shows tumor marker serum concentrations in patients with the final diagnosis of non-malignancy.Liver disease and renal failure were a common source of false positive results.CA19.9was clearly associated with liver disease,with significantly higher concentrations in patients with cholestasis compared with those with other liver diseases(p=0.001).Dermatological disorders clearly influ-enced SCC concentrations,and there was a non-significant trend to an association with higher levels of CYFRA21-1. Effusions were a source of false positive results,mainly for CA125.CA125serum concentrations were related to the type of effusion,with significantly higher concentrations in pleural compared with pericardial effusions and higher levels in patients with ascites compared with patients with other effusions.NSE,CA199,and CA15.3were also related to effusions,yet only slightly higher serum concen-trations were found and a second cutoff was not necessary.Table3shows that using different cutoffs according to the tumor marker and concomitant pathologies,it is possible to obtain a high specificity.False positive results in non-malignant patients ranged from0%for AFP to2% for CA19.9in patients with cholestasis.Only SCC showed significantly higher levels in patients with renal failure or dermatological disorders,with a wide range of results that did not permit a cutoff to distinguish between benign and malignant diseases.The overall specificity was higher than 99.4%(Table3),with some tumor marker being abnormal in30of1.240(2.4%)patients.Only one patient,who had chronic hepatitis,corticoid-related myopathy,respiratory over-infection,and abnormal levels of CYFRA21-1 (14ng/ml)and SCC(10ng/ml),had a false positive for two tumor markers.Tables4and5show tumor marker levels in patients with malignancy according to tumor origin.Significantly higher tumor marker concentrations were found in patients with epithelial tumors compared with patients with non-malignant diseases(p<0.004).Globally,tumor marker sensitivity in epithelial tumors(1.280patients)was: CYFRA21-149.9%,CEA36.2%,CA19.920.6%,NSE 16.9%,CA15.316%,CA12514.9%,CA72.412.6%, SCC7.3%,AFP 4.2%,and PSA 3.2%.Tumor marker serum levels were related to tumor stage,with significantly higher serum levels in patients with metastases than in those without,with the majority of tumor markers(p= 0.001),excluding PSA(p=0.087)and AFP(no differ-ences).One or another tumor marker hinted at malignancy in73.6%(712of968)of patients with epithelial malignan-cies of known origin,in78.7%(604of767)of patients with metastatic disease,and in53.7%(108of201)of those without metastases.On the other hand,tumor markers were negative in315(24.6%)patients with epithelial tumors,and only one tumor marker was suggestive of malignancy in 361(28.2%),two tumor markers in260(20.3%),and≥3 markers in344(26.9%)patients.Tumor marker sensitivity was associated with tumor origin.CEA,for example,had a sensitivity ranging from 42.6%in non-small cell lung cancer(NSCLC)patients to 0%in neuroendocrine tumors(NETs)(Table4).Some malignancies,including prostatic cancer,NETs,and hepa-tocellular carcinoma(HCC),had a specific pattern of tumor markers.Prostatic cancer frequently showed abnormal PSA (86.7%of patients)and negativity of the majority of tumor markers(CA125,CA199,CA72.4,and SCC)or with small increases in less than5%of the patients(CEA, CA15.3,and NSE).Similar results were found in NETs where NSE was the most sensitive tumor marker with abnormal serum levels in65.2%of the patients and negativity(<5%)of other tumor markers excluding AFP or CYFRA21-1.HCC had AFP as the most sensitive tumor marker and negativity or less than5%of sensitivity of the majority of tumor markers(CEA,CA125,CA15.3,CA 199,CA72.4,PSA,and SCC).Abnormal PSA was only found in one patient with bladder cancer invading the prostate.In contrast,AFP,the most sensitive tumor marker in HCC,had an intermediate specificity with abnormal levels in less than5%of prostatic tumors and digestive tract tumors.NSE,the tumor marker of choice in NET tumors and small cell lung cancer(SCLC)(sensitivity79.8%),may also be abnormal in several malignancies both epithelial (digestive tract,mainly HCC and pancreatic cancer)and non-epithelial(sarcomas and lymphomas).Excluding CUP, abnormal NSE levels were found in160patients:SCLC or NETs in86(53.8%)patients and other malignancies in74 (46.2%)patients.Table4also shows tumor marker sensitivity in patients with CUP.Tumor marker sensitivity ranged from48.1% with CYFRA21-1or40.4%with CEA to0.6%with PSA. In general,all tumor markers,excluding PSA,AFP,and SCC,had sensitivity higher than15%.One or another tumor marker was suggestive of malignancy in81.4%of the patients.There was a non-significant trend to higher concentrations in patients with CUP than in epithelial tumors of known origin(excluding PSA),which was significant with NSE,CA15.3,CYFRA21-1(p=0.001), and SCC(p=0.05).These results are somewhat similar when only epithelial tumors of known origin with metas-tases were compared with CUP(CA15.3and CYFRA21-1: p=0.001;NSE:p=0.034).In contrast,significantly higher PSA concentrations were found in epithelial tumors of known origin than in CUP(p=0.001).Some tumor markers such as CEA,SCC,AFP,or PSA were always negative in non-epithelial tumors(Table5).In contrast,mucins were usually negative in non-epithelial tumors excluding lymphomas where the majority ofTumor Biol.T a b l e 3S e r u m t u m o r m a r k e r s i n 1,240p a t i e n t s w i t h t h e f i n a l d i a g n o s i s o f n o n -m a l i g n a n c y ,s u b d i v i d e d a c c o r d i n g t o t h e d i f f e r e n t c r i t e r i a u s e dG r o u p a n d c u t o f fN o .o f p a t i e n t s p o s i t i v e /t o t a l M e d i a n ±S D P e r c e n t i l e 99R a n g e P v a l u eP S A M e n (>30n g /m l )679/680(99.9%)1.1±0.224.40.1–70T A G T o t a l g r o u p (>80U /m l )1,236/1,240(99.7%)1+0.540.40.1–393A F PW i t h o u t l i v e r d i s e a s e (>40n g /m l )797/797(100%)2±0.191–230.001W i t h l i v e r d i s e a s e s (>80n g /m l )444/444(100%)2+0.333.61–57C E AN o r e n a l f a i l u r e o r l i v e r d i s e a s e (>15n g /m l )628/628(100%)2±0.1110.1–14R e n a l f a i l u r e (>20n g /m l )284/284(100%)3±0.2180.3–230.001L i v e r d i s e a s e w i t h o u t r e n a l f a i l u r e (>20n g /m l )328/328(100%)2.5±0.215.30.1–170.001C A 19.9W i t h o u t l i v e r d i s e a s e s o r e f f u s i o n (>200U /m l )556/557(99.9%)9±1.294.31–518L i v e r d i s e a s e s w i t h o u t j a u n d i c e (>500U /m l )344/345(99.7%)18±4.24841–7510.001J a u n d i c e o r G G T >150U /L (>1,000U /m l )97/99(98%)28±483,5141–3,5140.009E f f u s i o n s ,w i t h o u t l i v e r d i s e a s e (>500U /m l )105/105(100%)12±5.9421.81–4220.045R e n a l f a i l u r e w i t h o u t l i v e r d i s e a s e o r e f f u s i o n s (>200U /m l )134/134(100%)13±1.7121.31–1290.038S C CN o d e r m a t o l o g i c a l o r r e n a l d i s e a s e (>3.5n g /m l )885/891(99.3%)0.5±0.13.30.1–16R e n a l f a i l u r e (e x c l u d e d )248/284(87.3%)1.1±0.329.60.1–690.0001D e r m a t o l o g i c a l d i s o r d e r w i t h o u t r e n a l f a i l u r e (e x c l u d e d )43/65(66.1%)1±1390.1–390.0001C Y F R A 21-1W i t h o u t r e n a l f a i l u r e o r l i v e r d i s e a s e o r s k i n d i s e a s e s (>7.5n g /m l )582/584(99.7%)1.45±0.160.1–12R e n a l f a i l u r e (>19n g /m l )2/284(0.7%)2.4±0.418.50.1–1180.001L i v e r d i s e a s e s w i t h o u t r e n a l f a i l u r e (>11n g /m l )2/328(0.6%)1.8±0.18.70.2–300.008S k i n d i s e a s e s ,w i t h o u t r e n a l o l i v e r d i s e a s e s (>7.5n g /m l )0/44(0%)1.7±0.27.10.3–7.10.072N S EW i t h o u t r e n a l o r l i v e r d i s e a s e s o r e f f u s i o n s >45n g /m l 0/557(0%)10±0.231.43–41R e n a l f a i l u r e (>50n g /m l )0/284(0%)12±0.4455–480.001E f f u s i o n s >45n g /m l 0/171(0%)12±0.532.74–370.001L i v e r d i s e a s e s w i t h o u t r e n a l f a i l u r e o r e f f u s i o n s >45n g /m l 0/228(0%)11±0.434.14–440.011C A 15.3W i t h o u t r e n a l o r l i v e r d i s e a s e s o r e f f u s i o n s (>100/U /m l )0/557(0.2%)16+0.4433–950.001R e n a l f a i l u r e (>100/U /m l )0/284(0%)20±0.781.33–900.001L i v e r d i s e a s e w i t h o u t r e n a l f a i l u r e (>100/U /m l )0/328(0%)19±0.671.34–940.001E f f u s i o n s ,w i t h o u t r e n a l o r l i v e r d i s e a s e (>100/U /m l )0/71(0%)20±1.6844–840.01C A 125W i t h o u t r e n a l f a i l u r e ,l i v e r d i s e a s e o r e f f u s i o n s (>350U /m l )0/557(0%)13±1110.41–289L i v e r d i s e a s e n o e f f u s i o n o r e n a l f a i l u r e (>350U /m l )1/228(0.4%)19±2.9227.83–4770.001E f f u s i o n s 7/258(2.7%)106.5±17.41,6663–2,3100.0001P e r i c a r d i a l e f f u s i o n a n d e d e m a s >350(U /m l )0/43(0%)69±12.73345–3340.01P l e u r a l e f f u s i o n (>600U /m l )2/158(1.3%)99±10.2736.45–868A s c i t e s (>900U /m l )5/57(8.8%)276±642,3103–2,3100.0001R e n a l d i s e a s e w i t h o u t e f f u s i o n s (>600U /m l )0/197(0%)21±3.82802–5010.001Tumor Biol.T a b l e 4T u m o r m a r k e r s i n p a t i e n t s w i t h a f i n a l d i a g n o s i s o f e p i t h e l i a l c a n c e r ,s u b d i v i d e d a c c o r d i n g t o t h e o r i g i nT u m o r /n o .o f p a t i e n t sN S C L C /298S C L C /89H e a d a n d n e c k /22D i g e s t i v e /265H C C /44P r o s t a t e /45O t h e r u r o l o g i c a l /62G y n e c o l o g i c /116N E T s /23C U P /312C E A ,n g /m l %p o s i t i v e127(42.6%)31(34.8%)2(9.1%)142(53.6%)1(2.3%)2(4.4%)4(6.5%)27(23.3%)0(0%)126(40.4%)M e d i a n10±339.2±1502±2.526±1692.5±0.83±1.12.7±2.34±1732.4±0.58.9±69.2R a n g e0.1–8,0050.2–13,0001–480.3–27,0000.8–280.6–360.4–1300.3–20,0560.5–100.3–13,000C A 125,U /m l %p o s i t i v e39(13.1%)3(3.4%)0(0%)40(15.1%)1(2.3%)0(0%)1(1.6%)38(32.8%)1(4.3%)68(21.8%)M e d i a n56±4655±25623±1369±10686±10718±7.424±14139±25636±88117.5±64.3R a n g e4–8,3934–22,8007–2904–20,0002–3,4202–2585–5603–17,0719–1,9345–8,950C A 19.9,U /m l %p o s i t i v e31(10.4%)8(9%)0(0%)127(47.9%)0(0%)0(0%)4(6.5%)11(9.5%)0(0%)83(26.6%)M e d i a n23±80.429±9814±20.2527±9,78462±2213±318.5±11622±11980±2747±5,080R a n g e1–15,9491–5,5003–4501–2,120,0001–5221–961–6,8231–12,73010–6001–1,520,000C A 15.3,U /m l %p o s i t i v e50(16.8%)1(1.1%)0(0%)21(7.9%)1(2.3%)1(2.2%)4(6.5%)45(38.8%)1(4.3%)81(26%)M e d i a n32.5±6.622±221.5±123±4.823±3.220±2.422±757±3618±5.340±15.5R a n g e8–1,2984–14212–317–8526–1265–1077–3408–3,6607–1265–2,780C A 72.4,U /m l %p o s i t i v e33(11.1%)0(0%)0(0%)63(23.8%)0(0%)0(0%)1(1.6%)14(12.1%)0(0%)50(16%)M e d i a n3.1±41.61±0.51±1.59.7±501±0.62±0.81±1.83±95.11±0.83±206R a n g e0.1–11,6000.1–280.2–280.1–8,8810.1–240.1–320.1–970.1–9,3000.2–180.1–63,000N S E ,n g /m l %p o s i t i v e7(2.3%)71(79.8%)1(4.5%)38(14.3%)5(11.4%)1(2.2%)5(8.1%)6(5.2%)15(65.2%)67(21.5%)M e d i a n14±0.686±3210.5±318±2.114±312±1.213.5±2.214±1.187±22.419±1,086R a n g e3–6910–1,8405–704–3004–1206–525–1046–607–3605–339,000S C C ,n g /m l %p o s i t i v e42(14.1%)0(0%)3(13.6%)10(3.8%)0(0%)0(0%)3(4.8%)8(6.9%)0(0%)27(8.7%)M e d i a n0.8±0.10.5±0.11.1±0.70.6±0.20.6±0.20.6±0.20.8±0.40.6±1.50.4±0.10.7±0.5R a n g e0.1–2260.1–4.90.1–13.40.1–35.30.1–4.10.1–5.70.1–16.60.1–1650.1–1.50.1–114C Y F R A 21-1,n g /m l %p o s i t i v e117(39.3%)23(25.8%)3(13.6%)148(55.8%)4(9.1%)6(13.3%)15(24.2%)50(43.1%)7(30.4%)150(48.1%)M e d i a n6.5±2.35.5±8.93.4±9.814.5±8.82.9±22±2.83.2±6.67.1±2.13.1±6.79.9±27.3R a n g e0.3–3270.9–5400.7–2190.4–1,4000.4–896–1100.2–2440.7–1860.1–1400.3–6,983P S A ,n g /m l %p o s i t i v e0/230(0%)0/81(0%)0/19(0%)0/155(0%)0/28(0%)39(86.7%)1/46(2.2%)0(0%)0/14(0%)1/169(0.6%)M e d i a n1.3±0.21±0.41.6±0.52.2±0.21±0.3140±2210.8±0.91±0.31±1.9R a n g e0.2–260.2–240.3–10.90.2–16.30.1–7.20.1–8,0000.1–400.4–4.30.06–318A F P ,n g /m l %p o s i t i v e0(0%)0(0%)0(0%)3(1.1%)29(65.9%)1(2.2%)2(3.2%)0(0%)5(21.7%)16(5.1%)M e d i a n2±0.22±0.22±0.22±2.4379±3,9732±1.52±5.32±0.43±122±670R a n g e1–321–81–41–3241–133,8001–681–2971–351–2011–187,700O n e o r a n o t h e r +/t o t a l216/298(72.5%)72/89(80.9%)7/22(31.8%)210/265(81.7%)30/44(68.2%)39/45(86.7%)26/62(41.9%)91/116(78.4%)16/23(69.6%)253(81.1%)L o c o r e g i o n a l55/88(62.5%)6/12(50%)2/5(40%)21/41(55.2%)8/16(50%)5/9(55.6%)2/14(14.3%)7/12(58.3%)0/3(0%)–M e t a s t a s e s161/210(76.7%)66/77(85.7%)5/17(29.4%)189/224(86.3%)22/28(78.6%)34/36(94.4%)24/48(50%)84/104(80.8%)16/20(80%)253(81.1%)N S C L C n o n -s m a l l c e l l l u n g c a n c e r ,S C L C S m a l l c e l l l u n g c a n c e r ,H C C h e p a t o c e l l u l a r c e l l c a r c i n o m a ,N E T n e u r o e n d o c r i n e t u m o r ,C U P c a n c e r o f u n k n o w n p r i m a r y s i t eTumor Biol.。