乙醛脱氢酶1a1在早期胰腺癌的表达及意义

目的探讨胰腺癌组织中乙醛脱氢酶1a1(ALDH1a1)的蛋白表达水平与胰腺癌患者临床病理之间的关联。方法通过免疫组化法检测31例胰腺癌组织及其癌旁组织ALDH1a1的蛋白表达,用Kaplan-Meier法分析ALDH1a1表达水平对胰腺癌患者无病生存期的影响。结果胰腺癌组织中ALDH1a1蛋白的阳性程度高于其癌旁正常组织;ALDH1a1蛋白表达高的胰腺癌患者无病生存期短;ALDH1a1蛋白高表达与肿瘤的低分化程度、大肿块相关,与Ki67、胎盘型谷胱甘肽-S-转移酶(GSTπ)、肺耐药相关蛋白(LRP)表达呈正相关。结论检测胰腺癌组织中ALDH1a1的表达具有预测患者预后的价值。     

急性早幼粒细胞白血病患者血浆D-二聚体水平测定

目的探讨急性早幼粒细胞白血病患者血浆D-二聚体水平的变化及其临床意义。方法采用酶联免疫吸附试验双抗体夹心法测定急性早幼粒细胞白血病患者在初发、缓解、复发3个节段内血浆D-二聚体水平,并以健康体检者作为对照。结果初发患者血浆D-二聚体水平高于健康体检者(P<0.05)。缓解患者血浆D-二聚体水平与健康体检者比较差异无统计学意义(P>0.05)。复发患者血浆D-二聚体水平高于健康体检者(P<0.05)。结论急性早幼粒细胞白血病患者体内存在凝血及纤溶功能的异常,易并发弥漫性血管内凝血,监测血浆D-二聚体水平有助于急性早幼粒细胞白血病患者病情变化及预后的判断。     

血浆D-二聚体在卵巢癌患者围手术期监测中的应用价值

背景与目的:卵巢癌患者因肿瘤负荷、手术创伤等原因,凝血系统的平衡状态常被打破,容易出现出血或血栓性疾病。本研究旨在探讨血浆D-二聚体在卵巢癌患者手术前、后监测中的应用价值。方法:测定161例卵巢癌患者和41例卵巢良性肿瘤患者血浆D-二聚体水平,对其中23例卵巢癌患者术后D-二聚体变化进行随访监测。结果:卵巢癌组血浆D-二聚体水平明显高于良性肿瘤组(P<0.01);卵巢癌患者血浆D-二聚体水平随分期增加而明显升高,差异有统计学意义(χ2=78.894,P<0.01),提示卵巢癌患者凝血及纤溶功能障碍随病情发展呈现加重趋势;9例患者术后出现血栓性疾病前,其D-二聚体水平均呈持续高水平或一过性下降后突然升高。结论:监测卵巢癌患者手术前后血浆中D-二聚体浓度,有助于术前筛查血栓高风险人群,预警术后深静脉血栓形成,争取早预防、早诊断、早治疗,改善患者的预后。     

低分子肝素钠对晚期肿瘤的治疗价值

目的：探讨晚期肿瘤患者血浆D-二聚体水平及低分子肝素钠的干预治疗价值。方法：采用胶乳凝集法测定晚期肿瘤患者与健康志愿者的血浆D-二聚体。对血浆D-二聚体水平高于正常的60例晚期肿瘤患者,用低分子肝素钠干预治疗1周以上,观察患者血浆D-二聚体水平的变化,患者血浆D-二聚体水平的变化与疗效和预后的关系。结果：晚期肿瘤患者血浆D-二聚体水平较健康对照组显著升高（ P<0.001）,不同病期与部位的肿瘤血浆D-二聚体水平有统计学差异,重症患者抗凝治疗后血浆D-二聚体水平显著下降。患者生存质量明显提高。血浆D-二聚体水平过高的患者预后差（P<0.05）。结论：低分子肝素钠抗凝治疗能防治晚期肿瘤患者的血栓栓塞性并发症,改善患者生存质量,临床获益明显。     

术前血浆D-二聚体水平与浆液性卵巢癌一线化疗疗效及预后的相关性评价

目的:探讨术前血浆D －二聚体水平与浆液性卵巢癌一线化疗疗效及预后的相关性。方法:回顾性分析天津医科大学肿瘤医院2008年1 月至2010年5 月143 例浆液性卵巢癌患者的术前血浆D-二聚体水平,并依据血浆D-二聚体正常水平分为血浆D-二聚体水平（≤ 0.3 mg/L ）正常组（100 例）和血浆D-二聚体水平（> 0.3 mg/L ）升高组（43例）,比较血浆D-二聚体不同水平与临床病理因素、化疗疗效及预后的相关性。结果:血浆D-二聚体水平与FIGO分期、残余病灶大小、恶性腹水、术前CA125 水平及新辅助化疗密切相关。化疗后血浆D-二聚体水平升高组的完全缓解率34.88%（15/ 43）明显低于血浆D-二聚体正常组73.00%（73/ 100）,两者比较差异具有统计学意义（P < 0.001）。 血浆D-二聚体水平升高组的无进展生存率与总生存率明显低于血浆D-二聚体正常组（25.58% vs . 50.00% 与32.56% vs . 65.00%）,两者比较差异具有统计学意义（P < 0.05）。 Cox 多因素分析显示血浆D －二聚体水平是患者预后的独立预测因素。结论:术前血浆D-二聚体水平可作为有效预测浆液性卵巢癌一线化疗疗效及预后的生物学指标。      

D-二聚体水平与非霍奇金淋巴瘤患者预后关系的研究

  目的  本研究拟探讨D-二聚体升高与非霍奇金淋巴瘤（Non-Hodgkin Lymphoma NHL）患者总生存之间的关系。  方法  回顾性分析2000年1月至2009年12月天津医科大学附属肿瘤医院收治的经病理证实的NHL 425例,分析患者临床病理特征、D-二聚体及国际预后指数（the International prognostic index,IPI）对总生存的影响。  结果  血浆D-二聚体水平与IPI评分明显相关。低、中、高水平D-二聚体组5年生存率分别为97.4%,86.1%,35.0%（P < 0.05）。与IPI为0或1的患者相比,IPI≥4分者预后较差（P < 0.05）。Ann Arbor分期、病理类型、D-二聚体水平以及IPI评分是影响总生存的主要因素,多元分析表明IPI评分、血浆D-二聚体水平是独立预后因子。  结论  高水平的D-二聚体是NHL患者预后差的标志物。      

血浆D-二聚体检验对急性白血病患者病情进展及疗效评估的临床意义

目的探讨血浆D-二聚体检验对急性白血病患者病情进展及疗效评估的临床意义。方法选择180例急性白血病患者作为观察组研究对象,另外选择同期60例健康体检者作为对照组研究对象,应用免疫比浊法检测血浆D-二聚体水平。对初治期(180例)、缓解期(123例)、复发期(38例)患者进行动态监测D-二聚体,并对比分析急性非淋巴细胞白血病(ANLL)与其他类型白血病患者的血浆D-二聚体水平。结果与对照组相比,初治期、复发期急性白血病患者的D-二聚体水平均明显升高(均P<0.05);与缓解期相比,初治期、复发期急性白血病患者D-二聚体水平均明显升高(均P<0.05);对照组缓解期急性白血病患者D-二聚体水平差异无统计学意义(P>0.05);初治期与复发期急性白血病患者D-二聚体水平差异无统计学意义(P>0.05)。与其他类型急性白血病相比,ANLL患者初治期D-二聚体水平明显升高(P<0.05),但缓解期两组D-二聚体水平比较,差异没有统计学意义(P>0.05)。结论血浆D-二聚体可反映急性白血病患者病情变化,动态监测D-二聚体水平有利于病情观察及疗效评估。     

直肠癌患者血浆D-二聚体和纤维蛋白水平的检测及临床价值

目的探讨直肠癌患者血浆D-二聚体(D-dimer)和纤维蛋白原(Fib)水平变化与直肠癌疗效、预后的关系。方法取250例直肠癌患者和40例对照组(健康体检者)的静脉血,应用全自动血凝仪测定,血浆D-二聚体含量采用乳胶凝集半定量法测定,血浆纤维蛋白原含量采用Clauss法测定。结果250例直肠癌患者中,直肠癌初治组、难治转移组、治疗缓解组的血浆D-二聚体和纤维蛋白原水平明显升高,与对照组比较差别有显著性;治疗缓解组的血浆D-二聚体、纤维蛋白原水平较初治组及难治转移组有明显下降。结论血浆D-二聚体和纤维蛋白原水平变化与直肠癌的病情严重程度及预后有明显相关性,可作为直肠癌的辅助诊断及预后判断的一项早期实验室参考指标。     

术前血小板、血浆纤维蛋白原及D-二聚体水平与小细胞肺癌预后的相关性分析

目的:回顾性分析术前血小板（platelet,PLT）、血浆纤维蛋白原（fibrinogen,Fib）及D-二聚体（D-dimer,D-D）水平对小细胞肺癌（SCLC）患者预后的影响。方法:选取2005年1月至2017年12月在中日友好医院初次就诊的57例SCLC患者术前血小板、血浆纤维蛋白原及D-二聚体等指标,所有患者均经组织病理学确诊。采用SPSS 25.0统计软件对相关临床病理因素及生存期进行分析。结果:术前血小板、血浆纤维蛋白原及D-二聚体水平升高的发生率分别为7.0%、31.6%、19.3%,术前血小板和/或血浆纤维蛋白原和/或D-二聚体水平升高的SCLC患者术后生存期有下降趋势。单因素分析提示,卡氏评分（P=0.038）、TNM分期（P=0.001）、淋巴结转移（P=0.049）及术前D-二聚体水平（P=0.003）均与 SCLC预后相关;多因素分析提示,TNM分期（P=0.005）、术前D-二聚体水平（P=0.021）为 SCLC的独立预后因素,TNM分期为Ⅲ期、术前D-二聚体水平升高的SCLC患者预后较差。结论:术前伴有高血凝状态的SCLC患者预后较差,术前D-二聚体水平测定可作为SCLC预后预测的潜在指标,具有一定的临床意义。     

术前血浆D-二聚体水平对食管鳞癌预后判断的价值

目的：探讨术前血浆 D -二聚体水平与食管鳞癌患者预后的关系。方法入组经病理确诊的112例食管鳞癌患者，分析其血浆 D -二聚体水平与临床病理参数、生存情况的关系。结果术前血浆 D -二聚体水平与患者的 T 分期、N 分期及是否复发有关（P <0.05）。血浆 D -二聚体水平升高组患者的1 a、3 a 生存率分别为76.8%、34.1%，低于 D -二聚体正常组的85.5%、52.4%，差异有统计学意义（P 均<0.05）。多因素分析显示血浆 D -二聚体水平升高是一个不良预后因素（HR：1.679，P <0.05）。结论术前高水平血浆 D -二聚体预示食管鳞癌患者较差的预后。     

Doubling time of serum CA 19-9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is generally a disease with a poor prognosis, and relationship between change of serum CA 19-9 level and progression of this disease was investigated with regard to clinical pace of disease and tumor growth. METHODS: CA 19-9 doubling time was examined in 75 patients with pancreatic cancer, including 41 inoperable cases. Then, its relation with their prognosis and change in tumor was evaluated. RESULTS: The doubling time of CA 19-9 and CEA could be calculated in 90.2% and 58.5% of patients with inoperable pancreatic cancer. CA 19-9 doubling time was clearly associated with survival time in inoperable and palliatively operated cases, but not with sex, age, site of the lesion, or liver metastasis, and was significantly correlated with the tumor volume doubling time. CONCLUSIONS: Examination of CA 19-9 doubling time may be useful in clinical evaluation of the prognosis for patients with pancreatic cancer and could possibly prove valuable in terms of the analysis of the growth process in this disease.     

肿瘤标记物CA19-9、CA242对胰腺癌转移和预后预测价值的分析

目的:探讨肿瘤标记物糖类抗原19-9(CA19-9)、糖类抗原242(CA242)对胰腺癌转移和预后的预测价值.方法:选取80例胰腺癌患者和20例健康人群的血清样本,测定血清中CA19-9、CA242水平.探讨两者与胰腺癌临床分期、分型、肿瘤大小、淋巴转移情况和预后的关系.结果:胰腺癌患者血清CA19-9、CA242水平显著高于健康人群(P＜0.01).胰腺癌患者中Ⅲ+ Ⅳ期患者血清CA19-9、CA242水平显著高于Ⅰ+Ⅱ期患者(P＜0.05),淋巴转移患者血清CA19-9、CA242水平显著高于无转移患者(P＜0.05),生存期小于8个月患者血清CA19-9、CA242水平显著高于大于8个月患者(P＜0.05).以CA19-9 37.0U/ml、CA242 20.0U/ml为阳性阈值,以CA19-9阳性且CA242阳性组的正确指数最高.结论:胰腺癌患者血清CA19-9、CA242水平对胰腺癌患者术前诊断和预后分析具有一定参考价值.     

The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer.

AIM: Serum tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA242 were investigated to evaluate the values of single and combined test in the diagnosis and prognosis of pancreatic cancer. METHODS: Pre-operative serum CEA, CA19-9 and CA242 were measured in 105 pancreatic cancers, 70 non-pancreatic malignancies and 30 benign pancreatic diseases. RESULTS: The sensitivity of CA19-9 alone was the highest in pancreatic cancer patients (80%), but the specificity was significantly lower than that of CEA and CA242 (P<0.01). The combination of CEA and CA242 could increase the specificity to 92%. In serum CA242 positive patients, the survival time was remarkably shorter than that of patients with negative result (P<0.01). The survival time in patients with more than two markers positive expression of CEA, CA19-9 and CA242 was obviously shorter than that of only one or no marker positive expression (P<0.05). CONCLUSION: The diagnostic rate of CA19-9 in pancreatic cancer is better than that of CEA and CA242. Combined detection of CEA and CA242 can improve the diagnostic specificity obviously. High levels of serum markers are associated with advanced stage of the disease. Patients with two or three markers positive expression of CEA, CA19-9, and CA242 simultaneously had a shorter survival time.     

血清CA19—9的酶免测定及临床应用

本文用生物素—链霉亲和素酶联免疫吸附试验（BSA）对203例血清CA19－9水平进行定量测定。结果显示，在32例胰腺癌组为826±411U／ml，40例肝癌组为107±46．5U／ml，与76例正常人对照组21．2±9．24U／ml比较均有明显差异（P＜0．05），以胰腺癌组升高最显著。在39例胃癌组为25．4±11．0U／ml，与正常对照组比较均无明显差异（P＞0．05）。27例胰腺癌病人术前为910±452U／ml，术后为187±89．0U／ml，血清CA19－9水平明显下降（P＜0．05）。血清CA19－9水平分析对胰腺癌的鉴别诊断、疗效观察及预后评估有较高价值。     

Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9.

PURPOSE: More accurate serum markers of pancreatic cancer could improve the early detection and prognosis of this deadly disease. We compared the diagnostic utility of a panel of candidate serum markers of pancreatic cancer. EXPERIMENTAL DESIGN: We collected preoperative serum from 50 patients with resectable pancreatic adenocarcinoma, as well as sera from 50 patients with chronic pancreatitis and 50 age/sex-matched healthy controls from our institution. Sera were analyzed for the following candidate markers of pancreatic cancer: CA19-9, macrophage inhibitory cytokine 1 (MIC-1), osteopontin, tissue inhibitor of metalloproteinase 1, and hepatocarcinoma-intestine-pancreas protein levels. RESULTS: By logistic regression analysis, MIC-1 and CA19-9 were significant independent predictors of diagnosis. Receiver operating characteristic curve analysis showed that MIC-1 was significantly better than CA19-9 in differentiating patients with pancreatic cancer from healthy controls (area under the curve is 0.99 and 0.78, respectively; P = 0.003), but not in distinguishing pancreatic cancer from chronic pancreatitis (area under the curve of 0.81 and 0.74, respectively; P = 0.63). Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein, osteopontin, and tissue inhibitor of metalloproteinase 1 serum levels did not provide additional diagnostic power. CONCLUSION: In the differentiation of patients with resectable pancreatic cancer from controls, serum MIC-1 outperforms other markers including CA19-9.     

Evaluation of CA 19-9 as a serum tumour marker in pancreatic cancer

Serum concentrations of the CA 19-9 antigen were determined in 91 patients with pancreatic cancer and in 111 patients with benign pancreatic, biliary and hepatocellular diseases. The CA 19-9 concentration was above the cut-off limit (37 U ml-1) in 78% of the patients with pancreatic cancer and high levels (greater than 500 U ml-1) were seen in 56% of these patients. Elevated levels were also seen in benign diseases (22%), especially in patients with extrahepatic cholestasis (up to 440 U ml-1). Hepatocellular jaundice and pancreatitis were associated with normal values (84% of the patients), or with only slightly elevated CA 19-9 levels (up to 88 U ml-1). The CA 19-9 test can be useful as an additional diagnostic tool for the detection of pancreatic cancer. Preliminary results suggest that the CA 19-9 assay can be used in the monitoring of surgically treated patients.     

The clinical utility of serum CA 19-9 in the diagnosis,prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal

Background

Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management.

Methods

Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer.

Results

Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%).

Conclusions

CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.Key Words : Pancreatic cancer, tumor markers, CA 19-9, diagnosis, screening, prognosis, resectability, recurrence     

CA19-9和CA242发光免疫分析对胰腺癌的诊断意义

目的 :分析肿瘤标志物CA19 9、CA2 4 2结果对胰腺癌的诊断意义。方法 :采用发光免疫分析技术 ,选择 2 0 0 1年 1月 - 2 0 0 2年 12月本院门诊及住院患者共 12 5人进行了CA19 9、CA2 4 2检测 ,其中 13例为临床明确诊断的胰腺癌患者。结果 :胰腺癌患者血清中的CA19 9、CA2 4 2水平明显高于对照组。结论 :CA19 9、CA2 4 2水平分析对胰腺癌的鉴别诊断、疗效观察及预后评估有较高价值     

Serum diagnosis of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass spectrometry.

PURPOSE: Each year in the United States, approximately 30,000 people die from pancreatic cancer. Fewer than 5% of patients survive >5 years after diagnosis, because most patients present with advanced disease. Early diagnosis may improve the prognosis of patients with pancreatic cancer. EXPERIMENTAL DESIGN: In an attempt to improve on current approaches to the serological diagnosis of pancreatic cancer, we analyzed serum samples from patients with and without pancreatic cancer using surface-enhanced laser desorption and ionization (SELDI) protein chip mass spectrometry. Using a case-control study design, serum samples from 60 patients with resectable pancreatic adenocarcinoma were compared with samples from 60 age- and sex-matched patients with nonmalignant pancreatic diseases, as well as 60 age- and sex-matched healthy controls. To increase the number of proteins potentially identifiable, serum was fractionated using anion exchange and profiled on two ProteinChip surfaces (metal affinity capture and weak cation exchange). RESULTS: We determined a minimum set of protein peaks able to discriminate between patient groups and used the unified maximum separability algorithm to compare the performance of the individual marker panels alone or in conjunction with CA19-9. Among the peaks identified by SELDI profiling that had the ability to distinguish between patient groups, the 2 most discriminating protein peaks could differentiate patients with pancreatic cancer from healthy controls with a sensitivity of 78% and specificity of 97%. These 2 markers performed significantly better than the current standard serum marker, CA19-9 (P < 0.05). The diagnostic accuracy of the 2 markers was improved by using them in combination with CA 19-9. Similarly, a combination of 3 SELDI markers and CA19-9 was superior to CA19-9 alone in distinguishing individuals with pancreatic cancer from the combined pancreatic disease controls and healthy subject groups (P = 0.078). SELDI markers were also better than CA19-9 in distinguishing patients with pancreatic cancer from those with pancreatitis. CONCLUSION: SELDI profiling of serum can be used to accurately differentiate patients with pancreatic cancer from those with other pancreatic diseases and from healthy controls.     

Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiochemotherapy

PURPOSE: To determine the predictive value of carbohydrate antigen (CA) 19-9 in pancreatic cancer treated with radiochemotherapy. METHODS AND MATERIALS: Ninety-five patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil and folinic acid. CA 19-9 was measured before therapy, each week during therapy, and every 4 weeks during the follow-up period. RESULTS: The median CA 19-9 before treatment was 420 U/mL; in the responder group it was 117 U/mL, and in the nonresponder group it was 806 U/mL. Patients with a pretreatment CA 19-9 less than the median had not only a significantly better tumor response (45.8%) but also a better survival prognosis (median survival 12.3 months) than those with a level higher than the median (tumor response 12.8%; median survival 7.1 months). The posttreatment median CA 19-9 for all patients also exhibited prognostic significance. The median survival of patients with a CA 19-9 level lower than the posttreatment median of 293 U/mL was 13.5 months, compared with 7.2 months for those with a CA 19-9 level greater than the median. To detect recurrent disease during follow-up, the sensitivity of CA 19-9 was 100% and the specificity 88%. CONCLUSION: Our results indicate that CA 19-9 is of predictive value for prognosis, response, and detecting recurrence of pancreatic cancer in patients undergoing combined radiochemotherapy. Therefore, we recommend the routine implementation of CA 19-9 observation during the clinical course of treatment for patients with pancreatic cancer undergoing radiochemotherapy.