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.     

Prognostic value of preoperative serum tumor markers in gastric cancer

AIM: To evaluate the prognostic value of preoperative carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and CA50 in patients undergoing D2 resection.METHODS: We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9, and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses.RESULTS: The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and 24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age (P < 0.001), sex (P = 0.022), tumor size (P = 0.007) and depth of invasion (P = 0.018); CA19-9 with tumor size (P = 0.042) and lymph node metastasis (P < 0.001); and CA50 only with lymph node metastasis (P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy (P = 0.027).CONCLUSION: Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy.     

Carbohydrate Antigen 19-9 Levels Associated with Pathological Responses to Preoperative Chemoradiotherapy in Rectal Cancer

Purpose: To investigate whether pretreatment serum carbohydrate antigen 19-9 (CA 19-9) levels are associated with pathological responses to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Materials and Methods: In total, 260 patients with locally advanced rectal cancer (cT3-4NanyM0) whounderwent preoperative CRT and radical surgery were analyzed retrospectively. CRT consisted of 50.4 Gy pelvic radiotherapy and concurrent chemotherapy. Radical surgery was performed at a median of 7 weeks after CRT completion. Pathological CRT response criteria included downstaging (ypStage 0-I) and ypT0-1. A discrimination threshold of CA 19-9 level was determined using a receiver operating characteristics analysis. Results: The median CA 19-9 level was 8.0 (1.0-648.0) U/mL. Downstaging occurred in 94 (36.2%) patients andypT0-1 in 50 (19.2%). The calculated optimal threshold CA 19-9 level was 10.2 U/mL for downstaging and 9.0 U/mL for ypT0-1. On multivariate analysis, CA 19-9 (≤ 9.0 U/mL) was significantly associated with downstaging (odds ratio, 2.089; 95% confidence interval, 1.189-3.669; P=0.010) or ypT0-1 (OR, 2.207; 95%CI, 1.079-4.512; P=0.030), independent of clinical stage or carcinoembryonic antigen. Conclusions: This study firstly showed a significant association of pretreatment serum CA 19-9 levels with pathological CRT responses of rectal cancer. The CA 19-9 level is suggested to be valuable in predicting CRT responses of rectal cancer cases before treatment.     

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.     

Prognostic relevance of carbohydrate antigen 19-9 levels in patients with advanced biliary tract cancer.

Serum carbohydrate antigen 19-9 (CA 19-9) has been identified as biochemical marker for biliary tract cancer (BTC). The purpose of this study was to evaluate its value as a treatment response marker and its value as a prognostic parameter in patients with unresectable BTC. We analyzed 70 patients with BTC treated with chemotherapy. CA 19-9 levels before and after two treatment courses were analyzed with respect to their effect on treatment response. Patients were categorized into two subgroups according to biliary stenting: patients without endoscopic intervention or biliary drainage (non-stent subgroup) and patients with endoluminal stenting (stent subgroup). Pretreatment CA 19-9 levels were prognostic with respect to overall survival for the entire study population. Patients with CA 19-9 levels above the median of 300 units/mL had a nearly 3-fold risk for early death (hazard ratio, 2.92; 95% confidence interval, 1.51-5.64; adjusted P = 0.002) as compared with patients with CA 19-9 levels 相似文献   

血清CA19-9预测吉西他滨化疗的晚期胰腺癌患者的预后

目的:将晚期胰腺癌化疗前后血清癌抗原19-9(CA19-9)变化水平与其影像学客观反应和临床受益反应进行比较,以探讨与预后关系最密切的因素。方法:比较血清CA19-9下降水平与影像学客观反应和临床受益反应作为判定晚期胰腺癌患者接受吉西他滨单药或以其为基础的联合方案化疗后生存期的差异。结果:所有64例患者的中位生存期(median survival time,MST)为7.0个月。血清CA19-9基线水平小于中位值(928.6ng/ml)患者的生存期明显长于其水平大于中位值者(9.4个月vs 4.2个月,P<0.001)血清CA19-9下降水平与MST和疾病无进展(non-progression disease,NPD)及临床受益反应(clinical benefit response,CBR)密切相关,化疗2周期后血清CA19-9下降水平≥25%的MST明显长于其水平下降<25%者(8.9个月vs 4.4个月,P<0.001)。影像学疾病无进展(NPD)和临床受益(CBR)均与MST密切相关,NPD患者的MST明显长于疾病进展者(8.8个月vs 7.4个月,P=0.022);CBR患者的MST明显长于非CBR者(9.1个月vs 6.2个月,P=0.022)。多因素分析显示,血清CA19-9基线水平的中位值和血清CA19-9下降水平≥25%是影响预后的独立因素生存期密切相关,而NPD和CBR与预后无关。结论:与影像学客观反应和临床受益反应相比,血清CA19-9下降水平能更有力地预测预后生存期。血清CA19-9下降水平是指导临床治疗晚期胰腺癌较合理的指标。     

术前预后营养指数在肝内胆管癌根治性切除术后的预后预测价值

目的:探讨术前预后营养指数（prognostic nutritional index,PNI）在肝内胆管癌根治性切除术后的预后预测价值。方法:回顾性分析2012年1月至2018年12月于我院普通外科因肝内胆管癌行根治性切除术的107例患者的临床病理资料,分析PNI与患者临床病理特征、预后预测价值及其与预后的关系。结果:术前低PNI组与高PNI组患者的临床病理特征分析显示:低PNI组患者中CEA>5.0 ng/mL、CA19-9>39.0 U/mL、Child-Pugh肝功分级呈B级、肿瘤大小>5 cm、T分期呈T3及T4期、N1期比例明显高于高PNI组患者（P＜0.05）。单因素分析显示,PNI是影响患者预后的危险因素（P＜0.05）。多因素分析显示,PNI是影响患者预后的独立危险因素(P＜0.05)。时间依赖的ROC曲线显示:PNI在预测患者术后的1年、3年及5年总体生存期的AUC分别为67.93%、70.44%及68.32%。对独立危险因素分层分析发现:CEA≤5.0 ng/mL、CA19-9≤39.0 U/mL、CA19-9>39.0 U/mL及N0患者中低PNI组和高PNI组总体生存时间具有统计学差异（P＜0.05）。结论:术前PNI是肝内胆管癌根治性切除术后的独立危险因素,可用于患者预后预测。术前PNI对于CEA≤5.0 ng/mL、CA19-9≤39.0 U/mL、CA19-9>39.0 U/mL及N0者具有更好的预后预测价值。     

淋巴结转移对肝内胆管细胞癌患者预后的影响及临床相关因素研究

背景与目的：肝内胆管细胞癌（intrahepatic cholangiocarcinoma,ICC）是原发性肝癌中第二常见的病理学类型,起病隐匿,预后不佳。ICC常出现淋巴结转移（lymph node metastasis,LNM）。探讨肝十二指肠LNM与ICC患者临床相关因素及预后的关系。方法：共招募322例ICC患者在复旦大学附属中山医院行根治性肝肿瘤切除术,分析肝十二指肠LNM与临床病理学特征的关系及预后价值。结果：LNM与乙型肝炎病毒（hepatitis B virus,HBV）阳性、血清CA19-9>89 U/mL、肿瘤数目、肿瘤直径（>5 cm）、微血管侵犯、TNM分期、中性粒细胞/淋巴细胞比值（neutrophil-to-lymphocyte ratio,NLR）显著相关。Kaplan-Meier分析显示,无LNM的ICC患者组的1、3和5年总生存率（overall survival,OS）分别为80.8%、53.4%和40.3%,显著高于伴有LNM组（47.4%、20.4%和10.2%,P<0.001）。无LNM的ICC患者组的1、3和5年无瘤生存率（recurrence-free survival,RFS）分别为62.6%、43.4%和36.3%,显著高于伴有LNM组（25.6%、16.6%和12.4%,P<0.001）。进一步研究发现,血清CA19-9>89 U/mL（P<0.001）、肿瘤直径>5 cm（P=0.042）、肿瘤数目（P<0.001）、微血管侵犯（P=0.022）、TNM分期（P<0.001）、NLR≥2.49（P=0.016）、淋巴细胞/单核细胞比值（lymphocyte-to-monocyte ratio,LMR）<4.45（P=0.048）及LNM（P<0.001）与ICC患者术后无瘤生存时间（time to recurrence,TTR）显著相关;血清CA19-9>89 U/mL（P<0.001）、肿瘤直径>5 cm（P=0.008）、肿瘤数目（P=0.002）、TNM分期（P<0.001）、NLR≥2.49（P<0.001）、LMR<4.45（P=0.002）及LNM（P<0.001）与ICC患者术后OS显著相关。多因素分析显示,血清CA19-9>89 U/mL、肿瘤数目、LNM是影响ICC患者术后TTR的独立预后因素;血清CA19-9>89 U/mL、肿瘤数目、LMR<4.45、LNM是影响ICC患者术后OS的独立预后因素。结论：肝十二指肠LNM是ICC患者术后的独立预后因素,准确判断LNM状态具有重要的临床意义。     

血清CA19-9预测吉西他滨化疗的晚期胰腺癌患者的预后

目的：将晚期胰腺癌化疗前后血清癌抗原19-9（CA19-9）变化水平与其影像学客观反应和临床受益反应进行比较,以探讨与预后关系最密切的因素。方法：比较血清CA19-9下降水平与影像学客观反应和临床受益反应作为判定晚期胰腺癌患者接受吉西他滨单药或以其为基础的联合方案化疗后生存期的差异。结果：所有64例患者的中位生存期（median survival time,MST）为7.0个月。血清CA19-9基线水平小于中位值（928.6ng/ml）患者的生存期明显长于其水平大于中位值者（9.4个月vs 4.2个月,P〈0.001）血清CA19-9下降水平与MST和疾病无进展（non-progression disease,NPD）及临床受益反应（clinical benefit response,CBR）密切相关,化疗2周期后血清CA19-9下降水平≥25%的MST明显长于其水平下降〈25%者（8.9个月vs 4.4个月,P〈0.001）。影像学疾病无进展（NPD）和临床受益（CBR）均与MST密切相关,NPD患者的MST明显长于疾病进展者（8.8个月vs 7.4个月,P=0.022）;CBR患者的MST明显长于非CBR者（9.1个月vs 6.2个月,P=0.022）。多因素分析显示,血清CA19-9基线水平的中位值和血清CA19-9下降水平≥25%是影响预后的独立因素生存期密切相关,而NPD和CBR与预后无关。结论：与影像学客观反应和临床受益反应相比,血清CA19-9下降水平能更有力地预测预后生存期。血清CA19-9下降水平是指导临床治疗晚期胰腺癌较合理的指标。     

肝动脉灌注化疗与肝动脉灌注化疗栓塞术治疗IIb-IIIa期肝细胞癌的近远期疗效比较

目的:基于倾向性评分匹配法比较肝动脉灌注化疗术（HAIC）与肝动脉灌注化疗栓塞术(TACE)治疗IIb-IIIa期肝细胞癌近远期疗效。方法:纳入2019年1月-2020年6月在我院就诊的123例肝细胞癌患者作为研究对象,临床分期为IIb-IIIa期,按不同治疗方案将所有患者分为HAIC组和TACE组,采用 1∶1倾向性评分匹配法将两组中倾向性评分最相近的患者进行配对,比较匹配后两组患者治疗前后肝功能和血清肿瘤标志物,治疗后不良反应以及近期疗效,绘制Kaplan-Meier生存曲线,log-tank检验比较匹配后两组患者治疗后2年疾病无进展生存率,Cox回归分析获得影响患者治疗后2年疾病进展的独立预测因素,重点分析不同治疗方法与患者治疗后2年疾病进展的相关性。结果:两组共成功匹配35对患者,匹配后两组年龄、病因、体力状况评分(EGOC评分)、性别、体质量指数、肝硬化、Child-Pugh分级、临床分期、肿瘤最大直径以及肿瘤数目均衡性均有明显提高,匹配后治疗后两组谷丙转氨酶(AST)、谷草转氨酶(ALT)、总胆红素较治疗前明显上升,甲胎蛋白(AFP)较治疗前明显下降(P＜0.05),并且治疗后HAIC组AST、ALT、总胆红素以及AFP明显低于TACE组(P＜0.05)。匹配后HAIC组肝功能损害比例明显低于TACE组(P＜0.05),匹配后两组均无患者达到完全缓解(CR),HAIC组部分缓解(PR)患者比例明显高于TACE组(P＜0.05),匹配后HAIC组患者治疗后2年疾病无进展生存率高于TACE组(57.1% vs 31.1%,P＜0.05),多因素Cox回归分析结果显示,临床分期、AFP、治疗方法为影响患者治疗后2年疾病进展的独立预测因素(P＜0.05)。结论:相较于TACE治疗,HAIC治疗对IIb-IIIa期肝细胞癌患者的肝功能损害程度更低,安全性更高,近期疾病控制率和远期疾病无进展生存率更高。     

血清miR-135及miR-601在胃癌患者中的表达及其诊断价值

背景与目的：胃癌是消化内科常见的恶性肿瘤。探讨血清miR-135及miR-601在胃癌患者中的表达及其诊断价值。方法：选取2016年1月1日—2019年9月30日三亚中心医院收治的胃癌患者152例,根据胃癌病情进展及临床病理学分期分为早期胃癌组（n=62）和进展期胃癌组（n=90）,Ⅰ～Ⅱ期（n=65）和Ⅲ～Ⅳ期（n=87）,无淋巴结转移组（n=73）和淋巴结转移组（n=79）。另选择96例非胃癌患者作为非胃癌组,60例健康体检正常者作为对照组。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR）检测各组血清miR-135及miR-601表达水平,化学发光法测定糖类抗原72-4（carbohydrate antigen 72-4,CA72-4）及糖类抗原19-9（carbohydrate antigen 19-9,CA19-9）水平,分析其对早期胃癌的诊断价值。采用Pearson相关分析来分析胃癌患者血清miR-135、miR-601水平与CA72-4及CA19-9的相关性。结果：与非胃癌组和对照组比较,胃癌组血清miR-135、miR-601、CA72-4及CA19-9水平均明显升高（P均<0.001）。进展期胃癌组血清miR-135（5.70±1.84 vs 3.83±1.12）、miR-601（11.28±3.73 vs 7.36±2.15）、CA72-4［（41.75±10.14）U/mL vs（17.82±4.93）U/mL］及CA19-9［（63.72±17.50）U/mL vs （35.84±10.36）U/mL］水平均明显高于早期胃癌组（均P<0.001）。Ⅲ～Ⅳ期胃癌患者血清miR-135（6.10±1.90 vs 3.74±1.08）、miR-601（12.14±3.92 vs 7.05±2.04）、CA72-4［（44.68±12.35）U/mL vs（16.40±4.52）U/mL］和CA19-9［（68.53±19.13）U/mL vs（33.75±10.60）U/mL］水平均明显高于Ⅰ～Ⅱ期（均P<0.001）,而且Ⅱ期胃癌患者血清miR-135、miR-601、CA72-4及CA19-9水平均明显高于对照组（P<0.05）。淋巴结转移组血清miR-135（6.24±1.95 vs 3.65±0.97）、miR-601（12.60±4.13 vs 6.84±1.92）、CA72-4［（48.70±12.37）U/mL vs （14.85±4.20）U/mL］和CA19-9［（72.36±20.25）U/mL vs（31.60±10.17）U/mL］水平均明显高于无淋巴结转移组（均P<0.001）。受试者工作特征（receiver operating characteristic,ROC）曲线分析结果显示,血清miR-135、miR-601、CA72-4及CA19-9水平诊断早期胃癌的最佳截断值分别为3.78、7.14、17.63 U/mL、35.70 U/mL,四项联合诊断早期胃癌的 曲线下面积（area under curve,AUC）（0.920,95% CI：0.860～0.978）最大,其灵敏度和特异度分别为98.6%和77.4%。相关分析显示,胃癌患者血清miR-135、miR-601水平与CA72-4及CA19-9均呈正相关（r=0.748,P<0.001,r=0.694,P<0.001;r=0.815,P<0.001;r=0.716,P<0.001）。结论：胃癌患者血清miR-135、miR-601、CA72-4及CA19-9水平明显升高,四项联合检测有助于提高早期胃癌的诊断价值。     

Serum CA19-9 response as a surrogate for clinical outcome in patients receiving fixed-dose rate gemcitabine for advanced pancreatic cancer

The use of serial serum measurements of the carbohydrate antigen 19-9 (CA19-9) to guide treatment decisions and serve as a surrogate end point in clinical trial design requires further validation. We investigated whether CA19-9 decline represents an accurate surrogate for survival and time to treatment failure (TTF) in a cohort of 76 patients with advanced pancreatic cancer receiving fixed-dose rate gemcitabine in three separate studies. Statistically significant correlations between percentage CA19-9 decline and both overall survival and TTF were found, with median survival ranging from 12.0 months for patients with the greatest degree of biomarker decline (> 75%) compared with 4.3 months in those whose CA19-9 did not decline during therapy (P < 0.001). Using specific thresholds, patients with > or = 25% decline in CA19-9 during treatment had significantly better outcomes than those who did not (median survival and TTF of 9.6 and 4.6 months vs 4.4 and 1.5 months; P < 0.001). Similar results were seen using both 50 and 75% as cutoff points. We conclude that serial CA19-9 measurements correlate well with clinical outcomes in this patient population, and that decline in this biomarker should be entertained for possible use as a surrogate end point in clinical trials for the selection of new treatments in this disease.     

Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer

Purpose

RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 in patients with resectable pancreatic carcinoma following surgery. Our study aimed to investigate whether CA 19-9 provided similar prognostic information in patients with locally advanced unresectable pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT) and to determine whether such endpoints should therefore be reported in future randomized trials.

Methods and materials

Between December 1998 and October 2009, 253 patients with LAPC were treated with 5-fluourouracil-based concurrent CRT at our institution. Median radiation dose was 50.4 Gy. Only patients with a bilirubin of less than 2 mg/dL at the time the CA 19-9 was evaluated were included in the analysis to avoid the confounding effect of hyperbilirubinemia. Of the eligible patients, 54 had pre and post CRT CA 19-9 values available. The median age was 68 years and 52% were female. Categorized versions of the first post-CRT CA 19-9 were tested in 50 point increments beginning at <50 to >1,000 and percent change in pre to post-CRT CA 19-9 using cut points of 10% increments from <0% (increased) to >90%. Survival was measured from the date of first post CRT CA 19-9 level until death or last follow-up. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for overall survival.

Results

Median CA 19-9 prior to CRT was 363 U/mL and post CRT median was 85.5 U/mL. Following CRT, patients with a decrease of >90% from their baseline CA 19-9 level had a significantly improved median survival than those that did not (16.2 vs. 7.5 months, P=0.01). The median survival of patients with a CA 19-9 level lower than the median post CRT value was 10.3 months, compared with 7.1 months for those with a CA 19-9 level greater than the median (P=0.03). Post CRT CA 19-9 less than 50 U/mL and histologic grade I-II also showed prognostic significance (both P=0.03). In multivariate analysis, post CRT CA 19-9 less than the median level of 85.5 U/mL was an independent prognostic factor for overall survival (HR 0.34; 95% CI, 0.13-0.85, P=0.02).

Conclusions

Our results indicate that post treatment CA 19-9 is predictive for overall survival in patient with LAPC following CRT. We recommend that pre and post treatment CA 19-9 levels be obtained in patients receiving CRT and that these values be considered for prognostic nomograms and future clinical trials.Key Words: CA19-9, pancreatic cancer, chemoradiotherapy (CRT)     

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     

A preoperative serum signature of CEA+/CA125+/CA19‐9 ≥ 1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high‐volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19‐9 independently indicated surgical response in pancreatic cancer. Patients with CA19‐9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19‐9 levels decreased postoperatively. CEA and CA125 in the presence of CA19‐9 ≥1000 U/mL could independently predict the non‐decrease of CA19‐9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA⁺/CA125⁺/CA19‐9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy.     

Clinical significance of elevation of serum CA125 level in patients with metastatic bladder carcinoma

Objective: To explore the clinical significance of the examination of serum CA125 level of patients with metastatic bladder carcinoma.Methods: Electrochemiluminescance technique was used to examine the serum CA125 concentration of 58 cases with metastatic bladder cancer.30 cases of superficial bladder cancer and 8 cases of other urological diseases were collected as the control group.Results: Serum CA125 level in 39 (67.2%) out of 58 cases ranged from 36.7 U/mL to 1485.6 U/mL (mean 498.3 U/mL), being higher than normal (＜35 U/mL).Serum CA125 level of metastatic bladder cancer patientswas 324.5 U/mL, significantly higher than that in control group (P＜0.001).Serum CA125 level of 10 patients after transurethral resection operation was significantly lower than that before operation (P＜0.05).Serum CA125 level of 16 patients whorefused further treatment significantly increased from 450.4 U/mL, to 505.8 U/mL (P = 0.041) 3 months after discharge from the hospital.Serum CA125 level of 17 patients significantly decreased from 475.8 U/L to 237.9 U/mL (P＜0.001 ) after bilaterallilac-arterial embolism treatment.Conclusion: CA125 may be a valuable marker for the judgment of advanced metastatic bladder cancer.     

Serum carbohydrate antigen 19-9 and prognosis of patients with gastric cancer

Previous studies have assessed the prognostic role of serum carbohydrate antigen 19-9 (CA 19-9) concentration in patients with gastric cancer, but the findings from those studies were inconsistent. We searched the PubMed and Web of Science databases to find eligible studies assessing the prognostic role of CA 19-9 in patients with gastric cancer. Twelve studies with a total of 5,072 gastric cancer patients were finally included into the meta-analysis. The pooled hazard ratio (HR) with corresponding 95 % confidence interval (95 % CI) for overall survival were calculated to assess the prognostic role of CA 19-9 in patients with gastric cancer. Overall, elevated serum concentration of CA 19-9 (>37 U/mL) was associated with poorer overall survival in patients with gastric cancer (fixed-effects HR?=?1.36, 95 % CI 1.24–1.48, P?<?0.001). Subgroup analysis by study design further showed that elevated serum concentration of CA 19-9 was associated with poorer overall survival in patients with gastric cancer. There was no obvious risk of publication bias. Elevated concentration of serum CA 19-9 is associated with poorer overall survival in patients with gastric cancer.     

High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study

Vascular endothelial growth factor (VEGF) is an important mediator of tumor angiogenesis. A high serum VEGF level has been shown to predict poor response to chemotherapy and poor survival in several cancers, but its prognostic value in hepatocellular carcinoma (HCC) remains unknown. We conducted a prospective study to evaluate the prognostic significance of pretreatment serum VEGF levels on tumor response to treatment and survival of patients with HCC undergoing transarterial chemoembolization (TACE). Pretreatment serum VEGF levels were measured by an enzyme-linked immunosorbent assay in 80 patients with inoperable HCC undergoing TACE. Serum VEGF levels were correlated with clinical data, tumor response to TACE and survival results. The median serum VEGF level was 240 pg/ml (range 9-1730). Serum VEGF levels were positively correlated with the presence of venous tumor thrombus (P=0.011). Pretreatment serum VEGF levels were significantly higher in patients with progressive disease (median 434 pg/ml) than those with stable (median 176 pg/ml, P=0.010) or responsive disease (median 142 pg/ml, P<0.001) after TACE. Patients with serum VEGF >240 pg/ml had significantly worse survival than those with serum VEGF <240 pg/ml (median survival 6.8 vs. 19.2 months, P=0.007). In a Cox multivariate analysis, serum VEGF >240 pg/ml was an independent prognostic factor of survival. In conclusion, the results of this study suggest that serum VEGF level may be useful as a novel prognostic predictor of tumor response and survival of patients with inoperable HCC undergoing TACE treatment.     

可切除肝门部胆管癌患者临床病理特征及预后影响因素分析

目的:探讨可切除肝门部胆管癌（hilar cholangiocarcinoma,HC）患者术前血清CEA、CA19-9水平与临床病理因素的相关性,并进一步分析上述各因素与HC患者行根治术后预后的相关性。方法:回顾性分析2012年1月至2018年1月中国医科大学附属盛京医院收治的109例行根治性切除的HC患者的临床病理资料,研究术前血清CEA、CA19-9水平与各临床病理特征的相关性,并进一步分析上述各因素与HC患者行根治性切除术后预后的相关性。结果:术前血清CEA水平与HC各临床病理特征无关（P＞0.05）。术前黄疸越重,血清CA19-9水平越高（P＜0.05）。肿瘤侵犯血管的HC患者,术前血清CA19-9水平较高（P＜0.05）。HC患者TNM分期越晚,术前血清CA19-9水平越高（P＜0.05）。门静脉侵犯、淋巴结转移、TNM分期以及术前血清CA19-9水平是影响HC患者术后1年生存率的危险因素（P＜0.05）,其中淋巴结转移、门静脉侵犯、CA19-9是影响患者术后1年生存率的独立危险因素（P＜0.05）。结论:可切除HC患者术前血清CA19-9水平与临床分期及血管侵犯情况存在一定相关性;早期 HC患者行根治性切除术后预后较好,提高HC早期诊断率有助于进一步改善HC患者的生存预后;结合术前血清CA19-9水平、门静脉侵犯及淋巴结转移等多种因素可预测HC患者行根治性切除术后的生存率。     

术前血清CA19-9水平对胃癌患者生存预后的影响

  目的   探讨胃癌患者术前检测血清CA19-9的必要性及其对患者预后评估的意义。   方法   收集2003年1月至2008年10月间天津医科大学肿瘤医院收治的513例术前检测血清CA19-9的胃癌患者的临床病理资料，分析CA19-9水平与临床病理因素的关系及其与预后的关系。   结果   513例患者中CA19-9升高者86例（16.8%），CA19-9升高与高龄、大体分型（BorrmannⅢ、Ⅳ型）、组织学类型（低分化、未分化）及浸润深度相关。CA19-9正常（< 39 U/mL）和升高（≥39 U/mL）患者5年生存率分别为45.7%和25.6%，差异有统计学意义（P < 0.001）。分层分析显示，CA19-9水平仅与TNM Ⅲ期患者预后相关（P=0.001）。多因素预后分析证实，CA19-9升高是影响胃癌患者根治术后生存的独立危险因素（HR=1.47，P=0.008）。   结论   术前检测血清CA19-9可为胃癌患者预后评估提供信息，CA19-9升高可能是胃癌根治术后影响患者预后的独立危险因素。