CA19-9 antigen levels can distinguish between benign and malignant pancreaticobiliary disease

BACKGROUND:CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia.However,it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction,and in other non-hepato-pancreatico-biliary conditions.This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease.METHODS:All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included.For malignant disease,a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate.The patients were divided into 4 categories:pancreatic adenocarcinoma(PCa);cholangiocarcinoma(CCa);chronic pancreatitis(CP)and biliary calculous disease(Calc).Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted.RESULTS:Final diagnoses were made of pancreatic adenocarcinoma(PCa,n=73),cholangiocarcinoma(CCa,n=19),ampullary carcinoma(Amp,n=7),neuroendocrine carcinoma(Neu,n=4),duodenal carcinoma(Duo,n=3),chronic pancreatitis(CP,n=115),and biliary calculous disease(Calc,n=27).Median CA19-9 levels(U/ml)were:PCa,653;CCa,408;Duo,403;Calc,27;CP,19;Neu,10.5;Amp,8(reference range:0-37).The CA19-9 levels were significantly greater for malignant than for benign disease,could differentiate PCa from CCa/Duo,and were significantly higher in unresectable than in resectable PCa.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)for CA19-9 were 84.9%,69.7%,67.7%and 86.1%,respectively.A ROC analysis provided an area under the curve for CA19-9 of 0.871(0.820-0.922),giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology.Using this cut-off,the sensitivity was 82.1%,while specificity,PPV and NPV improved to 85.9%,81.3%and 86.5%,respectively.When standard radiology was included(US/ CT/MRCP)in the decision process,the results improved to 97.2%,88.7%,86.6%,and 97.7%.For benign disease,the CA19-9 correlated directly with the serum bilirubin,but for malignant disease,CA19-9 levels were elevated independent of the bilirubin level.CONCLUSIONS:CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology,the diagnostic yield is improved significantly,thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.

Utility of endoscopic ultrasound, cytology and fluid carcinoembryonic antigen and CA 19-9 levels in pancreatic cystic lesions

AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions. METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/ pre-malignant (mucinous cystic neoplasm). Receiver- operator characteristics (ROC) curve analysis was performed. RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%) had benign lesions and 18 (44%) had malignant/pre- malignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffswere 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL) and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL). Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs. CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions.

Pancreatic Cancer with Normal CA 19-9 and Lewis Antigen Negative--Case Report

Pancreatic cancer is an aggressive and lethal disease that affects especially older population. Its more relevant tumor marker is CA 19-9 （carbohydrate antigen 19-9）, although it can be elevated in others clinical situations, like cholangitis and cholestasis. Otherwise, a small people subset, like our patient, do not produce this tumor marker, as on blood as in the tumor, because they are incapable to express the Lewis Antigen. Therefore, this case report is about a patient without Lewis Antigen express and CA 19-9 low levels. We will report a rapid disease progression, despite of low CA 19-9, comparing with available data that often show better prognosis in this setting. Conclusion： Low levels of CA 19-9 do not predict good response or better prognosis in patients that do not express Lewis Antigen.

血清CA19-9CLIA法检测的临床应用

目的探讨血清CA19-9化学发光免疫分析(CLIA)检测的临床应用价值。方法回顾分析1243例患者(其中恶性肿瘤511例、非肿瘤疾病732例)与253例健康对照组的血清CA19-9CLIA法检测水平。结果恶性肿瘤中,胰腺癌、胆囊及胆管癌、结直肠癌、胃癌、肝癌、肺癌、乳腺癌等患者血清CA19-9均值及阳性率均显著高于正常对照组(P<0.01);非肿瘤疾病中,胰腺炎、胆囊及胆管疾病、肝硬化等患者血清CA19-9均值及阳性率显著高于正常对照组(P<0.01);胃肠道疾病、肝炎、肺炎、乳腺非肿瘤疾病等患者血清CA19-9均值及阳性率与正常对照组差异均无显著性(P>0.05)。胰腺癌组、胆囊及胆管癌组、结直肠癌组、胃癌组、肺癌组、乳腺癌组CA19-9均值及阳性率分别显著高于其相对应非肿瘤疾病组(P<0.01)。肝癌组均值及阳性率均显著高于肝硬化组及肝炎组(P<0.01),肝硬化组均值及阳性率均显著高于肝炎组(P<0.01)。结论血清CA19-9CLIA法检测可作为速检项目为临床鉴别诊断胰腺癌、胆囊及胆管癌、结直肠癌、胃癌、肝癌、肺癌、乳腺癌等恶性肿瘤及胰腺炎、胆囊及胆管非肿瘤疾病、肝硬化等疾病提供快速可靠的依据。

The prognostic value of preoperative serum levels of CEA,CA19-9 and CA72-4 in patients with colorectal cancer

INTRODUCTIONCarcinoembryonic antigen ( CEA) , originally described by Gold and Freedman [1] in 1965, is now an acknowledged member of immunoglobulin superfamily[2],with a role as an intracellular adhesion molecule[3].Carbohydrate antigen 19-9(CA19-9), obtained with a monoclonal antibody produced by immunizing a monoclonal antibody produced by immunizing a mouse with a colonic cancer cell line in 1979[4],is a ligand for E-selectin that plays an important role in the addhesion of cancer cells to endothelial cells [5,6].

Tumor biomarkers： help or mislead in the diagnosis of xanthogranulomatous cholecystitis？-analysis of serum CA 19-9,carcinoembryonic antigen, and CA 12-5

Background Xanthogranulomatous cholecystitis （XGC） is a rare type of gallbladder inflammation.Unlike other cholecystitis,it can be easily misdiagnosed as gallbladder cancer based on radiological images.In response to misdiagnosis,extended surgical treatments are inappropriately given to patients,which is not beneficial to their health and/or recovery.In this study,we set out to determine whether tumor biomarkers can help to avoid misdiagnosis in patients with XGC.Methods Between January 2005 and January 2012,a total of 37 preoperative patients at Sir Run Run Shaw Hospital were suspicious of having gallbladder cancer and was pathologically confirmed to be XGC after surgical operations.Before operations,all patients received a tumor biomarker test to verify diagnosis,which included serum CA 19-9,carcinoembryonic antigen （CEA）,and CA 12-5.Results A measured amount （54.05％） of cases （20 in 37） had at least one elevation over the thresholds of CA 19-9 （37 IU/L）,CEA （5 ng/ml）,and CA 12-5 （35 IU/L）,which increased the suspicion of malignancy and consequently enhanced the difficulty to make right diagnosis of XGC as benign.45.95％ of cases （17 in 37） had an elevation in CA 19-9.2.70％of cases （one in 37） had an elevation in CEA and 24.32％ of cases （nine in 37） had an elevation in CA 12-5.Analysis with Fisher＇s exact test discovered that the presence of common bile duct stone was a contributor to elevations of CA19-9 in patients with XGC.However,even in cases without common bile duct stones,42.86％ of patients （nine in 21） had elevations of at least one tumor biomarker.Among them,26.09％ of patients （six in 21） had elevations of CA 19-9,with the maximum of 536.29 IU/L.Conclusions The elevations of tumor biomarkers in XGC were frequent,suggesting their inabilities to clarify the disease＇s nature,especially when there was a suspicion of gallbladder cancer.Intraoperative frozen pathology of gallbladder might be a possible solution.However,it is against the en bloc surgical principle and has the potential to cause tumor cell spreading.More research should be conducted,such as the discovery of a novel biomarker,so that XGC can less likely be misdiagnosed as malignancy until the final pathological judgment.

Blood group type antigens in pancreatic intraductal papillary mucinous neoplasms

BACKGROUND: There are few data on blood group(BG) types and types of pancreatic cancers. The aims of this study were to study BG types and BG-antigens in pancreatic intraductal papillary mucinous neoplasms(IPMNs). METHODS: BG type and tumor BG-antigen(glycoprotein) expression(studied by immunohistochemistry on tissue microarrays) were analyzed with regard to characteristics of 101 surgically resected pancreatic IPMNs. RESULTS: Non-O BG type predicted invasive carcinoma independently from high serum CA19-9 and male gender. BG type A was observed more frequently in women than in men. Chronic pancreatitis was more frequently seen in patients with BG type B or AB. Aberrant tumor expression(with regard to BG type) of loss of A antigen expression type occurred in 15.0% of IPMNs and of loss of B antigen expression type in 62.5% of IPMNs. Intraneoplasm BG-antigen expression was not related to dysplasia grade or invasion. CONCLUSION: The results of the study suggest that in pancreatic IPMN, non-O BG type predicted invasive carcinoma, whereas for intratumor BG-antigen expression no specific patterns were detected with regard to the progression of glandular epithelial dysplasia or invasion.

Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

AIM To determine the association of p53, carcinoembryonic antigen(CEA) and CA19-9 protein expression with esophageal carcinogenesis.METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia(BCH), 247 with low-grade dysplasia(LGD), 51 with high-grade dysplasia(HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROCcurve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma

Background: The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). Methods: Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. Results: A total of 228 patients were enrolled: 175 PM(?) without additional resection patients (group A), 21 PM(?) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months;P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). Conclusions: HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.