Combination of cyst fluid CEA and CA 125 is an accurate diagnostic tool for differentiating mucinous cystic neoplasms from intraductal papillary mucinous neoplasms

Background/objectivesDespite advances in imaging techniques, diagnosis and management of pancreatic cystic lesions still remains challenging. The objective of this study was to determine the utility of cyst fluid analysis (CEA, CA 19-9, CA 125, amylase, and cytology) in categorizing pancreatic cystic lesions, and in differentiating malignant from benign cystic lesions.MethodsA retrospective analysis of 68 patients with histologically and clinically confirmed cystic lesions was performed. Cyst fluid was obtained by surgical resection (n = 45) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) (n = 23). Cyst fluid tumor markers and amylase were measured and compared between the cyst types.ResultsReceiver operating characteristic (ROC) curve analysis of the tumor markers demonstrated that cyst fluid CEA provided the greatest area under ROC curve (AUC) (0.884) for differentiating mucinous versus non-mucinous cystic lesions. When a CEA cutoff value was set at 67.3 ng/ml, the sensitivity, specificity and accuracy for diagnosing mucinous cysts were 89.2%, 77.8%, and 84.4%, respectively. The combination of cyst fluid CEA content >67.3 ng/ml and cyst fluid CA 125 content >10.0 U/ml segregated 77.8% (14/18) of mucinous cystic neoplasms (MCNs) from other cyst subtypes. On the other hand, no fluid marker was useful for differentiating malignant versus benign cystic lesions. Although cytology (accuracy 83.3%) more accurately diagnosed malignant cysts than CEA (accuracy 65.6%), it lacked sensitivity (35.3%).ConclusionsOur results demonstrate that cyst fluid CEA can be a helpful marker in differentiating mucinous from non-mucinous, but not malignant from benign cystic lesions. A combined CEA and CA 125 approach may help segregate MCNs from IPMNs.     

Cyst fluid SPINK1 may help to differentiate benign and potentially malignant cystic pancreatic lesions

ObjectiveDifferential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions.DesignSixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at ?70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type).ResultsThe acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13–3602) vs. 18 (0.1–278) μg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2–116] μg/L) than in main duct IPMN or MCA (638 [66–3602] μg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 μg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 μg/L).ConclusionsCyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions.     

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis

BACKGROUND: Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the value of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. METHODS: A search in PubMed was performed with the search terms cyst, pancrea, and fluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scatter grams. Cutoff levels were determined. RESULTS: Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% of MCAC (n = 111). DISCUSSION: Most pancreatic cystic tumors should be resected without the need for cyst fluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine the optimal therapeutic strategy.     

Role of cystic fluid in diagnosis of the pancreatic cystadenoma and cystadenocarcinoma

BACKGROUND/AIMS: Early and accurate diagnosis of cystic neoplasm of the pancreas is difficult especially for the differentiation of benign or malignancy. In this study, we try to compare EUS-guided fine needle aspiration biopsy combined with measurement of the cyst fluid and serum levels of CEA, and CA19-9 for the preoperative diagnosis of pancreatic cystadenoma or cystadenocarcinoma. METHODOLOGY: Retrospective analysis was made on the clinical data of 37 patients with pancreatic cystadenoma and 48 patients with cystadenocarcinoma from 1998 to 2005. RESULTS: Carcinoembryonic antigen (CEA), and CA19-9 of the cyst fluid and serum combined with EUS-guided fine needle aspiration biopsy was made. Examination of serum CEA, and CA19-9 resulted in 21.0+/-18.0, 2.7+/-1.7 U/L and 18.7+/-17.5, 269.0+/-182.0 U/L for cystadenoma and cystadenocarcinoma respectively (P<0.05). The sensitivity of cyst fluid combined with biopsy was higher than that of a single marker. However, the sensitivity and specificity of tumor markers of cystic fluid were much higher than that of the serum (P<0.05). CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid level of CEA and CA19-9 will be a credible means for early diagnosis of pancreatic cystadenoma and cystadenocarcinoma.     

Cytopathological Analysis of Cyst Fluid Enhances Diagnostic Accuracy of Mucinous Pancreatic Cystic Neoplasms

Widespread use of cross-sectional imaging and increasing age of the general population has increased the number of detected pancreatic cystic lesions. However, several pathological entities with a variety in malignant potential have to be discriminated to allow clinical decision making. Discrimination between mucinous pancreatic cystic neoplasms (PCNs) and nonmucinous pancreatic lesions is the primary step in the clinical work-up, as malignant transformation is mostly associated with mucinous PCN. We performed a retrospective analysis of all resected PCN in our tertiary center from 2000 to 2014, to evaluate preoperative diagnostic performance and the results of implementation of the consensus guidelines over time. This was followed by a prospective cohort study of patients with an undefined pancreatic cyst, where the added value of cytopathological mucin evaluation to carcinoembryonic antigen (CEA) in cyst fluid for the discrimination of mucinous PCN and nonmucinous cysts was investigated. Retrospective analysis showed 115 patients operated for a PCN, with a correct preoperative classification in 96.2% of the patients. High-grade dysplasia or invasive carcinoma was observed in only 32.3% of mucinous PCN. In our prospective cohort (n = 71), 57.7% of patients were classified as having a mucinous PCN. CEA ≥192 ng/mL had an accuracy of 63.4%, and cytopathological mucin evaluation an accuracy of 73.0%. Combining these 2 tests further improved diagnostic accuracy of a mucinous PCN to 76.8%. CEA level and mucin evaluation were not predictive of the degree of dysplasia. These findings show that adding cytopathology to cyst fluid biochemistry improves discrimination between mucinous PCN and nonmucinous cysts.     

内镜超声引导下细针穿刺细胞学及囊液癌胚抗原分析诊断胰腺囊性病变的价值

目的探讨内镜超声引导下细针穿刺（EUS-FNA）细胞学检查、囊液癌胚抗原（cEA）分析对区分胰腺囊性病变良恶性的诊断价值。方法对27例胰腺囊性病变患者行EUS-FNA细胞学检查和囊液CEA分析,绘制囊液CEA受试者工作特征曲线并通过Youden指数确定诊断临界值,以手术病理诊断为金标准,统计分析EUS、EUS-FNA细胞学及囊液CEA分析鉴别诊断胰腺囊性病变良恶性的敏感度、特异度、阳性预测值、阴性预测值和准确率。结果手术病理确诊良性病变14例、潜在恶性／恶性病变13例。EUS鉴别诊断胰腺囊性病变良恶性的准确率、敏感度、特异度、阳性预测值、阴性预测值分别为77．8％（21／27）、69．2％（9／13）、85．7％（12／14）、81．8％（9／11）、75．0％（12／16）;EUS-FNA细胞学上述指标分别为85．2％（23／27）、76．9％（10／13）、92．9％（13／14）、90．9％（10／11）、81．3％（13／16）;以囊液CEA值22．24ng／ml为诊断临界值,上述指标分别为74．1％（20／27）、84．6％（11／13）、64．3％（9／14）、68．8％（11／16）、81．8％（9／11）。结论EUS-FNA细胞学鉴别诊断胰腺囊性病变良恶性具有较高的准确率和特异度,而囊液CEA分析（诊断临界值22．24ng／m1）鉴别诊断胰腺囊性病变良恶性的敏感度较高,选择合适的胰腺囊液CEA分析诊断临界值结合EUS-FNA细胞学检查可以基本满足临床鉴别胰腺囊性病变良恶性的需要。     

Cyst fluid analysis obtained by EUS-guided FNA in the evaluation of discrete cystic neoplasms of the pancreas: a prospective single-center experience

BACKGROUND: Accurate assessment of pancreatic cystic neoplasms is imperative before selecting available treatment options, such as surgical resection, drainage, or conservative therapy. Available modalities, CT and magnetic resonance imaging, have been inconsistent in diagnosis. Reports involving EUS and cyst fluid analysis have been encouraging, including studies of EUS features and/or cyst fluid analysis, which may differentiate pancreatic cystic neoplasms. OBJECTIVE: To retrospectively determine cyst fluid characteristics that differentiate cystic neoplasms. DESIGN: Patient evaluation included (1) EUS features (reported elsewhere) and (2) cyst fluid analysis (carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA 19-9], amylase and lipase, viscosity [VIS], mucin stain, and cytology). Exclusion criteria included the following: intraductal papillary mucinous tumor lesions, bloody cyst aspirate, neuroendocrine tumors, and patients without surgical histopathology. SETTING: Pancreatic Biliary Center, St Luke's Medical Center, Milwaukee, Wisconsin. PATIENTS: A total of 102 patients (60 women, 42 men; age, 23-76 years) presented for evaluation of pancreatic cystic neoplasm; 71 underwent surgical resection. RESULTS: Seventy-one of 102 patients who underwent surgery presented the following histopathologic correlates: 23 pseudocysts (PC), 13 serous cystadenoma (SCyA), 21 mucinous cystadenoma (MCyA), and 14 mucinous cystadenocarcinoma (MCyA-CA). Cyst fluid analysis of these patients showed the following: VIS was lower in PC (mean, 1.3) and SCyA (1.27) when compared with MCyA (1.84) and MCyA-CA (1.9). All mucinous neoplasms had VIS >1.6, whereas only 2 mucinous cystic neoplasms (MCN) had VIS = 1.6 (both PC). The CEA level was significantly higher in MCyA (adenoma [878 ng/mL], carcinoma [27,581 ng/mL]) vs PC (189 ng/mL), and SCyA (121 ng/mL). Amylase levels were higher in PC (7210 U/L) compared with cystic neoplasm (SCyA, 679 U/L; MCyA, 1605 U/L; MCyA-CA, 569 U/L). CONCLUSIONS: Differential diagnosis of pancreatic cystic neoplasm is significantly enhanced by cyst fluid analysis. Elevated CEA (> or =480 ng/mL) and VIS (>1.6) accurately predict MCN from SCyA and PC. Malignant from benign MCN can be differentiated by CEA levels > or =6000 ng/mL.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Mucinous biliary cystadenoma with mesenchymal stroma: Expressions of CA 19-9 and carcinoembryonic antigen in serum and cystic fluid

a case of mucinous biliary cystadenoma with mesenchymal stroma (CMS tumor) in a 64-year-old woman is reported. The patient presented with acute abdominal pain and a palpable mass in the upper abdomen. Computed tomography and abdominal sonography showed characteristic multilocular cysts in the left lobe of the liver. Serum CA 19-9 was elevated to 108 U/ml with normal carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels. The levels of CA 19-9 and CEA in the cystic fluid were high at 7430 U/ml and 576ng/ml, respectively. The serum CA 19-9 returned to 35 U/ml 4 weeks after tumor resection. These corresponding findings of both tumor markers in the serum and cystic fluid imply that (1) CA 19-9 and CEA both exist in the epithelial component of CMS tumors as evidenced by immunohistochemical stain, (2) serum CA 19-9 is a valuable marker in the diagnosis and monitoring of CMS, and (3) in cystic fluid, there are more significantly high levels of CA 19-9 in CMS compared with levels in simple cyst and polycystic liver disease. Therefore, measurement of CA 19-9 in cystic fluid and serum may be helpful in the differential diagnosis of hepatic cystic lesions.     

A comparative analysis of K-ras mutation and carcinoembryonic antigen in pancreatic cyst fluid

Background/aimsAnalysis of cystic fluid may be useful in distinguishing between benign and malignant cysts which has significant impact on their management. The aim of our study was to assess the diagnostic utility of carcinoembryonic antigen (CEA) and K-ras gene mutation in pancreatic cysts fluid.MethodsThe study included 56 patients with pancreatic cystic fluid collected for analysis. The cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) - 39 patients or premalignant/malignant (mucinous cystadenoma, IPMN, cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations and presence of K-ras mutation were analyzed.ResultsCEA were higher in patients with malignant cysts (mean levels 238 ± 12.5 ng/ml; range 32.8–4985 ng/ml) compared to benign lesions (mean levels 34.5 ± 3.7 ng/ml; range 3.9–693 ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with premalignant/malignant lesions. It was also detected in 1 patient with final diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p < 0.01). If CEA and molecular analysis were combined in that cysts with either CEA level>45 ng/ml or presence of K-ras mutation, than 16 of 17 premalignant/malignant cysts were correctly identified (94.1%).ConclusionMolecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis and should be considered when cyst cytologic examination is negative for malignancy.     

Improved early diagnosis of cystadenocarcinoma of the pancreas

IntroductionT here are great differences between the therapy for cystadenocarcinomas and benign pancreatic lesions. Early diagnosis is propitious to selecting the appropriate therapy, and may directly influence the prognosis.[1-4] Differential diagnosis between cystadenocarcinoma and benign pancreatic lesion is difficult, because they lack typical clinical symptoms in early stage. In the commonly used examinations, the specificity of B-ultrasonography (B-US) and CT is very poor; they are di…     

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/premalignant 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 cutoffs were 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.     

Cystic Lesions of the Pancreas: A Diagnostic and Management Dilemma

Background/Aims: Due to enhanced imaging modalities, pancreatic cysts are being increasingly detected, often as an incidental finding. They comprise a wide range of differing underlying pathologies from completely benign through premalignant to frankly malignant. The exact diagnostic and management pathway of these cysts remains problematic and this review attempts to provide an overview of the pathology underlying pancreatic cystic lesions and suggests appropriate methods of management. Methods: A search was undertaken with a Pubmed database to identify all English articles using the keywords ‘pancreatic cysts’, ‘serous cystadenoma’, ‘intraductal papillary mucinous tumour’, ‘pseudocysts’, ‘mucinous cystic neoplasm’ and ‘solid pseudopapillary tumour’. Results: The mainstay of assessment of pancreatic cysts is cross-sectional imaging incorporating CT and MRI. Fine-needle aspiration (FNA) (often with endoscopic ultrasound) may provide valuable additional information but can lack sensitivity. Symptomatic cysts, increasing age and multilocular cysts (with a solid component and thick walls) are predictors of malignancy. A raised cyst aspirate CEA, CA 19-9 and mucin content (including abnormal cytology), if present, can accurately distinguish premalignant and malignant cysts from benign ones. Conclusion: In summary, all patients with pancreatic cystic lesions, whether asymptomatic or symptomatic, must be thoroughly investigated to ascertain the underlying nature of the cyst. Small asymptomatic cysts (<3 cm) with no suspicious features on imaging or FNA may be safely followed up. Follow-up should continue for at least 4 years, with a repeat FNA if needed. An algorithm for the management of pancreatic cystic tumours is also suggested.     

Epidermoid cyst of the intrapancreatic accessory spleen producing CA19‐9

We report a rare case of an epidermoid cyst in an accessory spleen at the pancreatic tail with producing CA19‐9. A 55‐year‐old female was admitted to our hospital, Cancer Research Institute, Kanazawa University, for close examination of a cystic lesion at the pancreatic tail and a high serum CA19‐9‐value (176 U/mL). There were almost no abdominal symptoms related to the cystic lesion. A cystic tumor approximately 3 cm in diameter and composed of multilocular cysts without a protruding portion of the inner surface was found at the pancreatic tail by ultrasound sonography, computed tomography, and magnetic resonance imaging. Endoscopic retrograde pancreatography revealed that the main pancreatic duct shifted at the pancreatic tail and there was no communication between the main pancreatic duct and cystic lesion. Based on a preoperative diagnosis of mucinous cystic tumor, distal pancreatectomy with splenectomy was performed. Histological ?ndings suggested an epidermoid cyst (3.5 × 3.0 cm) originating from an intrapancreatic accessory spleen. Immunohistochemical analysis of CA19‐9 in the epidermoid cyst showed clear staining of the inner epithelium of the cyst and amorphous or hyalinous cystic contents. The serum CA19‐9 value was con?rmed to decline to normal 2 months after resection. Physicians should not forget this disease during differential diagnosis related to pancreatic cystic lesions with elevated levels of serum tumor markers, such as CA19‐9 or carcinoembryonic antigen, although this disease is extremely rare.     

Imaging of indeterminate pancreatic cystic lesions: A systematic review

BackgroundPancreatic cystic lesions are an increasing problem and investigation of these cysts can be fraught with difficulty. There is currently no gold standard for diagnosis or surveillance. This review was undertaken to determine the present reliability of the characterisation, assessment of malignant potential and diagnosis of pancreatic cystic lesions using available imaging modalities.MethodsA Medline search using the terms ‘pancreatic’, ‘pancreas’, ‘cyst’, ‘cystic’, ‘lesions’, ‘imaging’, ‘PET’. ‘CT’, ‘MRI’ and ‘EUS’ was performed. Publications were screened to include studies examining the performance of CT, MRI, MRCP, EUS and 18-FDG PET in the determination of benign or malignant cysts, cyst morphology and specific diagnoses.ResultsNineteen studies were identified that met the inclusion criteria. 18-FDG PET had a sensitivity and specificity of 57.0–94.0% and 65.0–97.0% and an accuracy of 94% in determining benign versus malignant cysts. CT had a sensitivity and specificity of 36.3–71.4% and 63.9–100% in determining benign disease but had an accuracy of making a specific diagnosis of 39.0–44.7%. MRI had a sensitivity and specificity of 91.4–100.0% and 89.7% in assessing main pancreatic duct communication.ConclusionCT is a good quality initial investigation to be used in conjunction with clinical data. MRCP can add useful information regarding MPD communication but should be used judiciously. PET may have a role in equivocal cases to determine malignancy. Further examination of CT-PET in this patient group is warranted.     

Novel serum tumor marker, RCASl, in pancreatic diseases

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma.     

Novel serum tumor marker, RCAS1, in pancreatic diseases

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma.     

The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma

BACKGROUND/AIMS: CA 19-9 and CEA were evaluated for their specificity and sensitivity in the early diagnosis of pancreatic carcinoma. METHODOLOGY: This prospective study included 40 patients with pancreatic carcinoma. A control group of 60 patients were divided into two subgroups as upper gastrointestinal system malignancies and benign pancreatic disorders. CEA and CA 19-9 levels were measured in all the patients. RESULTS: When the reference value of CA 19-9 was accepted as 74 U/mL, the specificity was 100% when pancreatic carcinoma was compared with benign disorders of the pancreas, but it's specificity for upper gastrointestinal malignancies was 60-90%. When the reference value of CEA was increased, the sensitivity had been decreased but the specificity had been increased when compared with the control group. If the reference value of CEA was accepted as 5 ng/mL, the specificity was 100% when pancreatic carcinoma was compared with acute or chronic pancreatitis, but it is less specific for the differential diagnosis of pancreatic carcinoma from the upper gastrointestinal malignancies. CONCLUSIONS: With the progression of the pancreatic carcinoma, serum CEA level and the specificity of CEA were elevated similar to that of CA 19-9. However, the elevation of CEA specificity when compared with the control group was lower than the specificity of the CA 19-9 and the sensitivity of CA 19-9 was superior to that of CEA for pancreatic carcinoma. The level of CA 19-9 was increased with the development of early pancreatic cancer and this elevation steadily continued with the progression of the cancer.     

肿瘤标志物、K-ras和p53突变对胰腺癌诊断的价值

目的评价血清肿瘤标志物CA19-9、CA242、CA50、癌胚抗原和粪便K-ras以及p53基因突变对胰腺癌诊断的价值。方法收集2002年2月至2004年3月在北京协和医院、中国医学科学院肿瘤医院和沈阳军区总医院确诊的新发胰腺癌患者136例,良性消化系统疾病患者240例,进行血清肿瘤标志物和粪便K-ras、p53基因突变的检测。根据结果绘制不同检测方法的受试者工作特征(ROC)曲线,计算ROC曲线下面积,并确定最佳阳性分界值。结果血清CA19-9和CA242的ROC曲线下面积分别为0·855±0·031(95%可信区间0·794~0·916)和0·859±0·031(95%可信区间0·799~0·920),最佳阳性分界值分别为68U/ml和25U/ml,其诊断胰腺癌的敏感性分别为84·4%(98/116)和88·4%(84/95),特异性分别为84·3%(145/172)和79·1%(144/182)。粪便K-ras和p53基因突变诊断胰腺癌的敏感性分别为77·8%和27·8%,特异性分别为82·2%和95·2%。将粪便K-ras和p53基因突变与血清CA19-9和CA242测定相结合计算胰腺癌诊断评分,绘制有序分类资料的ROC曲线,其曲线下面积为0·946±0·017(95%可信区间0·912~0·980),最佳阳性分界值为2分。结论血清CA19-9及CA242对胰腺癌诊断具有相似价值;联合粪便K-ras及p53突变的检测,通过胰腺癌可能性积分,可以显著提高胰腺癌的诊断效率。     

Optimize CA19-9 in detecting pancreatic cancer by Lewis and Secretor genotyping

BackgroundCarbohydrate antigen 19-9 (CA19-9) is currently the most widely used biomarker for pancreatic cancer. It is well-known that Lewis and Secretor status can affect CA19-9 biosynthesis. This study was performed to optimize CA19-9 in detecting pancreatic cancer using Lewis and Secretor dependent cut-off values.MethodsLewis and Secretor genotypes were determined by Sanger sequencing in a large cohort of subjects (578 cases with pancreatic cancer, 210 cases with benign pancreatic disease, 315 normal subjects). The effectiveness of CA19-9 for detecting pancreatic cancer using Lewis and Secretor group dependent cut-off values was evaluated.ResultsThe Lewis (-), Mixed, and Secretor (-) groups had low, medium, and high CA19-9 biosynthesis, respectively. In Lewis (-) pancreatic cancer (all stages), CA19-9 had a sensitivity of 48.6% and a specificity of 95.9% when 1.8 U/mL was used as the cut-off value. The sensitivity of CA19-9 in detecting all stages of pancreatic cancer improved from 80.1% to 88.0% and the negative predictive value increased from 81.2% to 87.1% without compromising other values when using group dependent cut-off values. The sensitivity of CA19-9 for the detection of stage I, II pancreatic cancer increased from 76.1% to 87.2%.ConclusionsThe value of CA19-9 in detecting pancreatic cancer was optimized by using group dependent cut-off values based on Lewis and Secretor genotypes. CA19-9 can be applied as an early detector of pancreatic cancer using group dependent cut-off values.