Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study

Gaddam, Srinivas; Ge, Phillip S.; Keach, Joseph Walker; Mullady, Daniel; Fukami, Norio; Edmundowicz, Steven A.; Azar, Riad R.; Murad, Faris; Kushnir, Vladimir; Watson, Rabindra R.; Ghassemi, Kourosh F.; Sedarat, Alireza; Komanduri, Srinadh; Jaiyeola, Diana; Brauer, Brian C.; Yen, Roy D.; Amateau, Stuart K.; Hosford, Lindsay; Hollander, Thomas; Donahue, Timothy R.; Schulick, Richard D.; Edil, Barish H.; McCarter, Martin D.; Gajdos, Csaba; Attwell, Augustin; Muthusamy, V. Raman; Early, Dayna S.; Wani, Sachin

doi:10.1016/j.gie.2015.04.040

Cited by 81 publications

(73 citation statements)

References 49 publications

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“…The level of CEA in the cyst fluid may help distinguish mucinous from non-mucinous cysts [11], but this test leaves much ambiguity. A recent study found a sensitivity of 61% and specificity of 77%, resulting in a misclassification of 39% of mucinous cases [12], which is similar to previous findings [11, 13, 14]. The lack of clarity has produced much debate about optimal indications for surgical resection [15], with the goal of balancing the potentially positive outcome from removing a dangerous lesion against the negative consequences of an unnecessary procedure.…”

Section: Introductionsupporting

confidence: 69%

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

et al. 2016

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Molecular indicators to specify the risk posed by a pancreatic cyst would benefit patients. Previously we showed that most cancer-precursor cysts, termed mucinous cysts, produce abnormal glycoforms of the proteins MUC5AC and endorepellin. Here we sought to validate the glycoforms as a biomarker of mucinous cysts and to specify the oligosaccharide linkages that characterize MUC5AC. We hypothesized that mucinous cysts secrete MUC5AC displaying terminal N-acetylglucosamine (GlcNAc) in either alpha or beta linkage. We used antibody-lectin sandwich assays to detect glycoforms of MUC5AC and endorepellin in cyst fluid samples from three independent cohorts of 49, 32, and 66 patients, and we used monoclonal antibodies to test for terminal, alpha-linked GlcNAc and the enzyme that produces it. A biomarker panel comprising the previously-identified glycoforms of MUC5AC and endorepellin gave 96%, 96%, and 87% accuracy for identifying mucinous cysts in the three cohorts with an average sensitivity of 92% and an average specificity of 94%. Glycan analysis showed that MUC5AC produced by a subset of mucinous cysts displays terminal alpha-GlcNAc, a motif expressed in stomach glands. The alpha-linked glycoform of MUC5AC was unique to intraductal papillary mucinous neoplasms (IPMN), whereas terminal beta-linked GlcNAc was increased in both IPMNs and mucinous cystic neoplasms (MCN). The enzyme that synthesizes alpha-GlcNAc, A4GNT, was expressed in the epithelia of mucinous cysts that expressed alpha-GlcNAc, especially in regions with high-grade dysplasia. Thus IPMNs secrete a gastric glycoform of MUC5AC that displays terminal alpha-GlcNAc, and the combined alpha-GlcNAc and beta-GlcNAc glycoforms form an accurate biomarker of mucinous cysts.

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Section: Introductionsupporting

confidence: 69%

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

et al. 2016

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“…13 Cyst fluid CEA has been widely used for the differentiation of mucinous and nonmucinous cysts, but recent reports cast doubt on its usefulness. 14,15 Although mucinous cysts are potentially malignant, surgical resection is not always the first choice because of its invasiveness. It was estimated that in elderly patients with comorbidities, noninvasive surveillance, or even doing nothing, can be the management of choice in terms of quality-adjusted life-years.…”

Section: Discussionmentioning

confidence: 99%

Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements

Nakai

Iwashita

Shinoura

et al. 2016

Gastrointestinal Endoscopy

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Background and Aims Pancreatic cystic neoplasms (PCNs) often need interval surveillance, including repeat EUS, but the role of repeat FNA with fluid analysis is poorly defined. The aim of this analysis is to evaluate the potential clinical significance of serial carcinoembryonic antigen (CEA) measurements by EUS-guided FNA (EUS-FNA) in the surveillance for PCNs. Patients Patients who underwent EUS-FNA for PCNs were studied retrospectively. EUS-FNA findings were compared between index and prior procedures among patients who underwent repeat EUS-FNA. Results A total of 400 patients with PCNs underwent EUS-FNA. Eighty-seven of those patients had prior EUS-FNA with cyst fluid analysis. Patients with repeat FNA were significantly more likely to have multiple cysts (57% vs 41%; P = .008), multilocular cysts (75% vs 62%; P = .042), connection to pancreatic duct (33% vs 18%; P = .005), and higher initial CEA levels (94.8 vs 25.6 ng/mL; P = .003) compared with patients who had only a single FNA. A comparison of prior and index FNAs did not show significant differences in EUS or cyst fluid analysis findings. After log transformation, the association between CEA level at prior and index FNA was moderate (R2 = 0.626; P < .001), but cystic fluid CEA classification with a cutoff value of 192 ng/mL changed in 17 patients (20%), without significant changes in EUS findings. Conclusions Repeat surveillance EUS-FNA resulted in stable CEA levels in the majority of patients, with spurious fluctuations of CEA in approximately 20% of patients. These data call into question any clinical significance attributed to an isolated interval rise in CEA level, especially in light of a stable EUS examination.

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“…Perhaps the most widely used pancreatic cyst fluid biomarker is CEA(16). CEA is able to differentiate mucinous from non-mucinous type cysts with an accuracy of 77% according to a large multi-institutional validation study of 1,861 patients(17). However, CEA alone lacks sufficient accuracy for routine identification of mucinous cysts and does not correlate with grade of dysplasia(18–20).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasia

Yip-Schneider

Carr

et al. 2017

Journal of the American College of Surgeons

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Background With the increased frequency of diagnostic imaging, pancreatic cysts are now detected in >3% of American adults. Most of these are intraductal papillary mucinous neoplasm (IPMN) with well-established but variable malignant potential. A biomarker that predicts malignant potential or dysplastic grade would help determine which IPMN require removal or can be safely observed. We previously reported that pancreatic fluid prostaglandin E2 (PGE2) levels may have promise as a predictor of IPMN dysplasia and seek to validate these results in the current study. Study Design Pancreatic cyst/duct fluid was prospectively collected from 100 patients with IPMN undergoing pancreatic resection. Surgical pathology revealed 47 low/moderate grade, 34 high grade, and 20 invasive IPMN. PGE2 levels were assessed by enzyme-linked immunoassay and correlated with IPMN dysplasia grade, demographics, clinical radiologic/pathologic variables, acute/chronic pancreatitis and non-steroidal anti-inflammatory drug use. Results Mean pancreatic cyst fluid PGE2 levels in high grade and invasive IPMN were significantly higher than low/moderate grade IPMN (3.5 and 4.4 respectively versus 1.2pg/µl, p<0.0016). At a threshold of 1.1pg/µl, PGE2 was 63% sensitive, 79% specific, and 71% accurate for detection of high grade/invasive IPMN. When tested in the subset of IPMN patients with preoperative pancreatic cyst fluid CEA >192ng/mL, PGE2 at a threshold of 0.5pg/µl demonstrated 78% sensitivity and 100% specificity, and 86% accuracy for detection of high grade/invasive IPMN. Conclusions Our results validate pancreatic cyst fluid PGE2 as an indicator of IPMN dysplasia especially in select patients with preoperative pancreatic cyst fluid CEA >192ng/mL. The inclusion of PGE2/CEA in a diagnostic biomarker panel may facilitate more optimal treatment stratification of IPMN patients.

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Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study

Cited by 81 publications

References 49 publications

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

A Gastric Glycoform of MUC5AC Is a Biomarker of Mucinous Cysts of the Pancreas

Role of serial EUS-guided FNA on pancreatic cystic neoplasms: a retrospective analysis of repeat carcinoembryonic antigen measurements

Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasia

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