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Published in: Surgical Endoscopy 5/2023

Open Access 19-01-2023 | Ultrasound | Original Article

Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts

Authors: Myrte Gorris, Frederike Dijk, Arantza Farina, Johannes B. Halfwerk, Gerrit K. Hooijer, Selma J. Lekkerkerker, Rogier P. Voermans, Mattheus C. Wielenga, Marc G. Besselink, Jeanin E. van Hooft

Published in: Surgical Endoscopy | Issue 5/2023

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Abstract

Background

More accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF.

Methods

Cross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV).

Results

Overall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off ≥ 192 ng/ml) and laboratory glucose testing (cut-off ≤ 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off ≥ 20 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA ≥ 20 ng/mL versus 50% and 93% for CEA ≥ 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst).

Conclusion

Combined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (≥ 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%.

Graphical abstract

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Literature
1.
go back to reference Kromrey ML, Bulow R, Hubner J, Paperlein C, Lerch MM, Ittermann T, Volzke H, Mayerle J, Kuhn JP (2018) Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut 67:138–145CrossRefPubMed Kromrey ML, Bulow R, Hubner J, Paperlein C, Lerch MM, Ittermann T, Volzke H, Mayerle J, Kuhn JP (2018) Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut 67:138–145CrossRefPubMed
2.
go back to reference van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG (2019) Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 16:676–689CrossRefPubMed van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG (2019) Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 16:676–689CrossRefPubMed
3.
go back to reference European Study Group on Cystic Tumours of the P (2018) European evidence-based guidelines on pancreatic cystic neoplasms. Gut 67:789–804CrossRef European Study Group on Cystic Tumours of the P (2018) European evidence-based guidelines on pancreatic cystic neoplasms. Gut 67:789–804CrossRef
4.
go back to reference Tanaka M, Fernandez-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL (2017) Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 17:738–753CrossRefPubMed Tanaka M, Fernandez-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL (2017) Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 17:738–753CrossRefPubMed
5.
go back to reference Lekkerkerker SJ, Besselink MG, Busch OR, Verheij J, Engelbrecht MR, Rauws EA, Fockens P, van Hooft JE (2017) Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome. Gastrointest Endosc 85:1025–1031CrossRefPubMed Lekkerkerker SJ, Besselink MG, Busch OR, Verheij J, Engelbrecht MR, Rauws EA, Fockens P, van Hooft JE (2017) Comparing 3 guidelines on the management of surgically removed pancreatic cysts with regard to pathological outcome. Gastrointest Endosc 85:1025–1031CrossRefPubMed
6.
go back to reference Gaddam S, Ge PS, Keach JW, Mullady D, Fukami N, Edmundowicz SA, Azar RR, Shah RJ, Murad FM, Kushnir VM, Watson RR, Ghassemi KF, Sedarat A, Komanduri S, Jaiyeola DM, Brauer BC, Yen RD, Amateau SK, Hosford L, Hollander T, Donahue TR, Schulick RD, Edil BH, McCarter M, Gajdos C, Attwell A, Muthusamy VR, Early DS, Wani S (2015) Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study. Gastrointest Endosc 82:1060–1069CrossRefPubMed Gaddam S, Ge PS, Keach JW, Mullady D, Fukami N, Edmundowicz SA, Azar RR, Shah RJ, Murad FM, Kushnir VM, Watson RR, Ghassemi KF, Sedarat A, Komanduri S, Jaiyeola DM, Brauer BC, Yen RD, Amateau SK, Hosford L, Hollander T, Donahue TR, Schulick RD, Edil BH, McCarter M, Gajdos C, Attwell A, Muthusamy VR, Early DS, Wani S (2015) Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study. Gastrointest Endosc 82:1060–1069CrossRefPubMed
7.
go back to reference Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL (2004) Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126:1330–1336CrossRefPubMed Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL (2004) Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 126:1330–1336CrossRefPubMed
8.
go back to reference Jin DXSAVC, Jhala N et al (2015) A lower cyst fluid CEA cut-off increases diagnostic accuracy in identifying mucinous pancreatic cystic lesions. J Pancreas 16:271–277 Jin DXSAVC, Jhala N et al (2015) A lower cyst fluid CEA cut-off increases diagnostic accuracy in identifying mucinous pancreatic cystic lesions. J Pancreas 16:271–277
9.
go back to reference van Huijgevoort NCM, Hoogenboom SA, Lekkerkerker SJ, Topazian M, Chandrasekhara V, Morris-Stiff G, Al-Haddad MA, Oppong K, Khalid A, Del Chiaro M, Besselink MG, van Hooft JE (2018) The diagnostic accuracy of carcinoembryonic antigen in differentiating mucinous and non-mucinous pancreatic cystic neoplasms—a systematic review and individual patient data meta-analysis [abstract]. In: ESGE days 2018 accepted abstracts. Endoscopy, Budapest, Hungary, New York City, NY van Huijgevoort NCM, Hoogenboom SA, Lekkerkerker SJ, Topazian M, Chandrasekhara V, Morris-Stiff G, Al-Haddad MA, Oppong K, Khalid A, Del Chiaro M, Besselink MG, van Hooft JE (2018) The diagnostic accuracy of carcinoembryonic antigen in differentiating mucinous and non-mucinous pancreatic cystic neoplasms—a systematic review and individual patient data meta-analysis [abstract]. In: ESGE days 2018 accepted abstracts. Endoscopy, Budapest, Hungary, New York City, NY
10.
go back to reference McCarty TR, Garg R, Rustagi T (2021) Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. Gastrointest Endosc 94(698–712):e6 McCarty TR, Garg R, Rustagi T (2021) Pancreatic cyst fluid glucose in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. Gastrointest Endosc 94(698–712):e6
11.
go back to reference Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF, Group S (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351:5527CrossRef Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF, Group S (2015) STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ 351:5527CrossRef
12.
go back to reference Mohan BP, Madhu D, Khan SR, Kassab LL, Ponnada S, Chandan S, Facciorusso A, Crino SF, Barresi L, McDonough S, Adler DG (2022) Intracystic glucose levels in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. J Clin Gastroenterol 56:e131–e136CrossRefPubMed Mohan BP, Madhu D, Khan SR, Kassab LL, Ponnada S, Chandan S, Facciorusso A, Crino SF, Barresi L, McDonough S, Adler DG (2022) Intracystic glucose levels in differentiating mucinous from nonmucinous pancreatic cysts: a systematic review and meta-analysis. J Clin Gastroenterol 56:e131–e136CrossRefPubMed
13.
go back to reference Barutcuoglu B, Oruc N, Ak G, Kucukokudan S, Aydin A, Nart D, Harman M (2022) Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions. Ann Clin Biochem 59:125–133CrossRefPubMed Barutcuoglu B, Oruc N, Ak G, Kucukokudan S, Aydin A, Nart D, Harman M (2022) Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions. Ann Clin Biochem 59:125–133CrossRefPubMed
14.
go back to reference Zikos T, Pham K, Bowen R, Chen AM, Banerjee S, Friedland S, Dua MM, Norton JA, Poultsides GA, Visser BC, Park WG (2015) Cyst fluid glucose is rapidly feasible and accurate in diagnosing mucinous pancreatic cysts. Am J Gastroenterol 110:909–914CrossRefPubMed Zikos T, Pham K, Bowen R, Chen AM, Banerjee S, Friedland S, Dua MM, Norton JA, Poultsides GA, Visser BC, Park WG (2015) Cyst fluid glucose is rapidly feasible and accurate in diagnosing mucinous pancreatic cysts. Am J Gastroenterol 110:909–914CrossRefPubMed
15.
go back to reference McCarty TR, Paleti S, Rustagi T (2021) Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis. Gastrointest Endosc 93:1019–33 e5CrossRefPubMed McCarty TR, Paleti S, Rustagi T (2021) Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis. Gastrointest Endosc 93:1019–33 e5CrossRefPubMed
Metadata
Title
Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts
Authors
Myrte Gorris
Frederike Dijk
Arantza Farina
Johannes B. Halfwerk
Gerrit K. Hooijer
Selma J. Lekkerkerker
Rogier P. Voermans
Mattheus C. Wielenga
Marc G. Besselink
Jeanin E. van Hooft
Publication date
19-01-2023
Publisher
Springer US
Published in
Surgical Endoscopy / Issue 5/2023
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-022-09822-6

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