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Background and Objectives: Pancreatic cysts have various potential for malignant transformation. Differentiating mucinous from non-mucinous cysts is crucial to make the right decision about further management, since mucinous cysts carry the risk of malignancy. Using endoscopic ultrasound (EUS) guided fine needle aspiration to determine intracystic carcinoembryonic antigen (CEA) levels is the recommended method for identifying mucinous cysts, although intracystic glucose assessment has also proved to be an effective tool. This study aims to compare the diagnostic performance of intracystic glucose and CEA in distinguishing between mucinous and non-mucinous pancreatic cystic lesions., Methods: In this single center study, we prospectively collected and analyzed the data of 91 consecutive patients who underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with cytological analysis and measurement of intracystic CEA and glucose levels. The cyst type was classified based on radiological and EUS morphology, string sign, CEA, cytological and histological findings in resected cases. The diagnosis was established retrospectively by three experienced gastroenterologists blinded for glucose level in cases without definitive cytology or histology. We calculated the sensitivity, specificity, the positive- and negative predictive value of glucose and CEA respectively, and compared the two methods., Results: The sensitivity of intracystic glucose versus CEA proved to be 96.2% vs. 69.2% in identifying mucinous cysts, while the specificity of glucose was shown to be 79.5%, compared to 100% for CEA., Conclusion: Intracystic glucose is a sensitive, easily accessible biomarker in identifying mucinous pancreatic cysts, however, the specificity is lower compared to CEA. The measurement of intracystic glucose level could help in decision-making in daily clinical practice, however the diagnostic performance of the method remains inferior to "through-the-needle" techniques, such as confocal laser endomicroscopy and Moray forceps biopsy., Competing Interests: IH received consultation fee from Olympus GmbH. Author GG was employed by Spital Thurgau AG Münsterlingen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gyimesi, Keczer, Rein, Horváth, Szűcs, Marjai, Szijártó and Hritz.)

Background: Distinguishing mucinous (M) pancreatic cystic neoplasms (PCNs) from non-mucinous (NM) is challenging but crucial. Low intracystic glucose level has shown diagnostic tool promise, however further investigation is needed to understand metabolic processes., Aims: To compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker., Methods: PCNs≥15 mm which underwent EUS-fine needle aspiration were prospectively enrolled. Glucose, CEA and lactate levels were measured. Diagnostic accuracy for M-PCN diagnosis was evaluated using surgical/cytology reports or multidisciplinary evaluations., Results: 169 PCNs were included (64 % M-PCNs). Median intracystic glucose was significantly lower in M-PCNs (1 mg/dL) compared to NM-PCNs (101 mg/dL); mean intracystic CEA was significantly higher in M-PCNs (152.5 ng/mL) compared to NM-PCNs (0.3 ng/mL). ROC curve analysis revealed best glucose cut-off ≤58 mg/dL (accuracy 93.5 %) and CEA cut-off >2.5 ng/mL (accuracy 90.5 %) for M-PCNs. Intracystic lactates were significantly lower in M-PCNs correlating directly with glucose. Single glucose dosage evidenced best diagnostic accuracy respect markers combination., Conclusion: Intracystic glucose demonstrated high diagnostic utility for M-PCNs differentiation, surpassing CEA. Lactate levels correlated with glucose, suggesting their uptake by M-PCNs cells. These findings contribute to a better metabolic landscape understanding glucose use as diagnostic marker., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The accuracy and costs of current diagnostic methods in the differential diagnosis of pancreatic cystic lesions still has ample room for improvement., Aims: The aim of the study was to confirm the diagnostic yield of intracystic glucose in the diagnosis of pancreatic cyst subtypes., Methods: We prospectively recruited all patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration of pancreatic cyst at our Institution., Results: Fifty-six patients were included in the study. We found that intracystic glucose concentration < 50 mg/dL was significantly more sensitive than a concentration of Carcinoembryonic Antigen > 192 ng/mL (93.6% vs 54.8%; p = 0.003) for the diagnosis of mucinous cysts. In terms of specificity, the two markers were not different (96% vs 100%; p = 1). Regarding the diagnosis of non-mucinous cysts, intracystic glucose concentration ≥ 50 mg/mL showed higher sensitivity than Carcinoembryonic Antigen level < 5 ng/mL (96% vs 72%) although a statistical significance could not be reached (p = 0.07). The two markers were not statistically different in terms of specificity (93.6% vs 87.1%; p = 0.62)., Conclusion: Given its diagnostic performance and ease of measurement, intracystic glucose may replace Carcinoembryonic Antigen in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts., Competing Interests: Declaration of Competing Interest Claudio De Angelis is consultant for Boston Scientific., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described., Aims: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis., Materials and Methods: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological., Results: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis., Conclusion: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

Background: The most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen., Methods: Pancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed., Results: Cyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92., Conclusion: Cyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts., (Copyright © 2017. Published by Elsevier Inc.)

Background and Aim: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN)., Methods: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated., Results: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05)., Conclusion: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved., (© 2016 Japan Gastroenterological Endoscopy Society.)

Background: Management of pancreatic cysts is based on neoplastic-nonneoplastic discrimination. Endoscopic ultrasound (EUS) enables to differentiate neoplastic-nonneoplastic lesions and also allows fine-needle aspiration (FNA). In this study, we aim to assess feasibility and clinical relevance of cytological and biochemical analysis in differential diagnosis of cystic pancreatic lesions in patients who had undergone endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) due to pancreatic cysts., Methods: Participants were 96 patients who had undergone EUS-FNA for differential diagnosis of pancreatic cysts. Pancreatic cysts were classified as benign-mucinous, nonmucinous, and malignant according to patient history, physical examination, EUS appearance, and cystic fluid assessment. Tumor markers (CEA, CA(cancer antigens) 72.4, CA 19-9) , amylase, lipase and cytological assesment were compared between 3 different groups. Receiver-operating characteristics (ROC) curves were constructed to identify appropriate cut-off values., Results: Fluid CEA and CA 72.4 levels for benign-mucinous and malignant cysts were significantly higher than for nonmucinous cysts (P ≤ 0.04). A cut-off CEA level of 207 ng/mL differentiated mucinous etiology with a sensitivity of 72.7%, specificity of 97.7%, and accuracy of 89.5%. The sensitivity, specificity, and accuracy of the CA 72.4 cut-off level of 3.32 ng/mL were 80%, 69.5%, and 73.6%, respectively., Conclusion: Cyst fluid CEA and CA 72.4 levels have a high accuracy in discriminating mucinous from nonmucinous cysts. When combined with cytology their accuracy rate increases., Competing Interests: The authors have no funding and conflicts of interests to disclose.

Objectives: Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip., Methods: Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed., Results: Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00)., Conclusions: Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

Objective: Cyst fluid amylase is a potential marker for pseudocysts and intraductal papillary mucinous neoplasms (IPMN). This study aimed to evaluate the diagnostic role of cyst fluid amylase and to determine the optimal cutoff values of cyst fluid amylase and carcinoembryonic antigen (CEA) for the differential diagnosis of pancreatic cysts., Methods: Based on the pancreatic cyst database at Massachusetts General Hospital, a total of 78 patients with histologically proven cysts [pancreatic pseudocyst (PP), n = 16; mucinous cystic neoplasm, mucinous cystic neoplasm (MCN), n = 22; IPMN, n = 40] were selected. Complete cyst fluid amylase and CEA values were analyzed., Results: Thirty two of 78 patients were male with median age of 60.4 years (range, 24-84). Cyst diameter ranged from 5 to 130 mm. For cyst fluid amylase, there was significant difference between PP and MCN (median, 30,034.50 vs. 4,723.50 U/L; p < 0.05) or IPMN (30,034.50 vs. 1,585.00; p = 0.001), but no difference between MCN and IPMN. For cyst fluid CEA, there was a significant difference between PP and MCN (median, 26.00 vs. 627.50 ng/mL; p < 0.001) or IPMN (26.00 vs. 356.50; p < 0.001). Median amylase and CEA values were significantly different between PP and mucinous neoplasms (MCN/IPMN) (p < 0.01 and p < 0.001). Optimal cutoff values of 6,800 U/mL for amylase and 50 ng/mL for CEA correlated with the crossover of the sensitivity and specificity curves for differentiating PP and mucinous neoplasms. The overall accuracies of cyst fluid amylase and CEA were 69 and 85%, respectively., Conclusions: Cyst fluid amylase analysis does not differentiate between MCN and IPMN. The combination of cyst fluid CEA and amylase value may increase the diagnostic accuracy for differentiating mucinous neoplasms from pseudocysts.

Background: Using carcinoembryonic antigen in discriminating between benign and malignant disease remains controversial., Aims: We aim to evaluate the diagnostic accuracy of cyst fluid carcinoembryonic antigen in predicting malignant pancreatic cystic lesions., Methods: We performed a literature search of MEDLINE and EMBASE. We included studies that compared the diagnostic accuracy of carcinoembryonic antigen with histology. Pooled estimates of diagnostic precision were calculated using random-effects models., Results: Eight studies (504 patients) were included. The carcinoembryonic antigen cutoff level for determining a malignant cyst ranged from 109.9 to 6000 ng/mL. Pooled estimates of carcinoembryonic antigen in malignant cysts prediction were poor: pooled sensitivity of 63%, pooled specificity of 63%. The positive likelihood ratio was 1.89 and the negative likelihood ratio was 0.62. The diagnostic odds ratio was 3.84. The area under the summary receiver-operating characteristic curve was 0.70. In subgroup analysis of patients with mucinous cysts (mucinous cystic neoplasm and intraductal papillary mucinous neoplasm; 5 studies, 227 patients), pooled sensitivity was 65%, pooled specificity 66% and diagnostic odds ratio 4.74 respectively., Conclusion: This meta-analysis suggests that the accuracy of carcinoembryonic antigen in differentiating "between benign and malignant" pancreatic cysts was poor. The decision to perform surgical resection for pancreatic cystic lesions should not be based solely on carcinoembryonic antigen level., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: It was the aim of this study to examine pancreatic cyst cases that lack markedly atypical or malignant epithelium on endoscopic ultrasound-guided fine-needle aspirations., Study Design: We conducted a retrospective case review study, including 24 cases that were either acellular or lacked cytologic atypia and were subsequently resected. The cases were retrospectively divided into 3 categories: (1) non-diagnostic, (2) cyst contents only, and (3) cyst contents with bland-appearing epithelium. The cyst contents were subdivided into mucinous and non-mucinous types. The cytologic diagnoses were correlated with cyst fluid carcinoembryonic antigen (CEA) levels and subsequent histologic diagnoses., Results: Category 1 comprised 4 cases: 2 cases (CEA >800 ng/ml) with mucin-producing neoplasms and 2 cases (CEA not determined) with microcystic serous cystadenomas. Category 2 included 4 cases with non-mucinous and 4 with mucinous contents. In the first subgroup, 2 cases (CEA >800 ng/ml) showed mucinous cystic neoplasms and 2 cases (CEA negligible or not determined) pseudocysts. In the second subgroup, there were 3 cases with neoplastic mucinous cysts (1 CEA >800 ng/ml, 2 not determined) and 1 case with a lymphoepithelial cyst with mucinous metaplasia (CEA >800 ng/ml). Almost all cases (10/11) in category 3 had neoplastic mucinous cysts regardless of the CEA levels., Conclusions: The proposed 3 cytologic categories of pancreatic cystic lesion combined with cyst fluid CEA levels provide useful clinical information., (Copyright © 2012 S. Karger AG, Basel.)

Context: Pancreatic cysts are increasingly detected incidentally, many of which are premalignant. Despite EUS-FNA and CEA level measurement, the diagnosis of a premalignant cyst may remain uncertain., Case Report: We report two cases of incidentally found pancreatic cysts where initial EUS-FNA cyst aspirates yielded thin fluid with very low CEA levels. Repeat aspirations one year later revealed markedly different results (slightly viscous fluid with significantly elevated CEA levels) which prompted surgical resection in both cases. Final surgical pathology revealed mucinous cystic neoplasms., Conclusion: Pancreatic cyst fluid CEA levels may increase over time, possibly due to neoplastic progression. A heightened index of suspicion for a neoplastic cyst should remain in the appropriate patient population, despite conflicting data. In cases of initial low aspirate CEA levels, we recommend a repeat EUS-FNA at a later date to exclude a premalignant lesion.