Cyst Fluid Carcinoembryonic Antigen Research Articles

Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review

ObjectiveElevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20...

Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine-needle biopsy sampling.

Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield. The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n=6, 19%), negative for malignant cells/cyst contents (n=7, 23%), atypical cells (n=3, 10%), nonmucinous cyst (n=11, 35%), and serous cystadenoma (n=4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA.

Optimal carcinoembryonic antigen (CEA) cutoff values in the diagnosis of neoplastic mucinous pancreatic cysts differ among assays

AimPancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL...

Revisiting the Performance of Cyst Fluid Carcinoembryonic Antigen as a Diagnostic Marker for Pancreatic Mucinous Cysts: A Comprehensive 20-Year Institutional Review

Revisiting the Performance of Cyst Fluid Carcinoembryonic Antigen as a Diagnostic Marker for Pancreatic Mucinous Cysts: A Comprehensive 20-Year Institutional Review

Diagnostic features of low- and high-grade mucinous neoplasms in pancreatic cyst FNA cytology.

Pancreatic cyst cytology evaluates for neoplastic mucin and epithelial grade. This study describes cytological features of low- and high-grade mucinous neoplasms (MNs) using gastrointestinal contaminants for comparison. Histologically confirmed pancreatic cystic neoplasms were reviewed by a panel of cytopathologists to identify which, among 26 selected cytologic features, correlate significantly with low- and high-grade MN. A test for greater than or equal to four of eight high-grade features (three-dimensional architecture, high nuclear:cytoplasmic ratio, moderate nuclear membrane abnormalities, loss of nuclear polarity, hyperchromasia, >4:1 nuclear size variation in one cluster, karyorrhexis, and necrosis) was assessed for identifying a high-grade neoplasms. Additional characteristics of the cohort such as cyst fluid carcinoembryonic antigen results, molecular testing, Papanicolaou Society of Cytopathology classification, and select high-risk clinical features are described. Endoscopic ultrasound fine-needle aspirations from 134 MN and 17 serous cystadenomas containing gastrointestinal contaminants were included. The MN consisted of 112 (84%) intraductal papillary MNs (low-grade=69, 62%; high-grade=24, 21%; and invasive=19, 17%) and mucinous cystic neoplasms (low-grade=20, 90%; high-grade=2, 10%). Half had greater than five clusters of epithelium for analysis. Compared with gastrointestinal contaminants, mucin from MN was thick and colloid-like (40% vs. 6%, p < .01), covered >20% of the smear area (32% vs. none, p < .01), and contained histiocytes (46% vs. 18%, p=.04). Greater than or equal to four of eight select high-grade features was present in 36% of high-grade MN with sensitivity 37% and 98% specificity. Colloid-like features, >20% of smear, and histiocytes correlated with MN. Testing for greater than or equal to four high-grade features had low sensitivity and high specificity for high-grade MN.

Accurate Identification of Mucinous Pancreatic Cystic Lesions Using Small-Volume Analytes

IntroductionThe accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only routinely used test, requires high volumes and has low sensitivity. We aimed to compare the performance of two investigational small-volume biomarkers, glucose and the protease gastricsin, to CEA for PCL classification. MethodsWe obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs from four institutions between 2003 and 2016. Gastricsin activity was measured using an internally quenched fluorescent substrate. Glucose levels were measured with a standard glucometer. CEA levels were obtained from the medical record. Models using Classification and Regression Trees were created to predict mucinous status. Model performance was evaluated using nested cross-validation. ResultsGastricsin activity, CEA, and glucose levels from patients with mucinous (n = 50) and nonmucinous (n = 31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers (gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized [GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly improve AUC, with CEA + GVN (0.88) performing similarly to CEA + GPN (0.95), GVN + glucose (0.87), GPN + glucose (0.95), and CEA + glucose (0.84). The three-analyte combination performed similarly to single and dual classifiers (GPN + glucose + CEA AUC 0.95; GVN + glucose + CEA AUC 0.87). After multiple comparison corrections, there were no significant differences between the individual, dual, and triple classifiers. ConclusionsGastricsin and glucose performed similarly to CEA and required <5% of the volume required for CEA; these classifiers may be useful in patients with limited cyst fluid. Future multicenter prospective studies are needed to validate and compare these novel small-volume biomarkers.

S62 Benefits of Using Pancreatic Cyst Fluid Glucose in Community-Based Setting to Evaluate Pancreatic Cystic Lesions

Introduction: In the evaluation of incidental asymptomatic pancreatic cystic lesions (PCLs), it is necessary to identify mucinous cysts due to their risk for malignant transformation.1 Current guidelines recommend obtaining cyst fluid carcinoembryonic antigen (f-CEA), but this test has limitations.2 Recently, a low cyst fluid glucose level (f-Glu) < 50 mg/dl has emerged as an alternative to f-CEA.3 Methods: Patients from 11/2021-4/2022 with a PCL were retrospectively analyzed. Demographics, radiology & EUS findings, & test results were collected. f-CEA and f-Glu were ordered on each patient, with priority placed on f-CEA, followed by f-Glu. Results: 13 patients (7 M:6 F, median age 74) with PCLs were analyzed. The median cyst size was 27 mm (16.8-77 mm), and the median fluid volume obtained was 1.5 mL (0-170 mL). In our patients, both f-CEA and f-Glu were available in 46% (6/13), only f-CEA in 2/13 (15%), and only f-Glu in 3/13 (23%). In 2 patients, f-CEA/f-Glu could not be obtained. In 6 patients, when both f-CEA and f-Glu were available, there was 100% agreement between the two test results. In 5/13 cases, f-CEA could not be obtained. In 2 cases, f-Glu was the only test result that was obtained. Conclusion: Since pancreatic f-Glu has emerged as an alternative to f-CEA,3 we aimed to incorporate f-Glu in evaluating PCLs in our community-based EUS program. In our study, f-Glu did correlate with f-CEA results. Unfortunately, in a community hospital, f-CEA requires >3 mL for analysis. In contrast, f-Glu requires >1 mL, and is readily available, making it an ideal alternative to f-CEA. In our series, the median fluid volume aspirated was 1.5 mL, and in 38% of cases, f-CEA could not be obtained. In 69% of cases, f-Glu was measured despite low fluid volume (< 3 mL), making it advantageous in the evaluation of a PCL. In this limited series, f-Glu was a more favorable alternative to f-CEA in a community-based EUS program. (Table). Table 1. - Summary of Patient Characteristics and Test Results Patient Age Sex f-CEA f-Glu Cyst Size (mm) Amt of Cyst Fluid (mL) Cytology 1 78 M N/A 127 27 × 21 N/A No malignancy 2 82 M N/A < 10 70 × 50 N/A Degenerated cells 3 74 F 15.5 N/A 19 × 9 1 N/A 4 79 M N/A N/A 38 × 32 N/A Mucin and cell atypia 5 58 M 107 20 26 × 25 4.5 Inflammatory cells 6 81 F N/A N/A 33 × 23 N/A Mucin and papillary cells w/ LGD 7 74 F 789 N/A 19 × 11 1.5 N/A 8 66 M 216 < 10 21.6 × 16.8 3 No malignancy 9 55 F 29 19 58 × 65 5 No malignancy 10 84 F N/A < 10 14.8 × 16.8 1 No malignancy 11 64 M 457 < 10 22.5 × 20.4 2 Fibrovascular tissue w/ scant fragments of reactive glandular tissue 12 65 F 88,809 < 10 77 × 44 170 No malignancy 13 80 M 532 < 10 50 7 No malignancy N/A, not available.

Lower cyst fluid carcinoembryonic antigencutoff is helpful in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.

Pancreatic cystic lesions (PCLs) are being diagnosed with increased frequency and have varying neoplastic potential. We conducted this multimodal, prospective study to evaluate the role of tumor cytology and molecular markers to differentiate PCL subtypes. Consecutive undiagnosed patients with PCLs (n = 100, mean age: 50.37 years; 41% males) were prospectively studied. Cyst fluid carcinoembryonic antigen (CEA), CA19.9, CA125, CA72.4, and vascular endothelial growth factor-alpha (VEGF-α) levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA) method. Mutational analysis of the KRAS gene (exon 2, Codon 12 and 13) and GNAS gene (Exon 8, Codon 201) were performed by Sanger's sequencing. The mean cyst size was 4.32 ± 2.4 cm. Fluid cytology revealed definitive diagnosis in 21 (22.3%) patients. All malignant PCLs could be identified on cytology whereas 10/14 (71%) non-malignant mucinous PCLs could also be identified on cytology based on mucin staining. Among the tested tumor markers, cyst fluid CEA had the best diagnostic performance for differentiation between mucinous and non-mucinous PCLs (AUC 0.933 [95% CI 0.86-0.91]). At a cyst fluid CEA cutoff level of 45.0 ng/mL, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiation between mucinous and non-mucinous cysts were 88.5%, 96.8%, 92.0%, and 95.3%, respectively (p &lt; 0.05). KRAS and GNAS mutation had no significant diagnostic benefit in comparison to fluid cytology and CEA levels. Fluid CEA at a lower cutoff of 45 ng/mL is the most accurate marker to differentiate between mucinous and non-mucinous PCL. The KRAS and GNAS mutational analysis does not improve upon the diagnostic performance of fluid cytology and tumor markers.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUNDPancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIMTo evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-β), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODSThis study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTSThe mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSIONEUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

The Role of Interleukin 1 Beta in Differentiating Malignant from Benign Pancreatic Cysts.

Background and Aim: The frequency of detection of pancreatic cystic lesions (PCLs) in magnetic resonance imaging performed for reasons unrelated to the pancreas reaches up to 13.5%. The aim of this study was to evaluate the role of cyst fluid interleukin 1 beta (IL1β) and different endoscopic ultrasound (EUS) features in differentiating premalignant/malignant from benign pancreatic cysts. In addition, to evaluate the role of pancreatic cyst fluid carcinoembryonic antigen (CEA) in differentiating mucinous from nonmucinous pancreatic cysts. Methods: This study was conducted on 73 patients with PCLs. EUS-guided fine-needle aspiration (EUS-FNA) was performed on all patients. Estimation of IL1β and CEA levels in aspirated specimens were carried out. Results: Pancreatic cyst fluid IL1β level could not differentiate between premalignant/malignant and benign pancreatic cysts. At a cutoff value of 19.81 ng/mL pancreatic cyst fluid CEA has 64.3% sensitivity and 84.4% specificity in differentiating mucinous from nonmucinous pancreatic cyst. EUS can differentiate between premalignant/malignant pancreatic cysts and benign cysts with a sensitivity of 66.7%, specificity of 69.2% Conclusions: Pancreatic cyst fluid IL1β level cannot differentiate between premalignant/malignant and benign pancreatic cysts. CEA level can help in differentiation between mucinous and nonmucinous cysts. EUS can be useful in differentiation between premalignant/malignant pancreatic cysts and benign cysts.

Pancreatic cyst fluid glucose: a rapid on-site diagnostic test for mucinous cysts

Pancreatic cystic fluid (PCF) analysis is frequently used for cyst diagnosis with carcinoembryonic antigen (CEA) being the most accepted biomarker. Low glucose levels in PCF were previously suggested as a marker for mucinous cysts. A bed-side glucometer is a point-of care, immediate, simple, and cheap method which requires a small volume of PCF. The aim of our study was to identify the optimal glucose cut-off level for identifying mucinous cysts, evaluate the diagnostic accuracy of glucose compared to CEA, and validate glucometry against reference laboratory biochemical analysis. A single-center prospective cohort study. Consecutive patients aged 18 and older, who underwent pancreatic cyst evaluation, at the Tel Aviv Medical Center between 2016 and 2021 were analyzed. Cyst type was defined based on clinical, laboratory, and radiologic findings. Glucose was measured using laboratory biochemical analysis and two glucometers. Receiver operating characteristic analysis derived sensitivity, specificity, and accuracy were calculated and McNemar test was used to compare between methods. One hundred and one PCF samples were evaluated. The areas under the receiver operating characteristics curve for identifying mucinous cysts using glucometer, glucose laboratory, and their combination were 0.88 (p < 0.001), 0.92 (p < 0.001), and 0.93 (p < 0.001), respectively. A glucose level of 87 mg/dL was identified as the optimal laboratory glucose threshold value to detect mucinous cyst with a sensitivity of 90.9%, specificity of 83.3%, and accuracy of 89.3, higher in comparison to cyst fluid CEA. Furthermore, PCF glucose levels had the strongest association with mucinous cysts. Our findings suggest that PCF glucose level is more accurate than CEA for the diagnosis of mucinous cysts. Glucometry glucose level assessment demonstrated an excellent correlation with laboratory glucose measurements and may become a useful diagnostic test.

Utility of Cyst Fluid Carcinoembryonic Antigen in Differentiating Mucinous and Non-mucinous Pancreatic Cysts: An Updated Meta-Analysis.

Mucinous pancreatic cysts are considered premalignant and managed differently compared to benign pancreatic cystic lesions. The aim of this updated meta-analysis is to assess the diagnostic accuracy of cyst carcinoembryonic antigen (CEA) in differentiating between mucinous and non-mucinous pancreatic cysts. Studies comparing the diagnostic accuracy of CEA (cutoff level of 192ng/mL) in differentiating between mucinous and non-mucinous pancreatic cysts were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooled estimates of diagnostic precision were calculated using random and fixed effects models. Initial search identified 526 reference articles, of these 34 relevant articles were selected and reviewed. Data were extracted from 15 studies (n = 2063) which met the inclusion criteria. The pancreatic cystic fluid CEA level at a 192ng/mL cutoff value had pooled specificity of 88.6% (95% CI 85.9-90.9) and pooled sensitivity was found to be 60.4% (95% CI 57.7-62.9). The pooled positive likelihood ratio was 4.5 (95% CI 2.9-6.9) and the pooled negative likelihood ratio was 0.45 (95% CI 0.38-0.52). The pooled diagnostic odds ratio, the odds of having mucinous cyst with elevated CEA, was 11.4 (95% CI 6.9-18.7). ThePfor chi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. This meta-analysis suggests that the cyst fluid CEA level at a 192ng/mL cutoff value is highly specific in the diagnosis of mucinous cystic lesions with reasonable sensitivity.

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.

Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic (n = 25), non-mucinous neoplastic (n = 20), mucinous neoplastic (n = 47) and pancreatic adenocarcinomas with cystic degeneration (n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. Cyst fluid CEA and CA 19-9, levels were significantly higher (P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower (P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1ng/mL) and glucose (cut-off = 2.8mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12ng/mL) and glucose (cut-off = 2.8mmol/L) added value to prediction.

Cyst fluid metabolites distinguish malignant from benign pancreatic cysts.

OBJECTIVESCurrent standard of care imaging, cytology, or cystic fluid analysis cannot reliably differentiate malignant from benign pancreatic cystic neoplasms. This study sought to determine if the metabolic profile of cystic fluid could distinguish benign and malignant lesions, as well as mucinous and non-mucinous lesions.MethodsMetabolic profiling by untargeted mass spectrometry and quantitative nuclear magnetic resonance was performed in 24 pancreatic cyst fluid from surgically resected samples with pathological diagnoses and clinicopathological correlation.Results(Iso)-butyrylcarnitine distinguished malignant from benign pancreatic cysts, with a diagnostic accuracy of 89%. (Iso)-butyrylcarnitine was 28-fold more abundant in malignant cyst fluid compared with benign cyst fluid (P=.048). Furthermore, 5-oxoproline (P=.01) differentiated mucinous from non-mucinous cysts with a diagnostic accuracy of 90%, better than glucose (82% accuracy), a previously described metabolite that distinguishes mucinous from non-mucinous cysts. Combined analysis of glucose and 5-oxoproline did not improve the diagnostic accuracy. In comparison, standard of care cyst fluid carcinoembryonic antigen (CEA) and cytology had a diagnostic accuracy of 40% and 60% respectively for mucinous cysts. (Iso)-butyrylcarnitine and 5-oxoproline correlated with cyst fluid CEA levels (P<.0001 and P<.05 respectively). For diagnosing malignant pancreatic cysts, the diagnostic accuracies of cyst size > 3 cm, ≥ 1 high-risk features, cyst fluid CEA, and cytology are 38%, 75%, 80%, and 75%, respectively.Conclusions(Iso)-butyrylcarnitine has potential clinical application for accurately distinguishing malignant from benign pancreatic cysts, and 5-oxoproline for distinguishing mucinous from non-mucinous cysts.

ID: 3521525 DIAGNOSTIC ACCURACY OF INTRACYSTIC CONCENTRATIONS OF GLUCOSE AND CEA IN IDENTIFYING MUCIN PRODUCING CYSTIC NEOPLASMS OF THE PANCREAS: A MULTICENTER RETROSPECTIVE COHORT STUDY OF HISTOLOGICALLY-PROVEN CYSTS

Pancreatic cystic lesions (PCLs) are encountered incidentally in 2.4-19.6% of the general population and the mucinous subtypes carry malignant potential. Differentiating mucinous from non-mucinous PCLs can present a diagnostic challenge. Current guidelines recommend the use of cyst fluid carcinoembryonic antigen (CEA) to identify mucinous PCLs, however its sensitivity and specificity can vary widely. Through the needle biopsy or DNA mutational analysis have yielded favorable results but clinical applicability is limited by cost and inaccessibility. Intracystic glucose has shown promise in differentiating mucinous PCLs, but data are limited to frozen specimens and PCLs without uniform histologic diagnostic confirmation. The aim of this study was to assess the diagnostic accuracy of intracystic glucose in differentiating mucinous from non-mucinous PCLs from fresh fluid of PCLs with confirmatory histologic diagnoses.

Intracystic Glucose Levels Appear Useful for Diagnosis of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis.

Carcinoembryonic antigen (CEA) in the pancreatic cystic fluid is the most important biomarker for differentiating mucinous from non-mucinous pancreatic cystic lesions (PCLs). However, recent studies have shown that glucose levels in pancreatic cystic fluid can discriminate mucinous from non-mucinous cysts. To perform a meta-analysis to determine the utility of intracystic fluid glucose of pancreatic mucinous cysts compared with intracystic CEA. We conducted a systematic review of the literature in the PubMed, OVID Medline, and Cochrane databases. This meta-analysis considers studies published up to October 2020. Six studies comprising 506 patients were selected; 61.2% of the population was female. Of the 480 PCLs, 287 (59.7%) were mucinous. Pooled sensitivity and specificity of cystic fluid glucose levels for mucinous PCLs were 91% and 85%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 6.33 and 0.11, respectively. Pooled diagnostic odds ratio (DOR) was 60.94. The pooled area under the summary receiver operating characteristic (SROC) curve was 0.959. Pooled sensitivity and specificity of pancreatic cystic fluid CEA levels were 61% and 93%. The PLR and NLR were 8.51 and 0.40, respectively. Pooled DOR was 23.52, and the pooled area under the SROC curve was 0.861. Glucose has become a useful method and appears to be better than CEA for differentiating between mucinous PCLs and non-mucinous PCLs. We suggest that the analysis of glucose in PCLs be routinely performed for the differential diagnosis of these lesions.

Mucin Expression in Mucinous Pancreatic Cysts: Can String Sign Test Predict Mucin Types? A Single Center Pilot Study.

Mucinous pancreatic cystic lesions (PCLs) express different mucin (MUC) types according to their histomorphologic types. High cystic fluid viscosity may help in the detection of mucinous PCLs. We hypothesized that high cystic fluid viscosity may be suggestive of a certain MUC type in mucinous PCLs. Prespecified MUC types (MUC1, MUC2, MUC4, MUC5AC, and MUC6) were evaluated in 18 definitively diagnosed mucinous PCLs with sufficient tissue material and prediagnostic cyst fluid viscosity evaluation-string sign (SS)-test. We evaluated the agreement of MUC expression with positive SS test results. Later, we compared cystic fluid carcinoembryonic antigen (CEA) between the prespecified MUC expressing and nonexpressing cyst types. A total of 18 mucinous PCL patients, 11 females, with mean age ± SD (59.7 ± 13.3) were included. Almost all malignant mucinous PCLs expressed MUC1 (71.4%) (P = .023). We found no significant agreement between the prespecified MUC types and positive SS, except MUC4 which had mild agreement. Also, no significant relation was found between cystic fluid CEA levels and MUC expression (P = .584). We did not detect a significantly moderate or good agreement between the prespecified MUC types and SS test. MUC1 was highly expressed in malignant mucinous cysts; however, it was incompatible with the SS test. MUC4 expression showed mild agreement with the SS test in a small number of patients.

Cyst Fluid Carcinoembryonic Antigen Level Difference between Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms.

Background/AimsThe role of cyst fluid carcinoembryonic antigen (CEA) level in differentiating mucinous pancreatic cystic lesions (PCLs) is controversial. We investigated the role of cyst fluid CEA in differentiating low-risk (LR)-intraductal papillary mucinous neoplasms (IPMNs) from high-risk (HR)-IPMNs and LR-mucinous cystic neoplasms (MCNs). MethodsThis was a retrospective study of 466 patients with PCLs who underwent endoscopic ultrasound-guided fine-needleaspiration over a 7-year period. On histology, low-grade dysplasia and intermediate-grade dysplasia were considered LR, whereas high-grade dysplasia and invasive carcinoma were considered HR. ResultsData on cyst fluid CEA levels were available for 50/102 mucinous PCLs with definitive diagnoses. The median CEA (range) levels were significantly higher in HR cysts than in LR cysts (2,624 [0.5–266,510] ng/mL vs. 100 [16.8–53,445]ng/mL, p=0.0012). The area under the receiver operating characteristic curve (AUROC) was 0.930 (95% confidence interval [CI], 0.5–0.8; p<0.001) for differentiating LR-IPMNs from LR-MCNs. The AUROC was 0.921 (95% CI, 0.823–1.000; p<0.001) for differentiating LR-IPMNs from HR-IPMNs. Both had a CEA cutoff level of >100ng/mL, with a negative predictive value (NPV) of 100%. ConclusionsCyst fluid CEA levels significantly vary between LR-IPMNs, LR-MCNs, and HR-IPMNs. A CEA cutoff level of >100ng/mL had a 100% NPV in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

EUS is accurate in characterizing pancreatic cystic lesions; a prospective comparison with cross-sectional imaging in resected cases

BackgroundImaging modalities for characterizing pancreatic cystic lesions (PCLs) is a known uncertainty. The aim of this prospective study was to compare the diagnostic performance of endoscopic ultrasound morphology, cytology and cyst fluid carcinoembryonic antigen (EUS-FNA-CEA) with cross-sectional imaging in resected PCLs. MethodsThe cross-sectional imaging and EUS-FNA-CEA results were collected in an academic tertiary referral centre using histology of the surgical specimen as the diagnostic standard. ResultsOf 289 patients undergoing evaluation for PCL with cross-sectional imaging and EUS-FNA between February 2007 and March 2017, 58 underwent surgical resection providing a final diagnosis of the PCLs: 45 mucinous, 5 serous, 1 pseudocyst, 2 endocrine, 2 solid pseudopapillary neoplasms and 3 other. EUS-FNA-CEA was more accurate than cross-sectional imaging in diagnosing mucinous PCLs (95% vs. 83%, p = 0.04). Ninety-two percent of the PCLs with high-grade dysplasia or adenocarcinoma were smaller than 3 cm in diameter. The sensitivity of EUS-FNA-CEA and cross-sectional imaging for detecting PCLs with high-grade dysplasia or adenocarcinoma were 33% and 5% (p = 0.03), respectively. However, there was no difference in accuracy between the modalities (62% vs. 66%, p = 0.79). The sensitivity for detecting pancreatic adenocarcinomas only was 64% for EUS-FNA-CEA and 9% for cross-sectional imaging (p = 0.03). Overall, EUS-FNA-CEA provided a correct diagnosis in more patients with PCLs than cross-sectional imaging (72% vs. 50%, p = 0.01).ConclusionsEUS-FNA-CEA is accurate and should be considered a complementary test in the diagnosis of PCLs. However, the detection of PCLs with high-grade dysplasia or adenocarcinoma needs to be improved. Cyst size does not seem to be a reliable predictor of high-grade dysplasia or adenocarcinoma.

S0085 Technical Feasibility and Diagnostic Yield of EUS-Guided Through-the-Needle Biopsy Forceps for Pancreatic Cystic Lesions: Experience of a Tertiary Referral Center

INTRODUCTION: Current management of pancreatic cystic lesions (PCLs) is based on clinical presentation, imaging, and cyst fluid analysis. Nevertheless, a PCL may remain a diagnostic challenge after completion of all standard investigations. Recently, through-the-needle biopsy (TTNB) sampling was added to the armamentarium for PCL evaluation during endoscopic ultrasound (EUS). METHODS: We carried out a prospective cohort study to evaluate the feasibility, diagnostic yield and safety of EUS-TTNB. Technical success was defined as visible specimen present after TTNB sampling. Clinical success was determined by the pathology results whenever the cyst wall lining was present, and a histologic diagnosis could be established. RESULTS: A total of 20 patients (mean age 62.0 ± 11 years; 14 (61%) females) were included. The median cyst diameter was 29.5 mm (IQR 21.3–56.8 mm, range 15–75 mm). The procedure was technically successful in 19 patients (95%). TTNB allowed a histologic diagnosis in 15 out of 19 cases (clinical success: 78.9%). Fine-needle aspiration (FNA) cytology was performed in 19/20 patients but was nondiagnostic in 9 cases (45%). The combination of fluid cytology with TTNB resulted in an increased overall diagnostic yield (17/20 cases, 85%), providing additional information in 2 cases in which TTNB results were inconclusive. While cyst fluid carcinoembryonic antigen CEA >192 ng/mL was found in 5/20 cases, TTNB allowed the diagnosis of 12 mucinous lesions. Based on histological features and immunochemical mucin expression on TTNB samples, we were able to determine the predominant phenotype of IPMN in 8/10 cases. Surgical specimens were available in 9 cases with a diagnostic concordance rate of 66.7% (6/9 cases) when compared with TTNB specimens. Overall, in 7 cases, TTNB provided the diagnosis otherwise not suggested by cytology. Also, the histologic features of TTNB specimens changed the presumable diagnosis of the PCL in 5/20 cases and changed management in 8/20 patients (40%). Adverse events occurred in one patient who developed self-limited intracystic bleeding. CONCLUSION: EUS-TTNB was associated with high technical and clinical success and low adverse events rate. It was found superior to FNA cytology and cyst fluid CEA. The addition of TTNB to the current standard approach may provide an incremental benefit for PCLs diagnosis and risk stratification. Also, the possibility for IPMN subtyping can become an important feature for patient management.