Search

Background and Aims: Recently, low levels of intracystic glucose acquired with EUS-guided pancreatic cyst fluid sampling have been shown to help to differentiate mucinous from nonmucinous cystic neoplasms. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic characteristics of pancreatic cyst fluid glucose compared with carcinoembryonic antigen (CEA) for pancreatic cystic lesions., Methods: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines and meta-analysis analyzed according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve for intracystic glucose or CEA alone or combination testing., Results: Eight studies (609 lesions; mean patient age, 63.56 ± 2.75 years; 60.36% women) were included. The pooled sensitivity for pancreatic cyst fluid glucose was significantly higher compared with CEA alone (91% [95% confidence interval {CI}, 88-94; I 2  = .00] vs 56% [95% CI, 46-66; I 2  = 537.14]; P < .001) with no difference in specificity (86% [95% CI, 81-90; I 2  = 24.16] vs 96% [95% CI, 90-99; I 2  = 38.06]; P > .05). Diagnostic accuracy was significantly higher for pancreatic cyst fluid glucose versus CEA alone (94% [95% CI, 91-96] vs 85% [95% CI, 82-88]; P < .001). Combination testing with pancreatic cyst fluid glucose and CEA did not improve the diagnostic accuracy compared with glucose alone (97% [95% CI, 95-98] vs 94% [95% CI, 91-96]; P > .05)., Conclusions: Low pancreatic cyst fluid glucose was associated with a high sensitivity and specificity with significantly improved diagnostic accuracy compared with CEA alone for the diagnosis of mucinous versus nonmucinous pancreatic cystic lesions., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Pancreatic cystic fluid (PCF) analysis is useful to distinguish between different cyst types and to guide management. The aim of our study was to compare the diagnostic accuracy of glucose level with carcinoembryonic antigen (CEA) in PCF for mucinous cyst diagnosis., Methods: We identified studies with PCF obtained by EUS before surgery, with cysts classified as mucinous and nonmucinous according to surgical specimens. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic (ROC) curve analysis were conducted., Results: For CEA, we included 31 studies with 5268 patients, of which 2083 were referred for surgery. For glucose, we included 4 studies with 345 patients, of which 275 were referred for surgery. Glucose performed better than CEA for mucinous cysts diagnosis (premalignant and malignant) with sensitivities of .90 (95% confidence interval [CI], .85-.94) and .67 (95% CI, .65-.70), specificities of .82 (95% CI, .72-.89) and .80 (95% CI, 0.76-0.83), and areas under the ROC curve of .96 and .79, respectively. Glucose had a higher sensitivity (90%), with uncommon false-negative results, making it an excellent biomarker to exclude a mucinous cyst. Sensitivity analysis demonstrated that the findings of the current meta-analysis are robust., Conclusion: Glucose level in PCF is more accurate than CEA for preoperative diagnosis of mucinous cysts. It may become a useful first-line test, particularly in small cysts with a limited volume of PCF. Larger studies are awaited to confirm glucose as the single test for mucinous cyst diagnosis., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs)., Methods: Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI)., Results: Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I 2  = 86.74%), 91% (95% CI, 72-98; I 2  = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001)., Conclusions: Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Through-the-needle microforceps are a recent addition to the EUS armamentarium for evaluation of pancreatic cystic lesions (PCLs). The main aim of this study was to assess the technical feasibility, diagnostic yield, and safety of EUS-guided microforceps biopsy for PCLs., Methods: Our electronic endoscopy database was queried to identify patients who underwent EUS-guided FNA (EUS-FNA) of PCLs and microforceps biopsies during the same procedure. A biopsy was done on the wall of the cyst with the microforceps through the 19-gauge needle, and cyst fluid was collected for cytology and carcinoembryonic antigen (CEA) levels. Adverse events were recorded per published American Society for Gastrointestinal Endoscopy criteria., Results: Twenty-seven patients underwent EUS-FNA and microforceps biopsy of PCLs from February 2016 to July 2017. Fourteen cysts were located in the pancreatic head and/or uncinate, and 13 were located in the body and/or tail region. Microforceps biopsies were technically successful in all cases and provided a pathology diagnosis in 24 of 27 cases (yield 88.9%). Microforceps biopsies diagnosed mucinous cyst in 9 patients (33.3%), serous cystadenoma in 4 (14.8%), neuroendocrine tumor in 1 (3.7%), and benign and/or inflammatory cyst in 10 (37.1%). In 7 patients (26%), microforceps biopsy results drastically changed the diagnosis, providing diagnoses otherwise not suggested by cytology or cyst fluid CEA levels. However, cytology provided a diagnosis of mucinous cyst in 4 cases (14.8%) not detected by microforceps biopsies. No adverse events were noted., Conclusion: Microforceps biopsies were associated with high technical success, and an excellent safety profile and may be a useful adjunctive tool, complementing existing EUS-FNA sampling protocols for PCLs., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Advances in imaging technology have improved the annual detection rate of pancreatic cystic lesions (PCLs), but the preoperative diagnosis of PCLs remains unclear. Thus, the usefulness of single-operator cholangioscopy (SOC) as a diagnostic imaging tool for PCLs is worth investigating. We performed an intracystic visual examination of PCLs using SOC to determine the diagnostic value of SOC for PCLs., Methods: In this retrospective observational study, PCLs were confirmed using a diagnostic imaging modality. Patients who underwent an EUS-guided through-the-needle fiberoptic pancreatic cystoscopy and SOC examination and those whose lesion type was definitively diagnosed were included (n = 43). If the cystic fluid was turbid, a physiologic saline solution was injected into the cyst, and a SOC fiberoptic probe was inserted through a 19-gauge needle to observe the wall of the intracystic cavity and its contents. The characteristics were recorded, and the cystic fluid and biopsy specimens were further assessed by performing liquid-based cytologic and histopathologic examinations. Particularly, histopathologic examinations were performed in patients who underwent surgery., Results: Intracystic characteristics of the confirmed cases of PCLs (43 patients) were identified through intracystic visual examination with SOC. The clarity of cyst fluid is a prerequisite for imaging by SOC. The tree-like branching pattern of blood vessel distribution may be a serous cystic neoplasm-specific characteristic. Intracystic papilla-like structure is an important characteristic for diagnosing mucinous cystic neoplasms., Conclusions: The identified imaging characteristics such as blood vessel distribution on the intracystic wall and the contents of different PCLs observed under the SOC probe can provide useful information for diagnosing PCLs. SOC could be an important ancillary imaging test of PCLs by EUS., (Copyright © 2017. Published by Elsevier Inc.)

Background and Aims: The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study was to evaluate morphologic, cytologic, and change in cyst fluid DNA after PCA., Methods: In a prospective single-center study, consecutive patients with suspected benign 10- to 50-mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis, and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete response (CR), partial response, or persistent, with <5%, 5% to 25%, and 25% of the original cyst volume, respectively., Results: Thirty-six patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28), and CR occurred in 19 patients (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, increased or appearance of macrophages in 24%, and inflammatory cells in 15%. Postablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytologic features. In the CR group, mean DNA quantity was significantly increased after ablation (P = .023) without a change in quality (P = .136)., Conclusions: EUS-PCA induces morphologic and cytologic changes of pancreatic cysts, none of which appears to predict overall imaging-defined response to ablation. (Clinical trial registration numbers: NCT00233038 and NCT01643460.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

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 (R 2  = 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., (Copyright © 2016. Published by Elsevier Inc.)

Background: Diagnosis of mucinous pancreatic cysts (MPCs) is challenging due to the poor sensitivity of cytology provided by EUS-guided-FNA (EUS-FNA)., Objective: To quantify the test characteristics of molecular (DNA) analysis in suspected low-risk MPCs., Design: A prospective cohort study performed in between 2008 and 2011., Setting: Academic referral center., Patients: Consecutive patients who underwent EUS-FNA of suspected MPCs., Intervention: EUS-FNA and molecular (DNA) analysis of cyst fluid., Main Outcome Measurements: The sensitivity and specificity of molecular analysis in the diagnosis of MPCs using the criterion standard of surgical pathology in resected cysts., Results: Patients with suspected MPCs underwent EUS-FNA and cyst fluid DNA analysis. Surgical resection was performed in 48 patients (17%), confirming a mucinous pathology in 38 (79%). In this group, molecular analysis had a sensitivity of 50% and a specificity of 80% in identifying MPCs (accuracy of 56.3%). The combination of molecular analysis with cyst fluid carcinoembryonic antigen (CEA) and cytology resulted in higher MPC diagnostic performance than either one of its individual components, with a sensitivity, specificity, and accuracy of 73.7%, 70%, and 72.9%, respectively. There was no significant difference in accuracy between molecular analysis and CEA/cytology in this group., Limitations: Single-center experience., Conclusion: Molecular analysis aids in the diagnosis of MPCs when cytology is nondiagnostic or cyst fluid is insufficient for CEA or its level is indeterminate. Our results do not support the routine use of molecular analysis, which should be used selectively after review of imaging findings and cyst fluid studies. Further studies are needed to assess DNA's performance in malignant cysts., (Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

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.

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.

Background: Benign pancreatic serous cystadenoma usually is morphologically distinguishable from mucinous cystadenomas, which require resection because of their malignant potential. A macrocystic variant of serous cystadenoma recently has been described, rendering this important distinction more difficult. The aim of this study was to determine the EUS and tumor marker characteristics of mucinous cystadenoma compared with macrocystic serous cystadenomas., Methods: Medical records for consecutive patients seen between 1995 and 2002, with a histopathologic diagnosis of mucinous cystadenoma or macrocystic serous cystadenoma after surgery, who had undergone a detailed EUS examination, including EUS-guided FNA, were retrospectively reviewed., Results: A resection specimen was available for 32 mucinous cystadenomas and 9 macrocystic serous cystadenomas. No significant differences were observed with regard to clinical data (age, gender, presence of symptoms), lesion size, and location within the pancreas. All mucinous cystadenomas had a discernible cyst wall (thickened, 66%; focal parietal nodules, 25%) compared with 56% of macrocystic serous cystadenomas (p<0.0001). A thick echo content also was more frequent in mucinous cystadenoma (56% vs. 11%; p=0.04; statistical significance removed by the Bonferroni correction). Microcysts were only observed in macrocystic serous cystadenomas (44%; p=0.0008). The combination of a cyst wall that is thickened and the absence of microcysts had a sensitivity of 100% and specificity of 78% for the diagnosis of mucinous cystadenoma compared with macrocystic serous cystadenoma. Although intracystic carbohydrate-associated antigen 72-4 and mucins M1 were non-discriminatory, low carcinoembryonic antigen (<5 ng/mL) and carbohydrate-associated antigen 19-9 (<50,000 U/mL) values were found in macrocystic serous lesions (respectively, 100% and 100%; p=0.0002 and p=0.0002)., Conclusions: Although there is considerable overlap, helpful EUS characteristics that differentiate mucinous cystadenoma from macrocystic serous cystadenoma include a thick cyst wall and microcysts. These features, coupled with analysis of aspirated fluid for tumor markers (especially carcinoembryonic antigen), should help to confirm the diagnosis.