Non-mucinous Pancreatic Cystic Lesions Research Articles

Glucose and lactate levels are lower in EUS-aspirated cyst fluid of mucinous vs non-mucinous pancreatic cystic lesions

BackgroundDistinguishing 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. AimsTo compare the diagnostic accuracy of intracystic glucose and CEA levels in a large cohort and explore lactate levels as potential marker. MethodsPCNs≥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. Results169 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. ConclusionIntracystic 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.

Deep-Learning-Enabled Computer-Aided Diagnosis in the Classification of Pancreatic Cystic Lesions on Confocal Laser Endomicroscopy.

Accurate classification of pancreatic cystic lesions (PCLs) is important to facilitate proper treatment and to improve patient outcomes. We utilized the convolutional neural network (CNN) of VGG19 to develop a computer-aided diagnosis (CAD) system in the classification of subtypes of PCLs in endoscopic ultrasound-guided needle-based confocal laser endomicroscopy (nCLE). From a retrospectively collected 22,424 nCLE video frames (50 videos) as the training/validation set and 11,047 nCLE video frames (18 videos) as the test set, we developed and compared the diagnostic performance of three CNNs with distinct methods of designating the region of interest. The diagnostic accuracy for subtypes of PCLs by CNNs with manual, maximal rectangular, and U-Net algorithm-designated ROIs was 100%, 38.9%, and 66.7% on a per-video basis and 88.99%, 73.94%, and 76.12% on a per-frame basis, respectively. Our per-frame analysis suggested differential levels of diagnostic accuracy among the five subtypes of PCLs, where non-mucinous PCLs (serous cystic neoplasm: 93.11%, cystic neuroendocrine tumor: 84.31%, and pseudocyst: 98%) had higher diagnostic accuracy than mucinous PCLs (intraductal papillary mucinous neoplasm: 84.43% and mucinous cystic neoplasm: 86.1%). Our CNN demonstrated superior specificity compared to the state-of-the-art for the classification of mucinous PCLs (IPMN and MCN), with high specificity (94.3% and 92.8%, respectively) but low sensitivity (46% and 45.2%, respectively). This suggests the complimentary role of CNN-enabled CAD systems, especially for clinically suspected mucinous PCLs.

Accuracy and agreement of a large panel of endosonographers for endomicroscopy-guided virtual biopsy of pancreatic cystic lesions

BackgroundAlthough emerging data evidences that EUS-guided needle-based confocal laser endomicroscopy (nCLE) accurately diagnoses pancreatic cystic lesions (PCLs), there are a lack of interobserver agreement (IOA) studies utilizing reference histopathological diagnosis and for specific PCL subtypes. Hence, we sought to assess the IOA, intra-observer reliability (IOR), and diagnostic performance of EUS-nCLE using a large cohort of patients with histopathological diagnosis amongst a broad panel of international observers. MethodsEUS-nCLE videos (n = 76) of subjects with PCLs [intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystadenoma (SCA), pseudocyst, and cystic-neuroendocrine tumors/solid pseudopapillary neoplasm (cystic-NET/SPN)], simulating clinical prevalence rates were obtained from 3 prospective studies. An international panel of 13 endosonographers with nCLE experience, blinded to all PCL data, evaluated the video library twice with a two-week washout for PCL differentiation (mucinous vs. non-mucinous) and subtype diagnosis. ResultsThe IOA (κ = 0.82, 95% CI 0.77–0.87) and IOR (κ = 0.82, 95% CI 0.78–0.85) were “almost perfect” to differentiate mucinous vs. non-mucinous PCLs. For PCL subtype, IOA was highest for SCA (almost perfect; κ = 0.85), followed by IPMN (substantial, κ = 0.72), and cystic-NET/SPN (substantial, κ = 0.73). The IOA was moderate for MCN (κ = 0.47), and pseudocyst (κ = 0.57). Compared to histopathology, observers differentiated mucinous vs. non-mucinous PCLs with high accuracy (94.8%, 95% CI 93.3–96.1). For detecting specific PCLs subtypes, EUS-nCLE was highly accurate in diagnosing non-mucinous cysts (SCA: 98%; cystic-NET/SPN: 96%; pseudocyst: 96%) and slightly less accurate for mucinous lesions (IPMN: 86%; MCN: 84%). ConclusionDiagnosis of PCLs by EUS-nCLE guided virtual biopsy is very accurate and reliable for the most prevalent pancreatic cysts in clinical practice.

Deep Learning for Automatic Differentiation of Mucinous versus Non-Mucinous Pancreatic Cystic Lesions: A Pilot Study

Endoscopic ultrasound (EUS) morphology can aid in the discrimination between mucinous and non-mucinous pancreatic cystic lesions (PCLs) but has several limitations that can be overcome by artificial intelligence. We developed a convolutional neural network (CNN) algorithm for the automatic diagnosis of mucinous PCLs. Images retrieved from videos of EUS examinations for PCL characterization were used for the development, training, and validation of a CNN for mucinous cyst diagnosis. The performance of the CNN was measured calculating the area under the receiving operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. A total of 5505 images from 28 pancreatic cysts were used (3725 from mucinous lesions and 1780 from non-mucinous cysts). The model had an overall accuracy of 98.5%, sensitivity of 98.3%, specificity of 98.9% and AUC of 1. The image processing speed of the CNN was 7.2 ms per frame. We developed a deep learning algorithm that differentiated mucinous and non-mucinous cysts with high accuracy. The present CNN may constitute an important tool to help risk stratify PCLs.

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 < 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.

Quantitative MRI of Pancreatic Cystic Lesions: A New Diagnostic Approach

The commonly used magnetic resonance (MRI) criteria can be insufficient for discriminating mucinous from non-mucinous pancreatic cystic lesions (PCLs). The histological differences between PCLs’ fluid composition may be reflected in MRI images, but cannot be assessed by visual evaluation alone. We investigate whether additional MRI quantitative parameters such as signal intensity measurements (SIMs) and radiomics texture analysis (TA) can aid the differentiation between mucinous and non-mucinous PCLs. Fifty-nine PCLs (mucinous, n = 24; non-mucinous, n = 35) are retrospectively included. The SIMs were performed by two radiologists on T2 and diffusion-weighted images (T2WI and DWI) and apparent diffusion coefficient (ADC) maps. A total of 550 radiomic features were extracted from the T2WI and ADC maps of every lesion. The SIMs and TA features were compared between entities using univariate, receiver-operating, and multivariate analysis. The SIM analysis showed no statistically significant differences between the two groups (p = 0.69, 0.21–0.43, and 0.98 for T2, DWI, and ADC, respectively). Mucinous and non-mucinous PLCs were successfully discriminated by both T2-based (83.2–100% sensitivity and 69.3–96.2% specificity) and ADC-based (40–85% sensitivity and 60–96.67% specificity) radiomic features. SIMs cannot reliably discriminate between PCLs. Radiomics have the potential to augment the common MRI diagnosis of PLCs by providing quantitative and reproducible imaging features, but validation is required by further studies.

Recent advances in the diagnostic evaluation of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.

Needle-based confocal endomicroscopy in the discrimination of mucinous from non-mucinous pancreatic cystic lesions.

BACKGROUNDPancreatic cystic lesions (PCLs) are considered a precursor of pancreatic cancer. Needle-based confocal endomicroscopy (nCLE) is an imaging technique that enables visualization of the mucosal layer to a micron resolution. Its application has demonstrated promising results in the distinction of PCLs. This study evaluated the utility of nCLE in patients with indeterminate PCLs undergoing endoscopic ultrasound fine-needle aspiration (EUS-FNA) to distinguish mucinous from non-mucinous lesions.AIMTo evaluate the accuracy of nCLE in indeterminate PCLs undergoing EUS-FNA to distinguish mucinous from non-mucinous lesions.METHODSPatients who required EUS-FNA between 2015 and 2017 were enrolled prospectively. During EUS-FNA, confocal imaging, analyses of the tumor markers carcinoembryonic antigen and amylase, and cytologic examination were conducted. All patients were followed for at least 12 mo and underwent laboratory testing and computed tomography scanning or magnetic resonance imaging. nCLE videos were independently reviewed by 6 observers to reach a final diagnosis (mucinous vs non-mucinous) based on criteria derived from previous studies; if there was disagreement > 20%, a final diagnosis was discussed after consensus re-evaluation. The sensitivity, specificity, and accuracy of nCLE were calculated. Adverse events were recorded.RESULTSFifty-nine patients were included in this study. Final diagnoses were derived from surgery in 10 patients, cytology in 13, and imaging and multidisciplinary team review in 36. Three patients were excluded from final diagnosis due to problems with nCLE acquisition. Fifty-six patients were included in the final analysis. The sensitivity, specificity, and accuracy of nCLE were 80% [95% confidence interval (CI): 65-90], 100% (95%CI: 72-100), and 84% (95%CI: 72-93), respectively. Post-procedure acute pancreatitis occurred in 5%.CONCLUSIONEUS-nCLE performs better than standard EUS-FNA for the diagnosis of indeterminate PCL.

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.

Confocal Laser Endomicroscopy Interpretation and Differentiation of Pancreatic Cysts: A Randomized Trial of Teaching Modalities

ABSTRACT Background EUS-guided needle-based confocal laser endomicroscopy (nCLE) has not been widely adopted for the differentiation of pancreatic cystic lesions (PCLs), perhaps due to a perceived difficulty in learning novel CLE image patterns. Hence, we sought to investigate the optimal teaching modality for interpretation of nCLE imaging from PCLs. Methods Sixteen nCLE-naive observers blinded to clinical data were randomized into didactic (classroom-based) versus self-directed (computer-based) teaching groups to review nCLE videos and differentiate mucinous and non-mucinous PCLs. The study was conducted concurrently for both groups in 3 phases. Phase-1-Teaching: both groups received an overview of EUS-nCLE of PCLs. Phase-2-Training: assessment of 20 EUS-nCLE subject-videos; the didactic group had a feedback session with an nCLE expert while the self-directed group received this information via pre-recorded presentation. Phase-3-Testing: assessment of 50 EUS-nCLE subject-videos. Results For all observers (n = 16), the diagnostic accuracy for nCLE-based differentiation of mucinous from non-mucinous PCLs was higher (p=0.005) in the Phase-3-Testing (94.6%, 95%CI: 92-96%) than in Phase-2-Training (89.9%, 95%CI: 85-93%). During Phase-3-Testing, both the didactic and self-directed teaching groups achieved a comparable (p=0.48) diagnostic accuracy of 93.9% and 95.4%, respectively. The interobserver agreement (kappa, standard error) for the differentiation of mucinous from non-mucinous PCLs improved from Phase-2-Training to Phase-3-Testing stage, and was “substantial” for both the didactic (k=0.81, 0.03) and self-directed (k=0.79, 0.03) training groups. Conclusion Notwithstanding didactic and self-directed teaching, a ‘training’ and ‘test’ strategy accomplished high diagnostic accuracies and considerable interobserver agreement among naive observers for EUS-nCLE image differentiation of PCLs; Clinical trial NCT02516488 ( https://clinicaltrials.gov/ct2/show/NCT02516488 )

Sa1443 CYST FLUID CARCINOEMBRYONIC ANTIGEN DIFFERENCE AMONG MUCINOUS CYSTIC NEOPLASMS AND INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS

Cyst fluid carcinoembryonic antigen (CEA) is a useful marker for differentiating between mucinous from nonmucinous pancreatic cystic lesions (PCLs). However, the role of cyst fluid CEA levels in differentiation between mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) as well as between the low risk (LR) and high risk (HR) mucinous lesions are scanty. We aimed to analyse this subject. This was a retrospective study of 52 patients with mucinous PCls diagnosed by cyto/histo-pathology out of 466 patients who underwent endoscopic-ultrasonography-guided fine-needle aspiration for PCLs over a seven-year period. On histology, low- and intermediate-grade dysplasia were considered as LR, and high-grade dysplasia and invasive carcinoma were considered as HR. Cyst fluid CEA was available for 52/102 mucinous and 44/121 nonmucinous PCLs with definitive diagnoses. The median cyst fluid CEA [Range] values were significantly higher in mucinous compared with nonmucinous cysts (1079 ng/mL [0.5-266510 ] versus 6 ng/mL [0.2-309]), and LR-MCNs compared with LR-IPMNs (7954.7 ng/mL, [299.6-53445] versus 51.3 ng/mL [16.8-132.2]), and HR-IPMNs compared with LR-IPMNs (2624 ng/mL [0.5-266510] versus 100 ng/mL [16.8-53445]). The AUROC was 0.930 (95% confidence interval [CI]: 0.5-0.8) to differentiate between LR-IPMNs and LR-MCNs and 0.921 (95% CI: 0.823-1.000) to differentiate between LR-IPMNs and HR-IPMNs using cyst fluid CEA. Both showed cutoff values of >100 ng/mL and demonstrated a sensitivity of 100/100, specificity of 75/75, and positive and negative predictive values of 66.7/78.9 and 100/100, respectively. Cyst fluid CEA is useful in differentiation between LR-MCNs from LR-IPMNs and LR-IPMNs from HR-IPMNs. Diagnosis using a cyst fluid CEA cutoff value of 100 ng/mL showed a 100% negative predive value in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

Genetic markers and confocal endomicroscopy as diagnostic approaches for pancreatic cystic lesion

Background: Preoperative diagnosis of cystic lesions of the pancreas, which can be inflammatory or proliferative, continue to present clinicians with significant clinical challenges due to the heterogeneity of the pathological processes involved. Although malignant transformation in these lesions is unusual, the opportunity for curative surgery makes identification of suitable patients essential. This requires diagnostic approaches that are up to date and evidence based. Improved diagnostic accuracy will also ensure that unnecessary surgical procedures and the associated morbidity are avoided. Methods: In this abstract we present the Results of a review of recent diagnostic approaches for pancreatic cystic lesions (PCLs). Results: Genetic sequencing allows specific mutations to be identified including the genetic profiles associated with common PCLs. This provides a potential opportunity to determine changes that indicate the progression to malignant lesions. In this respect there is increasing interest in novel cyst fluid biomarkers and their potential to differentiate between mucinous and non-mucinous PCLs. A number of mutations have been found to be associated with the main types of PCLs and these are shown in Table 1. Confocal laser endomicroscopy (CLE) is another novel diagnostic technique which allows in vivo, real time microscopy during endoscopic procedures. CLE allows for the evaluation of histology with high resolution imaging and obviates the need for a biopsy. Conclusion: There is a need to identify diagnostic Methods or combinations of Methods that will allow us to more accurately identify PCLs at risk of malignant transformation or those where it has already occurred but patients may still benefit from potentially curative surgery. There is clearly a need for a comprehensive, standardised algorithm for the diagnosis and management of PCLs utilising all the currently available diagnostic modalities.

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions

Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis. We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis. The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria. In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.

Su1347 Endoscopic Ultrasonography-Guided Needle Based Confocal Laser Endomicroscopy Has Improved Accuracy Compared to the Current Standard of Care for Differentiating Mucinous From Non-Mucinous Pancreatic Cystic Lesions

Su1347 Endoscopic Ultrasonography-Guided Needle Based Confocal Laser Endomicroscopy Has Improved Accuracy Compared to the Current Standard of Care for Differentiating Mucinous From Non-Mucinous Pancreatic Cystic Lesions

Endoscopic ultrasonography-guided needle-based confocal laser endomicroscopy has improved accuracy compared to the current standard of care for differentiating mucinous from nonmucinous pancreatic cystic lesions

Background and Objectives:Endoscopic ultrasonography (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) patterns for diagnosing mucinous pancreatic cystic lesions (PCLs) have been recently validated. The aim of this study was to compare the accuracy of EUS-nCLE to the standard of care for differentiating mucinous from nonmucinous PCLs.Methods:In a prospective study evaluating EUS-nCLE, fluid from 59 PCLs was analyzed by carcinoembryonic antigen (CEA), cytology, and next generation sequencing (NGS). The final diagnosis of PCLs was based on surgical histopathology (n = 36 [61%]) or clinical diagnosis based on imaging features, specific NGS results, follow-up >1 year, and/or resolution of PCL (n = 23 [39%]). Diagnostic indices and area under receiver operator curve (ROC) of different modalities were computed for all subjects.Results:Among the 59 subjects (31 females; mean age 59.4 years), 36 cysts were mucinous and 23 nonmucinous. The ROC analyses associated with the detection of patterns of “epithelial bands/papillae” for mucinous PCLs demonstrated the greatest area under the curve (96%). The sensitivity, specificity, and accuracy of nCLE were significantly greater than the accuracy of CEA, cytology, and combination of CEA/cytology (P < 0.001). When the study population was restricted to those with surgical histopathology (n = 36; mucinous 26 [72%]), diagnostic accuracy of nCLE for mucinous PCLs continued to be higher than the combination of CEA/cytology (94% vs. 67%, P = 0.006).Conclusions:Among the current diagnostic modalities, EUS-nCLE detection of “epithelial bands or papillae” is more accurate than the current “standard of care” for the differentiation of mucinous from nonmucinous PCLs. These preliminary results warrant further validation in larger, multicenter studies.

Needle Based Confocal Laser Endomicroscopy Can Reliably Distinguish Mucinous from Nonmucinous Pancreatic Cystic Lesions: An International External Inter-and Intra-observer Study: 2016 ACG Category Award (Biliary/Pancreas)

Needle Based Confocal Laser Endomicroscopy Can Reliably Distinguish Mucinous from Nonmucinous Pancreatic Cystic Lesions: An International External Inter-and Intra-observer Study: 2016 ACG Category Award (Biliary/Pancreas)

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions.

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (n = 6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94 %, 82 %, and 89 %, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κ = 0.67, 95 %CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κ = 0.78 ± 0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κ = 0.63; IOR κ = 0.76 ± 0.11), bright particles on a dark background of pseudocysts (IOA κ = 0.71; IOR κ = 0.78 ± 0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κ = 0.62; IOR κ = 0.68 ± 0.20). Three (6.1 % of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events.Study registration: NCT02516488

S1292 Role of EUS-FNA Based Cytology in Differentiating Mucinous Versus Non-Mucinous Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis

S1292 Role of EUS-FNA Based Cytology in Differentiating Mucinous Versus Non-Mucinous Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis

S1296 Identifying IPMN and Pancreatic Cyst That Develop Conventional Pancreatic Cancer

based cytology in differentiating mucinous versus nonmucinous PCL. Methods: MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases were used to identify studies in which results of EUS-FNA based cytology of a pancreatic cyst were compared with the results of an acceptable criterion standard, including surgical biopsy or surgical excision histology of a pancreatic cyst. Two independent reviewers extracted the standardized data. The DerSimonian-Liard random effects model was used to estimate the pooled sensitivity, specificity, likelihood, and diagnostic odds ratio (DOR). A summary receiver operating characteristic (SROC) curve was also constructed. All potential sources of heterogeneity amongst the studies were explored by subgroup and meta-regression analyses. Results: A total of 701 patients with EUS-FNA cytology of PCL were examined from 14 distinct studies that satisfied our inclusion criteria. The pooled sensitivity of EUS-FNA based cytology in diagnosing mucinous cystic lesions (MCL) was 0.65 (95% CI, 0.59-0.70) and pooled specificity was 0.92 (95% CI, 0.89-0.95). The positive likelihood ratio for diagnosing MCL by EUS-FNA based cytology was 4.93 (95% CI, 1.35-18.08) and the negative likelihood ratio was 0.46 (95% CI, 0.27-0.80). The area under the curve (AUC) was 0.87. The P value for X2 heterogeneity for all the pooled estimates was >.05 suggesting significant heterogeneity amongst the studies. Heterogeneity is probably caused by factors that were inadequately reported in primary studies and, therefore, could not be explored in this meta-analysis. Conclusion: EUS-FNA based cytology has overall low sensitivity but excellent specificity in differentiating mucinous versus non-mucinous pancreatic cystic lesions. Thus EUS-FNA based cytology should be the investigation of choice to exclude the possibility of mucinous cystic lesion while evaluating pancreatic cystic lesions. The combine role of EUS morphology, FNA based cytology, and cyst fluid analysis for potential molecular markers needs further investigation.