EUS-guided Needle-based Confocal Laser Endomicroscopy Research Articles

Endoscopic Ultrasound-Guided Needle-Based Confocal Endomicroscopy as a Diagnostic Imaging Biomarker for Intraductal Papillary Mucinous Neoplasms.

Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2030, yet there is a lack of accurate diagnostic tests for early detection. Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer and are increasingly being detected. Despite the development and refinement of multiple guidelines, diagnosing high-grade dysplasia or cancer in IPMNs using clinical, radiologic, endosonographic, and cyst fluid features still falls short in terms of accuracy, leading to both under- and overtreatment. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel technology that allows real-time optical biopsies of pancreatic cystic lesions. Emerging data has demonstrated that EUS-nCLE can diagnose and risk stratify IPMNs more accurately than conventional diagnostic tools. Implementing EUS-nCLE in clinical practice can potentially improve early diagnosis of pancreatic cancer, reduce unnecessary surgeries of IPMNs with low-grade dysplasia, and advance the field of digital pathomics. In this review, we summarize the current evidence that supports using EUS-nCLE as a diagnostic imaging biomarker for diagnosing IPMNs and for risk stratifying their degree of neoplasia. Moreover, we will present emerging data on the role of adding artificial intelligence (AI) algorithms to nCLE and integrating novel fluid biomarkers into nCLE.

Role of Endoscopic Ultrasound in the Evaluation of Pancreatic Cystic Neoplasms: A Concise Review.

Pancreatic cystic lesions are being discovered as incidental lesions during cross-sectional imaging studies of the abdomen with increasing frequency. Endoscopic ultrasound is an important diagnostic modality for managing pancreatic cystic lesions. There are various types of pancreatic cystic lesions, from benign to malignant. Endoscopic ultrasound has a multifactorial role in delineating the morphology of pancreatic cystic lesions, ranging from fluid and tissue acquisition for analysis-fine needle aspiration and through-the-needle biopsy, respectively-to advanced imaging techniques, such as contrast-harmonic mode endoscopic ultrasound and EUS-guided needle-based confocal laser endomicroscopy. In this review, we will summarize and provide an update on the specific role of EUS in the management of pancreatic cystic lesions.

Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions: A Network Meta-Analysis.

Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.

Efficacy of EUS-guided needle-based confocal laser endomicroscopy in the diagnosis of pancreatic lesions: A systematic review and meta-analysis.

Needle-based confocal laser endomicroscopy (nCLE) is a procedure in which an AQ-Flex nCLE mini-probe is passed through an EUS-FNA needle into a pancreatic lesion to enable subsurface in vivo tissue analysis. In this study, we conducted a systematic review and meta-analysis of nCLE for the diagnosis of pancreatic lesions. We conducted a comprehensive search of several databases and conference proceedings, including PubMed, EMBASE, Google-Scholar, MEDLINE, SCOPUS, and Web of Science databases (earliest inception to March 2020). The primary outcomes assessed the pooled rate of diagnostic accuracy for nCLE and the secondary outcomes assessed the pooled rate of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and adverse events (AE) of nCLE to diagnose premalignant/malignant pancreatic lesions. Eleven studies on 443 patients were included in our analysis. The pooled rate of diagnostic accuracy of EUS nCLE was 83% (95 confidence interval [CI] = 79-87; I 2 = 0). The pooled rate of sensitivity, specificity, PPV and NPV of EUS nCLE was 85.29% (95% CI = 76.9-93.68; I 2 = 85%), 90.49% (95% CI = 82.24-98.74; I 2 = 64%), 94.15% (95% CI = 88.55-99.76; I 2 = 68%), and 73.44% (95% CI = 60.16-86.72; I 2 = 93%), respectively. The total AE rate was 5.41% (±5.92) with postprocedure pancreatitis being the most common AE at 2.28% (±3.73). In summary, this study highlights the rate of diagnostic accuracy, sensitivity, specificity, and PPV for distinguishing premalignant/malignant lesions. Pancreatic lesions need to be further defined with more validation studies to characterize CLE diagnosis criteria and to evaluate its use as an adjunct to EUS-FNA.

High performance in risk stratification of intraductal papillary mucinous neoplasms by confocal laser endomicroscopy image analysis with convolutional neural networks (with video)

EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) can differentiate high-grade dysplasia/adenocarcinoma (HGD-Ca) in intraductal papillary mucinous neoplasms (IPMNs) but requires manual interpretation. We sought to derive predictive computer-aided diagnosis (CAD) and artificial intelligence (AI) algorithms to facilitate accurate diagnosis and risk stratification of IPMNs. A post hoc analysis of a single-center prospective study evaluating EUS-nCLE (2015-2019; INDEX study) was conducted using 15,027 video frames from 35 consecutive patients with histopathologically proven IPMNs (18 with HGD-Ca). We designed 2 CAD-convolutional neural network (CNN) algorithms: (1) a guided segmentation-based model (SBM), where the CNN-AI system was trained to detect and measure papillary epithelial thickness and darkness (indicative of cellular and nuclear stratification), and (2) a reasonably agnostic holistic-based model (HBM) where the CNN-AI system automatically extracted nCLE features for risk stratification. For the detection of HGD-Ca in IPMNs, the diagnostic performance of the CNN-CAD algorithms was compared with that of the American Gastroenterological Association (AGA) and revised Fukuoka guidelines. Compared with the guidelines, both n-CLE-guided CNN-CAD algorithms yielded higher sensitivity (HBM, 83.3%; SBM, 83.3%; AGA, 55.6%; Fukuoka, 55.6%) and accuracy (SBM, 82.9%; HBM, 85.7%; AGA, 68.6%; Fukuoka, 74.3%) for diagnosing HGD-Ca, with comparable specificity (SBM, 82.4%; HBM, 88.2%; AGA, 82.4%; Fukuoka, 94.1%). Both CNN-CAD algorithms, the guided (SBM) and agnostic (HBM) models, were comparable in risk stratifying IPMNs. EUS-nCLE-based CNN-CAD algorithms can accurately risk stratify IPMNs. Future multicenter validation studies and AI model improvements could enhance the accuracy and fully automatize the process for real-time interpretation.

Confocal endomicroscopy for evaluation of pancreatic cystic lesions: a systematic review and international Delphi consensus report.

Background and study aims The aim of thi systematic review and consensus report is to standardize the practice of endoscopic ultrasound (EUS-guided needle-based confocal laser endomicroscopy (nCLE) for pancreatic cystic lesion (PCL) evaluation. Methods We performed an international, systematic, evidence-based review of the applications, outcomes, procedural processes, indications, training, and credentialing of EUS-nCLE in management of PCLs. Based on available clinical evidence, preliminary nCLE consensus statements (nCLE-CS) were developed by an international panel of 15 experts in pancreatic diseases. These statements were then voted and edited by using a modified Delphi approach. An a priori threshold of 80 % agreement was used to establish consensus for each statement. Results Sixteen nCLE-CS were discussed. Thirteen (81 %) nCLE-CS reached consensus addressing indications (non-communication PCL meeting criteria for EUS-FNA or with prior non-diagnostic EUS-FNA), diagnostic outcomes (improved accuracy for mucinous PCLs and serous cystadenomas with substantial interobserver agreement of image patterns), low incidence of adverse events (fluorescein-associated and pancreatitis), procedural processes (nCLE duration, manipulation of needle with probe), and training (physician knowledge and competence). Conclusion Based on a high level of agreement pertaining to expert consensus statements, this report standardizes the practice of EUS-nCLE. EUS-nCLE should be systematically considered when EUS-FNA is indicated for PCL evaluation.

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 )

Appraisal of EUS-guided needle-based confocal laser endomicroscopy in the diagnosis of pancreatic lesions: A single Chinese center experience.

Background and Objectives:In the recent years, EUS is one of the routine procedures in the diagnosis of pancreatic diseases. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel minimally invasive imaging technique in diagnosis of pancreatic diseases. The pilot researches provided us some preliminary findings and conclusions with small samples, low rate of pathological correspondence. The aim of this current study was to evaluate the diagnostic efficacy of EUS-guided nCLE in solid pancreatic lesions (SPLs) and pancreatic cystic lesions (PCLs) based on large samples. The date was obtained on nCLE imaging findings and high rate of correlation with pathology.Material and Methods:Patients enrolled in the study were underwent EUS-nCLE to achieve the nCLE images and diagnosis. Comparing with the final diagnosis, including surgical histopathological results or cyto-/histopathology through FNA, the efficacy and accuracy of nCLE in diagnosis in solid and cystic pancreatic lesions were evaluated. In other cases, clinical diagnoses were achieved based on the combination with clinical history, image findings and fluid analysis and cytology, by 3 independent committee members strongly agreed with a concordant diagnosis.Results:Totally 172 patients were enrolled into the study. The overall rate of final diagnosis was about 65% while 50% in cystic lesion. The mean sensitivity, specificity, negative predictive value, positive predictive value and accuracy of the nCLE in diagnosis of PDAC is 90.3%, 89.5%, 93.3%, 85.0% and 90.0% respectively. The efficacy and accuracy of pancreatic cystic lesions were very satisfying and some additional nCLE signs were found, including “black aggregates of cells, forming as gland-like structure, surrounding by fibro and vessels” in neuroendocrine tumors (NETs); “black columnar protrusions near vascular area” in the pseudopapillary solid tumor (SPT); macrophage in tuberculosis (TB) and small aggregate of black regular cells maybe corresponds to ovarian-like stroma in mucinous cystadenoma (MCN). In the study, 20 (11.6%) patients suffered complications, including symptomatic (5.2%) and asymptomatic (6.4%).Conclusions:nCLE observation could improve characterization of indeterminate cysts, or confirm the EUS impression, when cytological confirmation is missing. The technique may deliver information to better guide our clinical decisions.

33 Needle-Base Confocal Laser Endomicroscopy in the Diagnosis of Pancreas Cyst: A Systematic Review and Meta-Analysis

INTRODUCTION: EUS-guided needle-based confocal laser endomicroscopy (nCLE) provides real-time histology assessments and has been reported as an adjunctive tool that can be performed in the same session as EUS-fine needle aspiration. We aimed to perform a systematic review and meta-analysis regarding the diagnostic performance, success rate, and complications of nCLE in pancreas cysts. METHODS: This is a systematic review and meta-analysis following the PRISMA-P principles. Literature was systematically searched in February 2019 by two independent investigators in 3 major databases including PubMed, Embase, and Web of Science by using the terms “confocal endomicroscopy” AND “needle” AND “pancreas cyst.” The search was limited to English-written and in vivo human studies. Additionally, investigators manually reviewed the references of the primary identified studies for other eligible articles. The meta-analysis of success rate, complication rate, pooled diagnostic parameters with the respective 95% confidence interval (CI) of nCLE for diagnosis of pancreas cysts were performed. RESULTS: Of the 159 initially screened studies, 11 studies had 288 patients with pancreatic cystic lesions enrolled. The estimated overall success rate and adverse event rate with random effects model were 96% (95% CI: 92–95%) and 11% (95% CI: 7.5–16%), respectively. There were 7 studies which included 176 patients that reported the diagnostic parameters of nCLE for diagnosis of mucinous pancreas cyst. The estimated diagnostic odd ratio (DOR) was 50 (95% CI: 18.92–132.16). The estimated area under curve (AUC) was 0.939 (95% CI: 0.89–0.992) and AUC for SROC was 0.84 (95% CI: 0.72–0.98). The estimate sensitivity and specificity were 0.77 (95% CI: 0.62–0.87) and 0.91 (95% CI: 0.81–0.96), respectively. The meta-analysis estimated the prevalence rate of mucinous cysts to be 57% (95% CI: 43%–71%). The positive predictive value (PPV) and negative predictive value (NPV) were 0.91 (range: 0.86–0.95) and 0.72 (range: 0.62, 0.84), respectively. I2 index showed no heterogeneity between studies in success rate, adverse event rate, DOR, and specificity. However, heterogeneity was detected in sensitivity, PPV, and NPV between studies. CONCLUSION: nCLE has high sensitivity, specificity, PPV, and NPV for differentiating mucinous pancreas cyst from the other cystic lesion. However there is an increased adverse rate compared to standard EUS-FNA. Measures and methods to decrease the adverse event rate should be further investigated.

EUS-guided confocal laser endomicroscopy: prediction of dysplasia in intraductal papillary mucinous neoplasms (with video)

Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial "width" and "darkness" were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ= 0.61; 95% CI, 0.51-0.71) and moderate (κ= 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.).

Endoscopic diagnosis of pancreatic cysts.

Pancreatic cystic lesions (PCLs) are increasingly identified on abdominal imaging. Given the malignant potential of certain cyst subtypes and the poor survival rates of pancreatic cancer, accurate diagnosis and appropriate management of these cysts are critical. Advances in endoscopic ultrasound (EUS)-guided diagnostics have increased the accuracy of differentiating PCLs. These include cyst fluid molecular analysis, EUS-guided needle-based confocal laser endomicroscopy, and EUS-guided through the needle microforceps biopsy. This review encapsulates recent advances in the endoscopic management of PCLs with a specific focus on EUS-guided diagnosis. It is important to accurately diagnose pancreatic cystic lesions with malignant potential where the definitive management is surgical resection. Misdiagnosis can result in inadvertent surgery of an otherwise benign lesion or malignant progression of a precancerous cyst. Moreover, pancreatic surgery is associated with significant morbidity and mortality. Recent advances in EUS-guided tissue acquisition, imaging, and molecular biomarkers have resulted in improved diagnostic accuracy of pancreatic cystic lesions. Future studies need to define efficient and accurate diagnostic algorithms for improved management of pancreatic cysts.

589 – Qualitative Derivation and Quantitative Prediction of Dyplasia in Intraductal Papillary Mucinous Neoplasms Using Eus-Guided Needle-Based Confocal Laser Endomicroscopy

589 – Qualitative Derivation and Quantitative Prediction of Dyplasia in Intraductal Papillary Mucinous Neoplasms Using Eus-Guided Needle-Based Confocal Laser Endomicroscopy

Mo2052 – Application of Machine Learning and Artificial Intelligence in the Detection of Dyplasia in Intraductal Papillary Mucinous Neoplasms Using Eus-Guided Needle-Based Confocal Laser Endomicroscopy

Mo2052 – Application of Machine Learning and Artificial Intelligence in the Detection of Dyplasia in Intraductal Papillary Mucinous Neoplasms Using Eus-Guided Needle-Based Confocal Laser Endomicroscopy

An International External Interobserver and Derivation Study for the Detection of Advanced Neoplasia in IPMNs Using Confocal Laser Endomicroscopy

Introduction: Prior studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of IPMNs by detection of characteristic “papillae”. We sought to further assess the performance and interobserver agreement (IOA) of EUS-nCLE for differentiating IPMNs with high grade dysplasia (HGD) or adenocarcinoma (HGD-Ca) from those with low or intermediate-grade dysplasia (LGD). Methods: In a prospective single center study evaluating EUS-nCLE for the evaluation of pancreatic cysts, 26 patients with a definitive diagnosis of IPMNs (surgery=24; confirmatory cytology/metastatic adenocarcinoma=2) were identified. EUS-nCLE imaging variables predictive (Table 1) of advanced neoplasia were internally derived amongst 3 EUS-MDs with experience in nCLE (Fig. 1). Six external endosonographers (nCLE experience>30 cases) blinded to all clinical data, reviewed all nCLE videos (Fig. 2).5_A Figure 1. EUS-guided needle based confocal endomicroscopy imaging features in differentiating degree of dysplasia in IPMNs5_B Figure 2. EUS-guided needle based confocal endomicroscopy imaging variables predictive of advanced neoplasia: diagnostic parameters and interobserver agreement. CI: Confidence Interval.After 2 weeks, the assessors reviewed the same images in a different sequence. A self-study tutorial of nCLE variables predictive of HGD-Ca was provided before each review. Prior to the second review, an interactive web-based discussion was also conducted. The IOAs (κ statistic) of diagnostic nCLE image patterns to detect HGD-Ca were calculated.5_C Figure 3. Study designResults: Among the subjects with IPMNs (16 mixed, 10 branch-duct; mean size 3.4±1.7 cm), there were 9 with LGD and 17 with advanced neoplasia (12 HGD, 2 non-invasive and 3 invasive adenocarcinoma). The six observers identified papillary structures diagnostic of IPMN in all videos. The overall sensitivity, specificity, accuracy, and IOA of EUS-nCLE to diagnose HGD-Ca was 90%, 73%, 84%, and κ=0.54 (moderate), respectively (Table 1). Correlating with histopathological progression of dysplasia in IPMNs, nCLE imaging characteristics of papillary “thickness” (indicative of cellular and nuclear stratification) and “darkness” (increased nuclear/cytoplasmic ratio) were the most sensitive (90% and 91%) and accurate (86% and 84%) with substantial (κ=0.61) and moderate (κ=0.55) IOAs for detecting HGD-Ca, respectively (Table 1). Conclusion: In this derivation study, blinded expert endosonographers identified several EUS-nCLE imaging features of IPMNs that are associated with advanced neoplasia. Further studies are needed to refine and validate these features for applying EUS-nCLE to identify advanced dysplasia.

A Young Man With a Mucinous Cystic Neoplasm of the Pancreas: EUS-nCLE to the Rescue

Pancreatic cystic lesions (PCLs) are becoming more readily identified with advances in imaging technology; however, distinguishing which cysts harbor the potential for malignancy continues to remain a clinical challenge. Identifying premalignant mucinous PCLs including mucinous cystic neoplasms (MCNs) may guide early surgical intervention versus endoscopic surveillance. Novel diagnostic modalities such as EUS-guided needle based confocal laser endomicroscopy (EUS-nCLE) provide real-time in vivo imaging of PCL epithelium and may aide in diagnosing mucinous PCLs. While MCNs are particularly frequent (90%-98%) in women, we present an unusual case of pancreatic MCN in a young man who was diagnosed by EUS-nCLE when current standard of care failed to reveal the diagnosis. A 38-year-old man with well-controlled ulcerative colitis presented with persistent right lower quadrant pain. Imaging with MRI enterography to evaluate for possible small bowel disease incidentally revealed a 5.9 cm pancreatic tail cyst. Patient denied prior history of smoking, alcohol use, gallstone disease or acute pancreatitis. He underwent an EUS which revealed a 5x6 cm anechoic cystic tail lesion with a thick wall. Fine needle aspiration indicated fluid CEA of 9.9ng/ml, amylase of 65,800 U/L and no malignant cells or mucin on cytology. Furthermore, molecular analysis of the cyst fluid by next generation sequencing did not reveal any known mutations. EUS-nCLE was performed and real-time image acquisition revealed multiple solitary epithelial bands in a horizon configuration with variable thickness, consistent with MCN features (Figure 1). The patient underwent a distal pancreatectomy and splenectomy with final pathology revealing MCN with low grade dysplasia (Figure 2). The postoperative course was uncomplicated and in follow up visits patient reported resolution of abdominal pain. Here we show a case where current standard of care (CEA and cytology) failed to identify a MCN lesion. The differentiation of PCLs continues to remain challenging and novel technology including nCLE may improve diagnostic accuracy of mucinous PCLs. Of note, the nCLE description of epithelial bands in horizon configuration have been reproduced in both in vivo and ex vivo CLE imaging with histopathological correlation. Moreover, this case is further unique in that MCNs are only present in 2-10% of men. This report further adds to the current literature on CLE supplementation in the management of PCLs.Figure: MCN with Gross HE 40x. The corresponding histologic section shows that the cyst is lined by columnar cells overlying ovarian type-stroma. The atypia seen in the columnar cells is classified as low-grade dysplasia.Figure: EUS-nCLE demonstrated epithelial bands (black arrows) which are characteristic of mucinous cystic neoplasms. These can be either solitary or appear in layers. (Resolution 20 microns).

EUS-guided needle-based confocal laser endomicroscopy (nCLE) findings in cystic lesions of the pancreas (CLP)

EUS-guided needle-based confocal laser endomicroscopy (nCLE) findings in cystic lesions of the pancreas (CLP)

Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos)

EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n= 23) or clinical (n= 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ= 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ= 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ= 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ= 0.85 ± 0.11 (almost perfect), respectively. EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).

A Primary Keratinizing Squamous Cell Carcinoma of the Pancreas: Endosonography and Confocal Endomicroscopy of an Unusual Pancreatic Cystic Lesion

Case Report: A 79-year-old woman presented with abdominal discomfort and unintentional weight loss. A computed tomography scan demonstrated a 7 cm complex pancreatic cystic lesion (PCL) along with multiple hepatic cystic lesions. Endoscopic ultrasound (EUS) demonstrated a 7.1 x 6.7 cm anechoic cystic lesion with an irregularly thick wall and multiple mural nodules in the pancreatic body without obvious communication with the main pancreatic duct. On protocol, EUS-guided needle-based confocal laser endomicroscopy (nCLE) with an AQ-Flex 19 miniprobe (Cellvizio, Mauna Kea Technologies, Paris, France) revealed large cells of unequal shapes and sizes (> 20 μ) suggestive of a malignant process. Fine needle aspiration (FNA) confirmed a diagnosis of pancreatic keratinizing squamous cell carcinoma (SCC) metastatic to liver with demonstration of irregular spindle-like cells, hyperchromatic cells, and dense keratin material from both the primary pancreatic and metastatic liver lesions. Discussion: A primary pancreatic SCC constitutes a rare diagnosis with very few reports described in the literature. One large case series reviewed 5075 patients and reported the incidence of pure squamous cell carcinoma 0.5% of the total pancreatic ductal carcinomas1. Moreover, this case is unique for being an unusual presentation of a PCL where the diagnosis of malignancy was suspected by EUS-nCLE and confirmed with FNA. This adds to the growing literature of intracystic nCLE image patterns in the diagnosis of PCLs. 1) Baylor SM, Berg JW. Cross-classification and survival characteristics of 5,000 cases of cancer of the pancreas. J Surg Oncol 1973;5:335-358.

Su1328 EUS-Guided Needle-Based Confocal Laser Endomicroscopy in the Diagnosis of Cystic Pancreatic Neuroendocrine Tumor: Surgical Pathologic Correlation in Six Cases.

Su1328 EUS-Guided Needle-Based Confocal Laser Endomicroscopy in the Diagnosis of Cystic Pancreatic Neuroendocrine Tumor: Surgical Pathologic Correlation in Six Cases.