Needle-based Confocal Laser Endomicroscopy Research Articles

In vivo real-time diagnosis of endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in gastric subepithelial lesions.

The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. Consecutive patients with gastric SELs ≥1cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month washout period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P>0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1=poor and 5=excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma, and carcinoma. Endoscopic ultrasound-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

Endoscopic ultrasonography for the evaluation of pancreatic cystic neoplasms.

Endoscopic ultrasonography (EUS) is a modality with high spatial resolution that enables comprehensive observation of the entire pancreas and plays an important role in the diagnosis of pancreatic lesions. Recent advances in diagnostic imaging methods such as ultrasound, computed tomography, and magnetic resonance imaging have increased the incidental detection of pancreatic cystic lesions (PCLs). EUS has been recognized as an essential diagnostic method for the detection and evaluation of PCLs. EUS has two important roles: as a detailed (high-resolution) imaging diagnostic method and as an approach for collecting cyst fluid content by EUS-guided fine needle aspiration for pathological diagnosis or biomarker evaluation. Furthermore, in recent years, the usefulness of contrast-enhanced EUS for the differential diagnosis of PCLs or evaluation of grade of malignancy, and a novel imaging technique called needle-based confocal laser endomicroscopy to observe intraductal structures through a needle, has been reported. An understanding of the morphological characteristics of PCLs depicted by ultrasound imaging and of the benefits and limitations of EUS diagnosis in daily practice is needed.

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.).

Pancreatic Cysts: Diagnostic Role of EUS-Guided Microforceps Biopsy and Confocal Laser Endomicroscopy.

Frequent use of high-quality cross-sectional imaging has led to a significant rise in diagnosis of pancreatic cystic lesions (PCLs). Despite the fact that enormous effort has been put into the research of PCLs within the last two decades and multiple guidelines have been developed, our clinical decision-making especially in regard to mucinous lesions remains limited. Currently, clinical assessment, cross-sectional imaging and EUS with fluid analysis (if appropriate) belong to the standard care in patients with PCLs. For differentiation of mucinous from nonmucinous cysts, the sensitivity of cytological investigation and CEA in the cyst fluid is 42% and 52-79%, respectively. Due to the limited accuracy, further diagnostic tools are warranted. Two EUS-guided approaches have been introduced recently. Through-the-(19-gauge EUS) needle Moray microforceps have been developed, and several studies have acknowledged their contribution to the correct diagnosis as they help to overcome limited cellularity of the EUS-guided cyst fluid aspiration and traditional cytology. Confocal laser endomicroscopy offers real-time images and seems to be a promising method for the diagnosis and differential diagnosis of pancreatic PCLs. Example images of the needle-based confocal laser endomicroscopy criteria for the diagnosis of PCLs have been suggested recently. Before both, Moray microforceps and confocal laser endomicroscopy can be widely accepted, further studies are necessary to determine the real diagnostic yield and the clinical efficacy.

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.

A prospective trial of CONfocal endomicroscopy in CYSTic lesions of the pancreas: CONCYST-01.

Background and study aims Pancreatic cystic lesions (PCL) are common. While some harbor malignant potential, accurate preoperative diagnosis remains challenging. Needle-based confocal laser endomicroscopy (nCLE) via a 19G FNA needle enables real-time imaging of the cyst wall. This study evaluated the safety and utility of nCLE in patients with an indeterminate PCL undergoing EUS-FNA. Patients and methods The CONCYST study prospectively recruited patients with indeterminate PCL attending three hepatopancreaticobiliary (HPB) referral centers in the UK, with indeterminate PCL, who required EUS-FNA between July 2014 and October 2016. Following the procedure, all patients were followed up in telephone clinic for at least 12 months. Ethical approval for the study was granted by the National Research Ethics Service (14/LO/0040). Results Sixty-seven patient were recruited, 11 excluded and 56 included in the final analysis: 35 male, 21 female; median age 68 (range 28 – 80). Recognizable confocal images were obtained in 48 of 56 cases. Median nCLE scanning time was 5 minutes and did not exceed 10 minutes in any case. EUS-nCLE findings correlated with final diagnosis (based on imaging, cytology and multidisciplinary team review) in 43/56 (77 %) of cases, compared with 37/56 (66 %) for cytology alone ( P = 0.12). One patient experienced mild pruritus following the procedure and another developed an infected pseudocyst, which resolved with antibiotics. Conclusions EUS-nCLE under conscious sedation in the day case setting is safe and provides additional information to standard EUS-FNA for diagnosing indeterminate PCL.

Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions

Background and aimThe diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs.MethodsRetrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case.ResultsThe addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33–0.49) to 0.64 (CI 95% 0.61–0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76).ConclusionThe addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.

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.

Endoscopic Ultrasound-guided Needle-based Confocal Laser Endomicroscopy: Appraisal Concerning In-vivo Imaging of Intraductal Papillary Mucinous Neoplasm

Differential diagnosis between benign and potentially malignant cystic pancreatic lesions may be difficult. Previously we have compared cyst fluid serine protease inhibitor Kazal type I (SPINK1) with some traditionally used tumour markers (amylase, CEA, Ca19-9) and found that it may be a new promising maker in the differential diagnosis of cystic pancreatic lesions. In the present study, we focused on cyst fluid SPINK1 levels in benign and potentially malignant cystic pancreatic lesions.Sixty-one patients operated on for cystic pancreatic lesion in Tampere University Hospital, Finland and in Verona University Hospital, Italy, were included. Cyst fluid was aspirated during surgery, stored at −70 °C, and analysed with immunofluorometric assay for SPINK1. The final diagnosis was acute pancreatitis with fluid collection (Acute FC) in 4 patients, chronic pseudocyst (PS) in 17 patients, serous cystadenoma (SCA) in 7 patients, mucinous cystadenoma (MCA) in 21 patients and intraductal papillary-mucinous neoplasm (IPMN) in 12 patients (9 main/mixed duct type and 3 branch duct type).The acute FC patients had high SPINK1 levels. Among chronic cysts, SPINK1 levels were significantly higher in patients with potentially malignant cysts (main/mixed duct IPMN and MCA) than with benign cysts (side branch IPMN and SCA), (median and range, [480 (13–3602) vs. 18 (0.1–278) μg/L]; p < 0.0001). In the subcohort of 24 patients with <3 cm chronic cyst, cyst fluid SPINK 1 levels were significantly lower in SCA or side branch IPMN (3 [2–116] μg/L) than in main duct IPMN or MCA (638 [66–3602] μg/L; p = 0.018). The best sensitivity and specificity to differentiate any size MCA or main/mixed type IPMN from SCA or side branch IPMN were 85% and 84% (AUC 0.94; cut-off value 118 μg/L). The best sensitivity and specificity to differentiate <3 cm MCA or main duct IPMN from SCA or side branch IPMN were 93% and 89% (AUC 0.98; cut-off value 146 μg/L).Cyst fluid SPINK1 may be a possible marker in the differential diagnosis of benign and potentially malignant cystic pancreatic lesions.

Video Comment on Ming-Ming Zhang et al.

Ming-Ming Zhang et al. Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of gastric subepithelial tumors: a pilot study

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

Needle-based confocal laser endomicroscopy for real-time diagnosingand staging of lung cancer.

Diagnosing lung cancer in the absence of endobronchial abnormalities is challenging. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging of cells. We assessed the feasibility and safety of using nCLE for real-time identification of lung cancer.In patients with suspected or proven lung cancer scheduled for endoscopic ultrasound (EUS), lung tumours and mediastinal lymph nodes were imaged with nCLE before fine-needle aspiration (FNA) was performed. nCLE lung cancer characteristics were identified by comparison with pathology. Multiple blinded raters validated CLE videos of lung tumours and mediastinal nodes twice.EUS-nCLE-FNA was performed in 22patients with suspected or proven lung cancer in whom 27lesions (six tumours, 21 mediastinal nodes) were evaluated without complications. Three nCLE lung cancer criteria (dark enlarged pleomorphic cells, dark clumps and directional streaming) were identified. The accuracy of nCLE imaging for detecting malignancy was 90% in tumours and 89% in metastatic lymph nodes. Both inter-observer agreement (mean κ=0.68, 95% CI 0.66-0.70) and intra-observer agreement (mean±sd κ=0.70±0.15) were substantial.Real-time lung cancer detection by endosonography-guided nCLE was feasible and safe. Lung cancer characteristics were accurately recognised.

Diagnosis of Pancreatic Cystic Lesions by Virtual Slicing: Comparison of Diagnostic Potential of Needle-Based Confocal Laser Endomicroscopy versus Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Background: Pancreatic cystic lesions are often challenging entities for diagnosis and management. EUS-FNA diagnostic accuracy is limited by paucicellularity of cytology specimens and sampling errors. Needle-based confocal laser endomicroscopy (nCLE) provides real-time imaging of the microscopic structure of the cystic lesion and could result in a more accurate diagnosis. Aims and Objectives: To determine the diagnostic utility of in vivo nCLE and EUS-FNA in the diagnosis and histologic characterization of pancreatic cystic lesions (PCL). Materials and Methods: All patients diagnosed with PCL who had undergone nCLE and FNA over a 10-year period within a major urban teaching hospital were included in this study. All gastroenterology reports of the nCLE images and corresponding pathologist findings from the EUS-FNA were collected and compared with, a final diagnosis prospectively collected from clinicopathological and imaging data. Results: A total of n=32 patients were included in this study, which consisted of n=13 serous cystadenoma (SCA), n=7 intraductal papillary mucinous neoplasms (IPMN), n=2 mucinous cystic neoplasms (MCN), n=3 well-differentiated neuroendocrine tumors, n=2 cysts, n=2 benign pancreatic lesions, n=1 adenocarcinoma, n=1 gastrointestinal stromal tumor (GIST) and n=1 lymphangioma. The overall diagnostic rate was higher in nCLE (87.5%) vs. EUS-FNA (71.9%) While the diagnostic accuracy of nCLE and EUS-FNA were comparable in characterization of benign vs. malignant lesions, the nCLE diagnosis demonstrated higher accuracy rate in identifying mucinous cystic neoplasms compared to EUS-FNA. Conclusion: nCLE is a useful companion diagnostic tool for pancreatic cystic lesions and could assist the cytopathologist to better triage the sample for required ancillary testing and treatment planning. The combination of nCLE and EUS-FNA may be especially helpful in reducing the proportion of cases categorized as non-diagnostic.

Current indications and yield of endoscopic ultrasound and ancillary techniques in pancreatic cystic neoplasms

An increase in the diagnosis of pancreatic cystic neoplasm has been described lately. Surgical treatment or surveillance is advised depending on the type of lesion diagnosed. The most accurate diagnostic approach is needed to make the best therapeutic decision. Endoscopic ultrasound is a very valuable tool in the evaluation of pancreatic cystic neoplasm. It generates high-quality images and allows the possibility of sampling the cystic fluid for cytology, microbiological and molecular evaluation. Even with this evaluation, the sensitivity of this approach is not always adequate. New technological resources have been developed to try to improve the diagnostic accuracy of pancreatic cystic neoplasms. The two most promising techniques are needle-based confocal laser endomicroscopy and contrast-enhanced harmonic endoscopic ultrasound. Needle-based confocal laser endomicroscopy allows a microscopic evaluation of mucosal glands and vascular pattern, to differentiate mucinous from non-mucinous lesions. Contrast-enhanced harmonic endoscopic ultrasound is used for the vascular evaluation of the microcirculation of the cyst wall and mural nodule, mainly to make the difference between malignant nodules and mucus plugs. A combination of these different diagnostic techniques can improve the diagnostic accuracy of pancreatic cystic neoplasms to offer the adequate therapeutic decision.

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.

Endoscopic diagnosis of cystic lesions of the pancreas

Endoscopic methods are increasingly used in the diagnosis of cystic lesions of the pancreas. The two major endoscopic approaches are endoscopic ultrasonography (EUS) and transpapillary diagnosis. EUS-guided fine-needle aspiration cytology and EUS-guided fine needle-based confocal laser endomicroscopy have been used in the differential diagnosis of mucinous and non-mucinous pancreatic cysts. EUS is the most sensitive modality for detecting mural nodules (MN) in intraductal papillary mucinous neoplasms (IPMN). Contrast-enhanced harmonic EUS (CH-EUS), as an add-on to EUS, is useful for identifying and characterizing MN. Recent studies show that CH-EUS has a sensitivity of 60-100% and a specificity of 75-92.9% for diagnosing malignant cysts. Intraductal ultrasonography and peroral pancreatoscopy are especially useful for detecting MN and IPMN. A recent meta-analysis showed that cytological assessment of pancreatic juice using a transpapillary approach had a pooled sensitivity, specificity, and accuracy of 35.1%, 97.2%, and 92.9%, respectively, for diagnosing malignant IPMN. Further studies are warranted to determine the indications for each of these novel techniques in assessing cystic lesions of the pancreas.

Confocal Laser Endomicroscopy and Optical Coherence Tomography for the Diagnosis of Prostate Cancer: A Needle-Based, In Vivo Feasibility Study Protocol (IDEAL Phase 2A).

BackgroundFocal therapy for prostate cancer has been proposed as an alternative treatment to whole-gland therapies in selected men to diminish side effects in localized prostate cancer. As nowadays imaging cannot offer complete prostate cancer disease characterization, multicore systematic biopsies are recommended (transrectal or transperineal). Optical imaging techniques such as confocal laser endomicroscopy and optical coherence tomography allow in vivo, high-resolution imaging. Moreover, they can provide real-time visualization and analysis of tissue and have the potential to offer additive diagnostic information.ObjectiveThis study has 2 separate primary objectives. The first is to assess the technical feasibility and safety of in vivo focal imaging with confocal laser endomicroscopy and optical coherence tomography. The second is to identify and define characteristics of prostate cancer and normal prostate tissue in confocal laser endomicroscopy and optical coherence tomography imaging by comparing these images with the corresponding histopathology.MethodsIn this prospective, in vivo feasibility study, needle-based confocal laser endomicroscopy and optical coherence tomography imaging will be performed before transperineal template mapping biopsy or radical prostatectomy. First, confocal laser endomicroscopy and optical coherence tomography will be performed in 4 patients (2 for each imaging modality) undergoing transperineal template mapping biopsy to assess the feasibility and safety of confocal laser endomicroscopy and optical coherence tomography. If proven to be safe and feasible, confocal laser endomicroscopy and optical coherence tomography will be performed in 10 patients (5 for each imaging modality) undergoing radical prostatectomy. Confocal laser endomicroscopy and optical coherence tomography images will be analyzed by independent, blinded observers. Confocal laser endomicroscopy– and optical coherence tomography–based qualitative and quantitative characteristics and histopathology will be compared. The study complies with the IDEAL (Idea, Development, Exploration, Assessment, Long-term study) stage 2a recommendations.ResultsAt present, the study is enrolling patients and results and outcomes are expected in 2019.ConclusionsConfocal laser endomicroscopy and optical coherence tomography are promising optical imaging techniques that can visualize and analyze tissue structure, possible tumor grade, and architecture in real time. They can potentially provide real-time, high-resolution microscopic imaging and tissue characteristics of prostate cancer in conjunction with magnetic resonance imaging or transrectal ultrasound fusion-guided biopsy procedures. This study will provide insight into the feasibility and tissue-specific characteristics of confocal laser endomicroscopy and optical coherence tomography for real-time optical analysis of prostate cancer.Trial RegistrationClinicalTrials.gov NCT03253458; https://clinicaltrials.gov/ct2/show/NCT03253458 (Archived by WebCite at http://www.webcitation.org/6z9owM66B)Registered Report IdentifierRR1-10.2196/9813

Su1341 - Cost Analysis of Upfront Needle-Based Confocal Laser Endomicroscopy for Pancreatic Cystic Lesions via Current Aga and Fukuoka Guidelines

Su1341 - Cost Analysis of Upfront Needle-Based Confocal Laser Endomicroscopy for Pancreatic Cystic Lesions via Current Aga and Fukuoka Guidelines