Needle-based Confocal Laser Endomicroscopy Research Articles

Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial)

IntroductionDespite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle...

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.

Endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions: a comprehensive review.

Advancements in diagnostic radiology have amplified the incorporation of these techniques into routine clinical practice. Concurrently, the frequency of incidentally identifying pancreatic cystic lesions (PCLs) has surged. PCLs encompass diverse categories contingent upon their origin. Among them, branch duct-intraductal papillary mucinous neoplasms (BD-IPMN) and mucinous cystic neoplasms (MCN) are categorized as mucinous cystic lesions that have malignant potential. Even solid neoplasms occasionally show cystic degeneration. Therefore, precise differential PCL diagnosis is crucial to optimize clinical management strategies and detect malignant transformations. Endoscopic ultrasound (EUS) affords comprehensive visualization of the pancreas with high-resolution ultrasound, complemented by fine-needle aspiration (FNA) under real-time EUS guidance, which is a minimally invasive procedure for obtaining pathological samples. This synergy has established EUS and EUS-FNA as vital procedures in the management of PCLs, enabling differentiation of PCLs. Cyst fluid analysis has played a pivotal role in deciding the optimal management strategy. The efficacy of cytological analysis is limited by scant cytologic material. The "string sign" test evaluates fluid viscosity, and its simplicity warrants initial consideration. Amylase and tumor markers, such as CEA, have been studied, but they yield varied sensitivity and specificity. Glucose and genetic mutations (KRAS, GNAS) exhibit promise, while comprehensive genomic profiling underscores genetic insights. Through-the-needle biopsy and needle-based confocal laser endomicroscopy also show high diagnostic yield. EUS-FNA, however, entails risks like infection and needle tract seeding, emphasizing the need for proper utilization. Pancreatic cyst fluid analysis augments diagnostic accuracy and informs clinical decisions, making it a valuable adjunct to imaging.

The role of needle-based confocal laser endomicroscopy in the diagnosis of pancreatic neuroendocrine tumors.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a highly accurate method for diagnosing pancreatic neuroendocrine tumors (PNETs); however, some PNETs are difficult to diagnose. Recently, the efficacy of needle-based confocal laser endomicroscopy (nCLE) in diagnosing solid pancreatic masses has been reported. However, the efficacy of nCLE in the diagnosis of PNETs remains unknown and only a small number of cases have been reported. Hence, this study aimed to evaluate the efficacy of nCLE in the diagnosis of PNETs. This single-center retrospective study evaluated 30 consecutive patients with suspected PNETs on contrast-enhanced computed tomography, who consented to nCLE combined with EUS-FNA and were diagnosed using EUS-FNA or surgical resection. The diagnostic criteria for PNETs using nCLE were based on the nesting and trabecular and glandular arrangement of tumor cell clusters surrounded by capillary vessels and fibrosis, as reported in previous studies. The diagnosis using nCLE was classified into three categories: misdiagnosis in three cases (10%), non-diagnostic in six cases (20%), and diagnostic in 21 cases (70%). nCLE was able to diagnose PNET in one of the two cases with inconclusive EUS-FNA. Although further development of the resolution and optimization of the diagnostic criteria are required, nCLE may constitute a useful diagnostic option in cases of inconclusive EUS-FNA for PNETs.

Needle-based confocal laser endomicroscopy for real-time granuloma detection.

Needle-based confocal laser endomicroscopy (nCLE) allows real-time microscopic imaging at the needle tip. nCLE malignancy criteria are used for tool-in-lesion confirmation during bronchoscopic lung nodule analysis. However, to date, nCLE criteria for granulomas are lacking. The aim was to identify and validate nCLE granuloma criteria and assess if blinded raters can distinguish malignant from granulomatous nCLE videos. In patients with suspected sarcoidosis, nCLE-imaging of mediastinal lymph nodes was performed during endoscopic ultrasound procedures, followed by needle aspiration. nCLE granuloma criteria were identified by comparison with pathology and final diagnoses. Additionally, nCLE-videos of granulomatous lung nodules part of prospective trials and clinical care were compared to the proposed nCLE granuloma criteria. Blinded raters validated nCLE videos of sarcoid and reactive mediastinal lymph nodes and malignant and granulomatous lung nodules twice. Granuloma criteria were identified (brighter-toned, homogeneous and well-demarcated lesions) based on nCLE-imaging in 14 sarcoidosis patients. Raters evaluated 26 nCLE-videos obtained in lymph nodes (n = 15 sarcoidosis; n = 11 reactive and total of 260 ratings). Granuloma criteria were recognized with 88% accuracy. The inter-observer (κ = 0.63, 95% CI 0.54-0.72) and intra-observer reliability (κ = 0.70 ± 0.06) were substantial. Based on 12 nCLE-videos obtained in lung nodules (n = 4 granulomas, n = 6 malignancy, n = 2 malignancy + granulomas and total of 120 ratings) granuloma and malignancy criteria were recognized with 92% and 75% accuracy. nCLE imaging facilitates real-time granuloma visualization. Blinded raters accurately and consistently recognized granulomas on nCLE-imaging and distinguished nCLE granuloma criteria from malignancy. Our data show the potential of nCLE as a real-time bronchoscopic guidance tool for lung nodule analysis.

Structured training program on confocal laser endomicroscopy for pancreatic cystic lesions: a multicenter prospective study among early-career endosonographers (with video)

Background and aimsThere are limited data about how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs). Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. MethodsTwenty-one early-career nCLE-naive endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at four weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous vs. non-mucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the gold standard. Learning curves were determined using cumulative sum analysis (CUSUM). ResultsAccuracy and diagnostic confidence for differentiating mucinous vs. non-mucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (p<0.001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial IOA (k=0.63). Accuracy for nCLE-guided PCL subtype diagnosis ranged from 82-96%. The learned nCLE skills did not deteriorate at eight weeks and were not impacted by a refresher session. ConclusionWe developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.

Needle-based confocal laser endomicroscopy for cystic lymphangiomas of the pancreas: the first case series.

Cystic lymphangiomas of the pancreas (CLP) were first described by Koch in 1913 [1]. The origin of these benign lesions is not well defined; they could either be congenital malformations or secondary to a lymphatic vessel obstruction due to either radiotherapy, surgery, infection, or trauma [2]. The main challenge in pancreatic cystic lesions (PCLs) is the diagnostic certainty [3]. Needle-based confocal laser endomicroscopy (nCLE), described in pancreatic diseases in 2011 [4], is a very specific technique for the diagnosis of the main PCL [5]. The first description of the identifiable structures by nCLE in CLP is proposed below.

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.

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.

Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules.

Robotic bronchoscopy has demonstrated high navigational success in small peripheral lung nodules but the diagnostic yield is discrepantly lower. Needle based confocal laser endomicroscopy (nCLE) enables real-time microscopic imaging at the needle tip. We aim to assess feasibility, safety and needle repositioning based on real-time nCLE-guidance during robotic bronchoscopy in small peripheral lung nodules. Patients with suspected peripheral lung cancer underwent fluoroscopy and radial EBUS assisted robotic bronchoscopy. After radial EBUS nodule identification, nCLE-imaging of the target area was performed. nCLE-malignancy and airway/lung parenchyma criteria were used to identify the optimal sampling location. In case airway was visualized, repositioning of the biopsy needle was performed. After nCLE tool-in-nodule confirmation, needle passes and biopsies were performed at the same location. Twenty patients were included (final diagnosis n= 17 (lung) cancer) with a median lung nodule size of 14.5 mm (range 8-28 mm). No complications occurred. In 19/20 patients, good quality nCLE-videos were obtained. In 9 patients (45%), real-time nCLE-imaging revealed inadequate positioning of the needle and repositioning was performed. After repositioning, nCLE-imaging provided tool-in-nodule-confirmation in 19/20 patients. Subsequent ROSE demonstrated representative material in 9/20 patients (45%) and overall diagnostic yield was 80% (16/20). Of the three patients with malignant nCLE-imaging but inadequate pathology, two were diagnosed with malignancy during follow-up. Robotic bronchoscopic nCLE-imaging is feasible and safe. nCLE-imaging in small, difficult-to-access lung nodules provided additional real-time feedback on the correct needle positioning with the potential to optimize the sampling location and diagnostic yield.

Endoscopic Ultrasound-Based Evaluation of Pancreatic Cysts: New Invasive Modalities

Pancreatic cysts are a heterogenous group of lesions that can be differentiated into mucinous and non-mucinous cysts based on their malignant potential. Crosssectional imaging alone is inadequate to reliably distinguish between the two groups. Endoscopic ultrasound (EUS) and fine needle aspiration has been used for analysis of the cyst morphology and cyst fluid. Traditional markers such as fluid carcinoembryonic antigen and cytology have been useful particularly for the assessment of indeterminate cysts or those with high-risk features, but the overall diagnostic accuracy is still sub-par. As a result, new techniques have been described to improve the ability of EUS to risk stratify a pancreatic cyst. In this review, we describe some of the novel EUS‑based techniques in the evaluation of pancreatic cysts, namely needle-based confocal laser endomicroscopy, through the needle cystoscopy, and through the needle biopsy techniques.

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.

Pancreatic Cystic Neoplasms.

Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".

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.

Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

Suspicious nodules detected by radiography are often investigated by biopsy, but the diagnostic yield of biopsies of small nodules is poor. Here we report a method—NIR-nCLE—to detect cancer at the cellular level in real-time during biopsy. This technology integrates a cancer-targeted near-infrared (NIR) tracer with a needle-based confocal laser endomicroscopy (nCLE) system modified to detect NIR signal. We develop and test NIR-nCLE in preclinical models of pulmonary nodule biopsy including human specimens. We find that the technology has the resolution to identify a single cancer cell among normal fibroblast cells when co-cultured at a ratio of 1:1000, and can detect cancer cells in human tumors less than 2 cm in diameter. The NIR-nCLE technology rapidly delivers images that permit accurate discrimination between tumor and normal tissue by non-experts. This proof-of-concept study analyzes pulmonary nodules as a test case, but the results may be generalizable to other malignancies.

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study.

BACKGROUNDCurrently, there is insufficient data about the accuracy in the diagnosing of pancreatic cystic lesions (PCLs), especially with novel endoscopic techniques such as with direct intracystic micro-forceps biopsy (mFB) and needle-based confocal laser-endomicroscopy (nCLE).AIMTo compare the accuracy of endoscopic ultrasound (EUS) and associated techniques for the detection of potentially malignant PCLs: EUS-guided fine needle aspiration (EUS-FNA), contrast-enhanced EUS (CE-EUS), EUS-guided fiberoptic probe cystoscopy (cystoscopy), mFB, and nCLE.METHODSThis was a single-center, retrospective study. We identified patients who had undergone EUS, with or without additional diagnostic techniques, and had been diagnosed with PCLs. We determined agreement among malignancy after 24-mo follow-up findings with detection of potentially malignant PCLs via the EUS-guided techniques and/or EUS-guided biopsy when available (EUS malignancy detection). RESULTSA total of 129 patients were included, with EUS performed alone in 47/129. In 82/129 patients, EUS procedures were performed with additional EUS-FNA (21/82), CE-EUS (20/82), cystoscopy (27/82), mFB (36/82), nCLE (44/82). Agreement between EUS malignancy detection and the 24-mo follow-up findings was higher when associated with additional diagnostic techniques than EUS alone [62/82 (75.6%) vs 8/47 (17%); OR 4.35, 95%CI: 2.70-7.37; P < 0.001]. The highest malignancy detection accuracy was reached when nCLE and direct intracystic mFB were both performed, with a sensitivity, specificity, positive predictive value, negative predictive value and observed agreement of 100%, 89.4%, 77.8%, 100% and 92.3%, respectively (P < 0.001 compared with EUS-alone). CONCLUSIONThe combined use of EUS-guided mFB and nCLE improves detection of potentially malignant PCLs compared with EUS-alone, EUS-FNA, CE-EUS or cystoscopy.

Image-guided in-Vivo Needle-Based Confocal Laser Endomicroscopy in the Prostate: Safety and Feasibility Study in 2 Patients.

Purpose: To assess the safety and technical feasibility of in-vivo needle-based forward-looking confocal laser endomicroscopy in prostate tissue. Methods: For this feasibility study, 2 patients with a suspicion of prostate cancer underwent transperineal needle-based confocal laser endomicroscopy during ultrasound-guided transperineal template mapping biopsies. After intravenous administration of fluorescein, needle-based confocal laser endomicroscopy imaging was performed with a forward-looking probe (outer diameter 0.9 mm) in 2 trajectories during a manual push-forward and pullback motion. A biopsy was taken in a coregistered parallel adjacent trajectory to the confocal laser endomicroscopy trajectory for histopathologic comparison. Peri- and postprocedural adverse events, confocal laser endomicroscopy device malfunction and procedural failures were recorded. Needle-based confocal laser endomicroscopy image quality assessment, image interpretation, and histology were performed by an experienced confocal laser endomicroscopy rater and uro-pathologist, blinded to any additional information. Results: In both patients, no peri- and post-procedural adverse events were reported following needle-based confocal laser endomicroscopy. No confocal laser endomicroscopy device malfunction nor procedural failures were reported. Within 1.5 min after intravenous administration of fluorescein, needle-based confocal laser endomicroscopy image quality was sufficient for interpretation for at least 14 min, yielding more than 5000 confocal laser endomicroscopy frames per patient. The pullback confocal laser endomicroscopy recordings and most of the push-forward recordings almost only visualized erythrocytes, being classified as non-representative. During the push-forward recordings, prostate tissue was occasionally visualized in single frames, insufficient for histopathologic comparison. Prostate carcinoma was identified by biopsy in one patient (Gleason score 4 + 3 = 7, >50%), while the biopsy from the other patient showed no malignancy. Conclusion: Needle-based confocal laser endomicroscopy imaging of in-vivo prostate tissue with a forward-looking confocal laser endomicroscopy probe is safe without device malfunctions or procedural failures. Needle-based confocal laser endomicroscopy is technically feasible, but the acquired confocal laser endomicroscopy datasets are non-representative. The confocal laser endomicroscopy images’ non-representative nature is possibly caused by bleeding artifacts, movement artifacts and a lack of contact time with the tissue of interest. A different confocal laser endomicroscopy probe or procedure might yield representative images of prostatic tissue.

Risk Stratification of Pancreatic Cysts With Confocal Laser Endomicroscopy

In the modern era of high-quality cross-sectional imaging, pancreatic cysts (PCs) are a common finding. The prevalence of incidental PCs detected on cross-sectional abdominal imaging (such as CT scan) is 3%–14% which increases with age, up to 8% in those 70 years or older. Although PCs can be precursors of future pancreatic adenocarcinoma, imaging modalities such as CT scan, MRI, or endoscopic ultrasound with fine-needle aspiration (EUS-FNA) are suboptimal at risk stratifying the malignant potential of individual cysts. An inaccurate diagnosis could potentially overlook premalignant lesions, which can lead to missed lesions, lead to unnecessary surveillance, or cause significant long-term surgical morbidity from unwarranted removal of benign lesions. Although current guidelines recommend an EUS or MRI for surveillance, they lack the sensitivity to risk stratify and guide management decisions. Needle-based confocal laser endomicroscopy (nCLE) with EUS-FNA can be a superior diagnostic modality for PCs with sensitivity and accuracy exceeding 90%. Despite this, a significant challenge to the widespread use of nCLE is the lack of adequate exposure and training among gastroenterologists for the real-time interpretation of images. Better understanding, training, and familiarization with this novel technique and the imaging characteristics can overcome the limitations of nCLE use, improving clinical care of patients with PCs. Here, we aim to review the types of CLE in luminal and nonluminal gastrointestinal disorders with particular attention to the evaluation of PCs. Furthermore, we discuss the adverse events and safety of CLE.

Cost-Benefit Analysis and Resource Implications of Endoscopic Ultrasound-Guided Confocal Endomicroscopy in Pancreatic Cysts

Background and AimsEUS-guided needle-based confocal laser endomicroscopy (nCLE) improves the diagnostic accuracy of pancreatic cystic lesions (PCLs) but concerns regarding its expense have limited widespread adoption of this technology. We conducted a cost-benefit analysis to assess the healthcare resource implications of adding EUS-nCLE to the standard of care (SOC) management of PCLs. MethodsA post-hoc analysis of a prospective study (2015-2018) evaluating EUS-nCLE for the diagnosis of PCLs was performed. The SOC diagnosis was based on clinical history, PCL morphology, and cyst fluid analysis. A minimum of 5-years surveillance was included, the cost of EUS and MRI/MRCP was derived from institutional billing data (US$), and the total hospital costs (adjusted for inflation) for pancreatic operations were derived from the National (US) Readmission Database. ResultsA reference diagnosis was available in 93 subjects (mean cyst size = 36.4 ± 15.7 mm; surgical histopathology, n = 67 and diagnostic molecular markers in cyst fluid, n = 26). SOC and nCLE were discordant in 13 (14%) subjects. The addition of nCLE led to 11 subjects being clinically down-staged from mucinous to non-mucinous not warranting surgery (total cost savings = $1,080,418), 1 subject upstaged from non-mucinous to mucinous, warranting surgical resection (cost savings of 5-years surveillance: $46,200), and 1 subject incorrectly classified as non-mucinous (cost excess of 5-years surveillance: $46,200). Overall, the addition of nCLE led to a net savings of $ 442,438 (mean: $ 4757.40/patient) for this cohort. ConclusionEUS-nCLE is potentially cost-beneficial in the management of PCLs (≥3 cm) by preventing at least one unnecessary pancreatic surgery for every 10 subjects undergoing evaluation by current practices. ClinicalTrials.gov number: NCT02516488.

Not your typical cyst: an evolving diagnosis

A 42-year-old man with a prior incidental finding of a lobulated cyst of the pancreatic head initially diagnosed as a pseudocyst underwent surveillance MRI, which showed enlargement of the cyst to 2.3 × 2.2 cm. That observation prompted EUS-FNA with needle-based confocal laser endomicroscopy (nCLE), which revealed the characteristic pattern of papillae suggestive of an intraductal papillary mucinous neoplasm (IPMN) (A). Fluid aspiration revealed an amylase level of >10,000 U/L, carcinoembryonic antigen (CEA) of 16 ng/mL, and a positive string sign.