A health economic evaluation of needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cysts

Abstract Background and study aims The low sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), especially for the diagnosis of serous cystadenomas (SCAs), can be associated with diagnostic uncertainty that can regularly lead to unnecessary surgical procedures. Needle-based confocal laser endomicroscopy (nCLE) used with EUS-FNA improves diagnostic accuracy, helping to reduce unnecessary surgery and patient follow-up. This study was conducted to evaluate the economic benefit of EUS-FNA + nCLE. Patients and methods Probabilities used were derived from two studies representative of the two diagnostic strategies: a retrospective analysis of patients diagnosed by EUS-FNA alone and a prospective study of patients diagnosed by EUS-FNA + nCLE. Costs were based on French healthcare system rates; both private and public sector rates were included. A decision tree structure model used these probabilities and costs for two hypothetical cohorts of 1000 patients. Results EUS-FNA + nCLE resulted in a reduction of 23 % in the total rate of surgical intervention, which translated to a reduction in clinical costs of 13 % (public sector) and 14 % (private sector). Additionally, the reduced rate of surgery would save the lives of 4 in 1000 patients. A stochastic sensitivity analysis using 100 simulations showed that in all cases the number of interventions was less for EUS-FNA + nCLE than for EUS-FNA. There was also a reduction in the incidence of false negatives using EUS-FNA + nCLE. Conclusions EUS-FNA + nCLE results in significant economic benefits by reducing the incidence of misdiagnosis through improved diagnostic accuracy.

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The Role of Confocal Endomicroscopy in the Diagnosis and Management of Pancreatic Cysts

European Medical Journal ◽

10.33590/emj/20-00182 ◽

2021 ◽

pp. 41-49

Author(s):

Margaret G Keane ◽

Stephen P Pereira

Keyword(s):

Diagnostic Accuracy ◽

Needle Aspiration ◽

Diagnostic Techniques ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Pancreatic Cysts ◽

Cystic Lesions ◽

Cystic Neoplasms ◽

Common Clinical Finding

Pancreatic cystic lesions are an increasingly common clinical finding. Current diagnostic techniques cannot reliably differentiate patients with high-risk lesions requiring surgical resection from those that can be safely surveyed or discharged. As a result, some patients may undergo unnecessary surgery with associated morbidity while others enter long-term surveillance with associated healthcare costs. Needle-based confocal laser endomicroscopy enables real time microscopic examination of the epithelial lining of a cyst wall at the time of a standard endoscopic ultrasound examination. The procedure is associated with low rates of adverse events, especially when the probe is loaded into the fine-needle aspiration needle before the procedure and examination times are limited. Needle-based confocal laser endomicroscopy has consistently been shown to have better diagnostic accuracy than cytology, which is often paucicellular and non-diagnostic in pancreatic cystic lesions. Studies have shown that diagnostic accuracy in needle-based confocal laser endomicroscopy is 84–95% in mucinous lesions and 39–99% in serous lesions. However, this technology is expensive and its place in diagnostic algorithms remains uncertain. Despite this, health economic analyses in certain health systems have been favourable, largely because of its potential to be able to discharge patients with benign lesions, such as serous cystic neoplasms, from long-term surveillance. Widespread adoption of this technology is unlikely but it has the potential to have an important role in indeterminate pancreatic cystic lesions.

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Deep learning systems detect dysplasia with human-like accuracy using histopathology and probe-based confocal laser endomicroscopy

Scientific Reports ◽

10.1038/s41598-021-84510-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shan Guleria ◽

Tilak U. Shah ◽

J. Vincent Pulido ◽

Matthew Fasullo ◽

Lubaina Ehsan ◽

...

Keyword(s):

Deep Learning ◽

Diagnostic Accuracy ◽

High Sensitivity ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Learning Approaches ◽

Learning Models ◽

Whole Slide Image ◽

Slide Image ◽

Level Model

AbstractProbe-based confocal laser endomicroscopy (pCLE) allows for real-time diagnosis of dysplasia and cancer in Barrett’s esophagus (BE) but is limited by low sensitivity. Even the gold standard of histopathology is hindered by poor agreement between pathologists. We deployed deep-learning-based image and video analysis in order to improve diagnostic accuracy of pCLE videos and biopsy images. Blinded experts categorized biopsies and pCLE videos as squamous, non-dysplastic BE, or dysplasia/cancer, and deep learning models were trained to classify the data into these three categories. Biopsy classification was conducted using two distinct approaches—a patch-level model and a whole-slide-image-level model. Gradient-weighted class activation maps (Grad-CAMs) were extracted from pCLE and biopsy models in order to determine tissue structures deemed relevant by the models. 1970 pCLE videos, 897,931 biopsy patches, and 387 whole-slide images were used to train, test, and validate the models. In pCLE analysis, models achieved a high sensitivity for dysplasia (71%) and an overall accuracy of 90% for all classes. For biopsies at the patch level, the model achieved a sensitivity of 72% for dysplasia and an overall accuracy of 90%. The whole-slide-image-level model achieved a sensitivity of 90% for dysplasia and 94% overall accuracy. Grad-CAMs for all models showed activation in medically relevant tissue regions. Our deep learning models achieved high diagnostic accuracy for both pCLE-based and histopathologic diagnosis of esophageal dysplasia and its precursors, similar to human accuracy in prior studies. These machine learning approaches may improve accuracy and efficiency of current screening protocols.

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Probe-based confocal laser endomicroscopy and Barrett's esophagus – just a scientific toy or significant improvement in diagnosis?

Digestive Diseases ◽

10.1159/000516257 ◽

2021 ◽

Author(s):

Luka Vranić ◽

Tin Nadarević ◽

Davor Štimac

Keyword(s):

Diagnostic Accuracy ◽

Real Time ◽

Barrett’S Esophagus ◽

Predictive Value ◽

Barrett's Esophagus ◽

High Reliability ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Imaging Method ◽

Increased Risk

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at early stage. Standard surveillance regimen includes random four-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patient. The main advantages would be real-time diagnosis and decision making, greater diagnostic accuracy and to evaluate larger area compared to random biopsies. Clinical pCLE studies in esophagus show high diagnostic accuracy and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key messages: Despite promising results, its role in routine use in patients with Barrett’s esophagus remains questionable primarily due to lack of well-organized double-blind randomized trials.

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Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis

Endoscopy ◽

10.1055/a-0732-5356 ◽

2018 ◽

Vol 51 (09) ◽

pp. 825-835 ◽

Cited By ~ 21

Author(s):

Bertrand Napoleon ◽

Maxime Palazzo ◽

Anne-Isabelle Lemaistre ◽

Fabrice Caillol ◽

Laurent Palazzo ◽

...

Keyword(s):

Diagnostic Performance ◽

Needle Aspiration ◽

Serous Cystadenoma ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Cystic Lesions ◽

Ultrasound Guided ◽

Cystic Fluid ◽

Post Procedure ◽

Mean Size

Abstract Background Needle-based confocal laser endomicroscopy (nCLE) enables observation of the inner wall of pancreatic cystic lesions (PCLs) during an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study prospectively evaluated the diagnostic performance of nCLE for large, single, noncommunicating PCLs using surgical histopathology or EUS-FNA cytohistopathology as a reference diagnosis. Methods From April 2013 to March 2016, consecutive patients referred for EUS-FNA of indeterminate PCLs without evidence of malignancy or chronic pancreatitis were prospectively enrolled at five centers. EUS-FNA and nCLE were performed and cystic fluid was aspirated for cytohistopathological and carcinoembryonic antigen (CEA) analysis. The diagnostic performance of nCLE was assessed against the reference standard and compared with that of EUS and CEA. This study was registered on ClinicalTrials.gov (NCT01563133). Results 206 patients underwent nCLE and 78 PCLs (mean size 40 mm, range 20 – 110 mm) had reference diagnoses (53 premalignant and 25 benign PCLs). Post-procedure pancreatitis occurred in 1.3 % of the patients. nCLE was conclusive in 71 of the 78 cases (91 %). The sensitivies and specifities of nCLE for the diagnosis of serous cystadenoma, mucinous PCL, and premalignant PCL were all ≥ 0.95 (with 95 % confidence interval from 0.85 to 1.0). The AUROC was significantly larger for nCLE than for CEA or EUS. Conclusions nCLE had excellent diagnostic performance that surpassed that of CEA and EUS for the diagnosis of large, single, noncommunicating PCLs. The nCLE procedure should be considered in patients with indeterminate PCLs to ensure a more specific diagnosis.

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PTU-156 The Combination of Autofluorescence Imaging and Probe-Based Confocal Laser Endomicroscopy has an Excellent Diagnostic Accuracy for Dysplasia in Barrett’S Esophagus

Gut ◽

10.1136/gutjnl-2013-304907.246 ◽

2013 ◽

Vol 62 (Suppl 1) ◽

pp. A111.3-A112

Author(s):

M Di Pietro ◽

E Bird-Lieberman ◽

X Liu ◽

M O’Donovan ◽

R C Fitzgerald

Keyword(s):

Diagnostic Accuracy ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Autofluorescence Imaging

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The Impact of Repeating Endosonography with Confocal Endomicroscopy for the Diagnosis of Cystic Neuroendocrine Tumor

Case Reports in Gastrointestinal Medicine ◽

10.1155/2019/5187874 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Iqra Haq ◽

Somashekar G. Krishna ◽

Bhaveshkumar Patel ◽

Thavam Thambi-Pillai ◽

Chencheng Xie ◽

...

Keyword(s):

Neuroendocrine Tumor ◽

Neuroendocrine Tumors ◽

Pancreatic Pseudocyst ◽

Incidental Finding ◽

Pancreatic Neuroendocrine Tumor ◽

Needle Aspiration ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

The Impact

Cystic pancreatic neuroendocrine tumors represent around 13% of all neuroendocrine tumors (Hurtado-Pardo 2017). There has been an increase in the incidence of cases due to improvement in imaging modalities. This is a case of a 68-year-old male with the incidental finding of a pancreatic cyst on CT. Initial Endoscopic Ultrasound with Fine Needle Aspiration (EUS-FNA) showed sonographic and cytology features suggestive of a pancreatic pseudocyst. However the cyst persisted with no change in size after aspiration leading to a follow-up EUS- FNA, which was combined with needle based confocal laser endomicroscopy (nCLE). The nCLE features were consistent with a cystic pancreatic neuroendocrine tumor, which was later confirmed on histology after surgical resection.

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Endoscopic ultrasound guided needle-based confocal laser endomicroscopy in solid pancreatic masses – a prospective validation study

Endoscopy International Open ◽

10.1055/s-0043-121987 ◽

2018 ◽

Vol 06 (01) ◽

pp. E78-E85 ◽

Cited By ~ 10

Author(s):

John Karstensen ◽

Tatiana Cârţână ◽

Codruţa Constantinescu ◽

Silviu Dumitrașcu ◽

Bojan Kovacevic ◽

...

Keyword(s):

Endoscopic Ultrasound ◽

Final Diagnosis ◽

Diagnostic Value ◽

Needle Aspiration ◽

Observer Agreement ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Dark Cell ◽

Pancreatic Masses ◽

Pass Through

Abstract Background and study aims Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is a keystone in diagnosing and staging of pancreatic masses. Recently, a microfiber that can pass through a 19-gauge needle has been introduced for confocal laser endomicroscopy (nCLE). The aims of this study were to evaluate the diagnostic value and the reproducibility of nCLE criteria for solid malignant lesions. Patients and methods This prospective dual-center study included patients with pancreatic masses suspicious of malignancy referred for EUS-FNA. Endomicroscopic imaging was performed under EUS-guidance until organ-specific structures were obtained. Afterwards, standard cytology was obtained and patients were followed for up to 12 months. All nCLE parameters included in former studies were correlated with the final diagnosis (dark lobular structures/normal acinar cells, dark cell aggregates > 40 µm, dilated irregular vessels with fluorescein leakage, fine white fibrous bands, small black cell movements, pseudoglandular structures). Finally, three CLE novices and three CLE experts assessed the unedited movies from all patients. Results Twenty-eight patients were enrolled in the study. A final diagnosis was obtained in 24 patients (86 %). One patient (3 %) died before a diagnosis was obtained, while 3 were lost to follow-up (11 %). In 18/24 patients (74 %) the diagnosis was malignant. The mean sensitivity, specificity, and accuracy for the nCLE parameters ranged from 19 – 93 %, 0 – 56 %, 26 – 69 %, respectively. The inter-observer values ranged from κ = 0.20 – 0.41 for novices and κ = –0.02 – 0.38 for experts. Conclusions The diagnostic value of nCLE in solid pancreatic masses is questionable and the inter-observer agreement for both novices and CLE experts appears limited.

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