Uses of probe-based confocal laser endomicroscopy:Responses to a question to practitioners

Confocal laser endomicroscopy is a novel imaging technology,which allows realtime visualization and inter-pretation of microscopic details in live tissues. Although several potential uses have been identified for this technology,no data are available regarding its real-worlduses. We report the results of an email-based survey of experts in North America regarding their use of the technology.

Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy:A case report

BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Confocal laser endomicroscopy as a new diagnostic tool for poorly differentiated gastric adenocarcinoma

Gastric cancer(GC)is a multifactorial disease,where both environmental and genetic features can have an impact on its occurrence and development.GC represents one of the leading causes of cancer-related deaths worldwide.GC is most frequent in males and is believed to arise from a series of premalignant lesions.The detection of GC at an early stage is crucial because early GC,which is an invasive stomach cancer confined to the mucosal or submucosal lining,may be curable with a reported 5-year survival rate of more than 90%.Advanced GC usually has a poor prognosis despite current treatment standards.The diagnostic efficacy of conventional endoscopy(with light endoscopy)is currently limited.Confocal laser endomicroscopy is a novel imaging technique that allows real-time in vivo histological examination of mucosal surfaces during endoscopy.Confocal laser endomicroscopy may be of great importance in the surveillance of precancerous gastric lesions and in the diagnosis of GC.In this editorial we commented on the article about this topic published by Lou et al in the recent issue of the World Journal of Clinical Cases.

Confocal laser endomicroscopy for gastric neoplasm

Confocal laser endomicroscopy(CLE)is a novel endoscopic modality that provides real-time histological information via high-resolution magnified view of the mucosa.CLE has a higher sensitivity,specificity,and diagnostic accuracy in detecting atrophic gastritis as compared to chromoendoscopy and narrow-band imaging.It can even predict low-grade and high-grade intraepithelial neoplasia by analyzing gastric pit patterns.CLE may have some advantages over the standard biopsy protocol,such as higher diagnostic yield and fewer biopsy requirements.Its diagnostic accuracy in detecting superficial gastric cancer is higher than that of white-light endoscopy.Inherent limitations,such as a narrow field of vision,can be surpassed by technological advancements and integration with other detection methods.Artificial intelligence holds promise in automated analysis of histopathological images.Thus,CLE can be helpful in screening for early gastric cancer and may help reduce the risk of complications from repeated biopsies,such as mucosal damage,bleeding,and infection.

Confocal Laser Endomicroscopy in the Field of Esophageal Diseases

Confocal laser endomicroscopy (CLE) is a new endoscopic imaging technology that allows real-time, high-resolution observation of tomographic images of mucosal cells and subcellular levels in vivo, detecting microscopic structural changes in mucosal morphology, and its in vivo immediate pathological diagnostic capability can avoid delays in mucosal pathological diagnosis and reduce the pain caused by repeated biopsies. CLE is known as “optical biopsy” and compared with other endoscopic techniques, it has obvious advantages. CLE systems include probe-based confocal laser endomicroscopy (pCLE) and endoscope-based confocal laser endomicroscopy (eCLE). Since 2006, CLE has been widely used for the evaluation of various lesions in the digestive system, including esophageal, gastric, and colonic neoplasia, pancreatic cysts and solid lesions, and inflammatory bowel disease. The advent of CLE has made in vivo microscopic imaging possible, which has changed the endoscopic screening and diagnosis of multiple gastrointestinal (GI) lesions. However, the value of its use in GI diseases is still controversial. In this review, we focus on the application of CLE in the field of esophageal diseases.

Real-time in vivo distal margin selection using confocal laser endomicroscopy in transanal total mesorectal excision for rectal cancer

BACKGROUND Transanal total mesorectal excision(TaTME)allows patients with ultralow rectal cancer to be treated with sphincter-saving surgery.However,accurate delineation of the distal resection margin(DRM),which is essential to achieve R0 resection for low rectal cancer in TaTME,is technically demanding.AIM To assess the feasibility of optical biopsy using probe-based confocal laser endomicroscopy(pCLE)to select the DRM during TaTME for low rectal cancer.METHODS A total of 43 consecutive patients who were diagnosed with low rectal cancer and scheduled for TaTME were prospectively enrolled from January 2019 to January 2021.pCLE was used to determine the distal edge of the tumor as well as the DRM during surgery.The final pathological report was used as the gold standard.The diagnostic accuracy of pCLE examination was calculated.RESULTS A total of 86 pCLE videos of 43 patients were included in the analyses.The sensitivity,specificity and accuracy of real-time pCLE examination were 90.00%[95%confidence interval(CI):76.34%-97.21%],86.96%(95%CI:73.74%-95.06%)and 88.37%(95%CI:79.65%-94.28%),respectively.The accuracy of blinded pCLE reinterpretation was 86.05%(95%CI:76.89%-92.58%).Furthermore,our results show satisfactory interobserver agreement(κ=0.767,standard error=0.069)for the detection of cancer tissue by pCLE.There were no positive DRMs(≤1 mm)in this study.The median DRM was 7 mm[interquartile range(IQR)=5-10 mm].The median Wexner score was 5(IQR=3-6)at 6 mo after stoma closure.CONCLUSION Real-time in vivo pCLE examination is feasible and safe for selecting the DRM during TaTME for low rectal cancer(clinical trial registration number:NCT04016948).

Classification of histological severity of Helicobacter pylori-associated gastritis by confocal laser endomicroscopy

AIM: To classify the histological severity of Helicobacter pylori (H. pylori) infection-associated gastritis by confocal laser endomicroscopy (CLE). METHODS: Patients with upper gastrointestinal symptoms or individuals who were screened for gastric cancer were enrolled in this study. Histological severity of H. pylori infection-associated gastritis was graded according to the established CLE criteria. Diagnostic value of CLE for histo-logical gastritis was investigated and compared with that of white light endoscopy (WLE). Targeted biopsies from the sites observed by CLE were performed. RESULTS: A total of 118 consecutive patients with H. pylori infection-associated gastritis were enrolled in this study. Receiver operating characteristic curve analysis showedthat the sensitivity and specifi city of CLE were 82.9% and 90.9% for the diagnosis of H. pylori infection, 94.6% and 97.4% for predicting gastric normal mucosa, 98.5% and 94.6% for predicting histological active inflammation, 92.9% and 95.2% for predicting glan-dular atrophy, 98.6% and 100% for diagnosing intes-tinal metaplasia, respectively. Post-CLE image analysis showed that goblet cells and absorptive cells were the two most common parameters on the CLE-diagnosed intestinal metaplasia (IM) images (P < 0.001). More his-tological lesions of the stomach could be found by CLE than by WLE (P < 0.001). CONCLUSION: CLE can accurately show the histological severity of H. pylori infection-associated gastritis. Mapping IM by CLE has a rather good diagnostic accuracy.

Probe based confocal laser endomicroscopy of the pancreatobiliary system

AIM:To review applications of confocal laser endomicroscopy(CLE) in pancreatobiliary lesions and studies that assessed training and interpretation of images. METHODS: A computerized literature search was performed using OVID MEDLINE, EMBASE, Cochrane library, and the ISI Web of Knowledge from 1980 to October 2014. We also searched abstracts from major meetings that included the Digestive Disease Week, Canadian Digestive Disease Week and the United European Gastroenterology Week using a combination of controlled vocabulary and text words related to p CLE, confocal, endomicroscopy, probe-based confocal laser endomicroscopy, and bile duct to identify reports of trials. In addition, recursive searches and crossreferencing was performed, and manual searches of articles identified after the initial search was also completed. We included fully published articles and those in abstract form. Given the relatively recent introduction of CLE we included randomized trials and cohort studies.R E S U LT S : In the evaluation of indeterminate pancreatobiliary strictures CLE with ERCP compared to ERCP alone can increase the detection of cancerous strictures with a sensitivity of(98% vs 45%) andhas a negative predictive value(97% vs 69%), but decreased the specificity(67% vs 100%) and the positive predictive value(71% vs 100%) when compared to index pathology. Modifications in the classification systems in indeterminate biliary strictures have increased the specificity of p CLE from 67% to 73%. In pancreatic cystic lesions there is a need to develop similar systems to interpret and characterize lesions based on CLE images obtained. The presence of superficial vascular network predicts serous cystadenomas accurately. Also training in acquiring and interpretation of images is feasible in those without any prior knowledge in CLE in a relatively simple manner and computer-aided diagnosis software is a promising innovation. CONCLUSION: The role of p CLE in the evaluation of pancreatobiliary disorders might be better suited for those with an intermediate and low probability.

Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.

Confocal laser endomicroscopy and immunoendoscopy for real-time assessment of vascularization in gastrointestinal malignancies

Gastrointestinal cancers represent a major cause of morbidity and mortality,with incomplete response to chemotherapy in the advanced stages and poor prognosis.Angiogenesis plays a crucial part in tumor growth and metastasis,with most gastrointestinal cancers depending strictly on the development of a new and devoted capillary network.Confocal laser endomicroscopy is a new technology which allows in vivo microscopic analysis of the gastrointestinal mucosa and its microvascularization during ongoing endoscopy by using topically or systemically administered contrast agents.Targeting markers of angiogenesis in association with confocal laser endomicroscopic examination(immunoendoscopy),as a future challenge,will add functional analysis to the morphological aspect of the neoplastic process.This review describes previous experience in endomicroscopic examination of the upper and lower digestive tract with emphasis on vascularization,resulting in a broad spectrum of potential clinical applications,and also preclinical research that could be translated to human studies.

Molecular confocal laser endomicroscopy:A novel technique for in vivo cellular characterization of gastrointestinal lesions

While flexible endoscopy is essential for macroscopic evaluation,confocal laser endomicroscopy(CLE)has recently emerged as an endoscopic method enabling visualization at a cellular level.Two systems are currently available,one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound.The second system has a confocal microscope integrated into the distal part of an endoscope.By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure(either topically or systemically administered during on-going endoscopy),a novel world of molecular evaluation opens up.The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas,subsequently resulting in immediate individualization of treatment regimens,but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions.Furthermore,studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ,which probably can be correlated to the efficacy of the drug.However,several of the studies in this research field have been conducted in animal facilities or in vitro,while only a limited number of trials have actually been carried out in vivo.Therefore,safety issues still needs further evaluations.This review will present an overview of the implications and pitfalls,as well as future challenges of molecular CLE in gastrointestinal diseases.

Clinical impact of confocal laser endomicroscopy in the management of gastrointestinal lesions with an uncertain diagnosis

To evaluate the clinical impact of confocal laser endomicroscopy (CLE) in the diagnosis and management of patients with an uncertain diagnosis. METHODSA retrospective chart review was performed. Patients who underwent CLE between November 2013 and October 2015 and exhibited a poor correlation between endoscopic and histological findings were included. Baseline characteristics, indications, previous diagnostic studies, findings at the time of CLE, clinical management and histological results were analyzed. Interventions based on CLE findings were also analyzed. We compared the diagnostic accuracy of CLE and target biopsies of surgical specimens. RESULTSA total of 144 patients were included. Of these, 51% (74/144) were female. The mean age was 51 years old. In all, 41/144 (28.4%) lesions were neoplastic (13 bile duct, 10 gastric, 8 esophageal, 6 colonic, 1 duodenal, 1 rectal, 1 ampulloma and 1 pancreatic). The sensitivity, specificity, positive predictive value, negative predictive value, and observed agreement when CLE was used to detect N-lesions were 85.37%, 87.38%, 72.92%, 93.75% and 86.81%, respectively. Cohen’s Kappa was 69.20%, thus indicating good agreement. Changes in management were observed in 54% of the cases. CONCLUSIONCLE is a new diagnostic tool that has a significant clinical impact on the diagnosis and treatment of patients with uncertain diagnosis.

Confocal laser endomicroscopy distinguishing benign and malignant gallbladder polyps during choledochoscopic gallbladderpreserving polypectomy:A case report

BACKGROUND In the last decade, confocal laser endomicroscopy (CLE) has emerged as a newendoscopic imaging modality for real-time in vivo histological examination at themicroscopic level. CLE has been shown to be useful for distinguishing benign andmalignant lesions and has been widely used in many digestive diseases. In ourstudy, we used CLE for the first time to examine the morphology of cholesterolpolyps as well as the different parts of normal gallbladder mucosa.CASE SUMMARY A 57-year-old woman was diagnosed by ultrasound with a polyp of 21 mm in thegallbladder wall. She consented to polyp removal by laparoscopic choledochoscopy.During laparoscopic cholecystectomy combined with choledochoscopicpolyp resection, CLE was used to observe the morphology of the polyp surfacecells. The appearance of the mucosa and microvessels in various parts of thegallbladder were also observed under CLE. Through comparison betweenpostoperative pathology and intraoperative CLE diagnosis, the reliability ofintraoperative CLE diagnosis was confirmed. CLE is a reliable method to examineliving cell pathology during cholecystectomy. Based on our practice, CLE shouldbe prioritized in the diagnosis of gallbladder polyps.CONCLUSION Compared with traditional histological examination, CLE has several advantages.We believe that CLE has great potential in this field.

Appraisal of needle-based confocal laser endomicroscopy inthe diagnosis of pancreatic cysts

Nearly 2.5% of cross-sectional imaging studies will report a finding of a cystic pancreatic lesion. Eventhough most of these are incidental findings, it remains very concerning for both patients and treating clinicians. Differentiating and predicting malignant transformation in pancreatic cystic lesions is clinically challenging. Current evaluation of suspicious cystic lesions includes a combination of radiologic imaging, endoscopic ultrasound(EUS) and cyst fluid analyses. Despite these attempts, precise diagnostic stratification among nonmucinous, mucinous, and malignant cystic lesions is often not possible until surgical resection. EUS-guided needle based confocal laser endomicroscopy(n CLE) for evaluation of pancreatic cysts is emerging as a powerful technique with remarkable potential. Though limited imaging data from 3 large clinical trials(INSPECT, DETECT and CONTACT) are currently the reference standard for n CLE imaging, nonetheless these have not been validated in large studies. The aim of this review article is to review the evolving role of EUS-guided n CLE in management of pancreatic cystic lesions in terms of its significance, adverse events, limitations, and implications.

Confocal laser endomicroscopy in inflammatory bowel diseases:Dream or reality?

Confocal laser endomicroscopy(CLE)is a newly introduced procedure that provide real-time,high-resolution imaging of the gastrointestinal mucosa during endoscopy,allowing the visualization of the pathology of the mucosal epithelium with its cellular and subcellular structures.Recently,the use of CLE was reported in the study of colonic mucosa in patients with inflammatory bowel diseases and in particular in patients affected by ulcerative colitis.CLE has the potential to have an important role in management of inflammatory bowel diseases(IBD)patients as it can be used to assess the grading of colitis and in detection of microscopic colitis in endoscopically silent segments.Moreover,CLE can be used in surveillance programs especially in highrisk patients.Finally,CLE has been effectively used in diagnosing a biliary dysplasia/neoplasia in patients with primary sclerosing cholangitis,a pathological condition frequently associated with IBD,with a coexisting bile duct stricture.

Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probebased confocal laser endomicroscopy of the normal stomach

Probe-based confocal laser endomicroscopy(p CLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. p CLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared with that after 1 min. The presence of fluorescein in the mucosa was observed within a short time after local mucosal application of fluorescein, suggesting that pC LE images similarly to those after intravenous fluorescein administration can be acquired by local mucosal application of fluorescein.

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody:Pilot study

AIM: To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy(CLE).METHODS: CLE is an imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution.An important question in validating tumor angiogenesis is what proportion of the tumor vascular network is represented by preexisting parent tissue vessels and newly formed vessels.CD105(endoglin) represents a proliferation-associated endothelial cell adhesion molecule.In contrast to panendothelial markers,such as CD31,CD105 is preferentially expressed in activated endothelial cells that participate in neovascularization.Thus,we evaluated CD105 and CD31 expression from samples of ten patients with primary rectal adenocarcinoma,using a dedicated endomicroscopy system.A imaging software was used to obtain the Z projection of the confocal serial images from each biopsy sample previously combined into stacks.Vascular density and vessel diameters were measured within two 50 μm x 475 μm rectangular regions of interest centered in the middle of each image in the horizontal and vertical direction.The results were averaged over all the patients and were expressed as the mean ± SE.RESULTS: The use of an anti-CD105 antibody was found to be suitable for the detection of blood vessels in colon cancer.Whereas anti-CD31 antibodies stained blood vessels in both normal and pathologic colon equally,CD105 expression was observed primarily in malignant lesions,with little or no expression in the vessels of the normal mucosa(244.21 ± 130.7 vessels/mm3 in only four patients).The average diameter of antiCD105 stained vessels was 10.97 ± 0.6 μm in tumor tissue,and the vessel density was 2787.40 ± 134.8 vessels/mm3.When using the anti-CD31 antibody,the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 μm and the vessel density was 3191.60 ± 387.8 vessels/mm3,while in the tumors we obtained an average diameter of 10.88 ± 0.8 μm and a vessel density of 4707.30 ± 448.85 vessels/mm3.Thus,there were more vessels stained with CD31 than CD105(P < 0.05).The average vessel diameter was similar for both CD31 and CD105 staining.A qualitative comparison between CLE vs immunohistochemistry lead to similar results.CONCLUSION: Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples.

Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders

AIM： To evaluate the feasibility and utility of confocal laser endomicroscopy （CLE） in the description of normal gastrointestinal （GI） mucosa and in the diagnosis of GI disorders in children, in comparison to histology.METHODS： Forty-four patients （19 female） median age 10.9 years （range 0.7-16.6 years） with suspected or known GI pathology underwent esophago-gastro- duodenoscopy （OGD） （n = 36） and/or ileocolonoscopy （IC） （n = 31） with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively.RESULTS： Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min （range 7-25 rain） for OGD and 27.9 min （range 15-45 min） for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures.Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease.CONCLUSION： CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs.

Confocal endomicroscopy:Is it time to move on?

Confocal laser endomicroscopy permits in-vivo microscopy evaluation during endoscopy procedures. It can be used in all the parts of the gastrointestinal tract and includes: Esophagus,stomach,small bowel,colon,biliary tract through and endoscopic retrograde cholangiopancreatography and pancreas through needles during endoscopic ultrasound procedures. Many researches demonstrated a high correlation of results between confocal laser endomicroscopy and histopathology in the diagnosis of gastrointestinal lesions; with accuracy in about 86% to 96%. Moreover,in spite that histopathology remains the gold-standard technique for final diagnosis of any diseases; a considerable number of misdiagnosis rate could be present due to many factors such as interpretation mistakes,biopsy site inaccuracy,or number of biopsies. Theoretically; with the diagnostic accuracy rates of confocal laser endomicroscopy could help in a daily practice to improve diagnosis and treatment management of the patients. However,it is still not routinely used in the clinical practice due to many factors such as cost of the procedure,lack of codification and reimbursement in some countries,absence of standard of care indications,availability,physician imageinterpretation training,medico-legal problems,and the role of the pathologist. These limitations are relative,and solutions could be found based on new researches focused to solve these barriers.

In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study

To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs).METHODSIn a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively.RESULTSA total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a “fern pattern” of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology.CONCLUSIONIn vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.