INTRODUCTION — Confocal laser endomicroscopy and endocytoscopy are endoscopic technologies that permit high-resolution assessment of gastrointestinal mucosal histology at a cellular and sub-cellular level. Endomicroscopy and endocytoscopy dramatically expand the imaging capabilities of flexible endoscopy by their ability to obtain "optical biopsies" of nearly any accessible endoluminal surface.
The examinations are carried out in vivo with real-time image display. The techniques have primarily been applied to the differentiation of colon polyps and for the detection of dysplasia and neoplasia in conditions such as Barrett's esophagus and ulcerative colitis. Since the first visible neoplastic changes in epithelial cancers occur at a cellular level, these imaging techniques may allow for earlier diagnosis and treatment. In addition, confocal laser endomicroscopy and endocytoscopy may allow for targeted biopsies of abnormal mucosa, thereby decreasing the number of biopsies required to diagnose dysplasia or neoplasia while increasing diagnostic yield.
This topic will review confocal laser endomicroscopy and endocytoscopy, including the technical aspects of the procedures, their indications, and efficacies. Chromoendoscopy, magnification endoscopy, optical coherence tomography, and narrow band imaging are discussed elsewhere. (See "Chromoendoscopy" and "Magnification endoscopy" and "Optical coherence tomography in the gastrointestinal tract" and "Barrett's esophagus: Evaluation with optical chromoscopy".)
TECHNICAL OVERVIEW
Confocal laser endomicroscopy — Confocal laser endomicroscopy (CLE) is based upon the principle of illuminating a tissue with a low-power laser and then detecting fluorescent light reflected from the tissue [1]. The laser is focused at a specific depth and only light reflected back from that plane is refocused and able to pass through the pinhole confocal aperture. As a result, scattered light from above and below the plane of interest is not detected, increasing spatial resolution. The area being examined is scanned in the horizontal and vertical planes and an image is reconstructed. In this manner, microscopic imaging of biologic tissue in vivo is possible due to the high lateral resolution of confocal imaging.
Since CLE relies upon tissue fluorescence, intravenous and/or topically applied contrast agents are required. Intravenous fluorescein is used to highlight the vasculature, lamina propria, and intracellular spaces of this tissue being examined. However, it does not stain cell nuclei. Nuclear staining can be achieved using topical contrast agents such as acriflavine and cresyl violet, but there is concern over mutagenic potential with the topical agents. (See 'Adverse events' below.)
The greatest challenge for CLE has been miniaturization and integration of the technology into endoscopic equipment. Two systems have been approved by the US Food and Drug Administration: a tip-integrated confocal laser endomicroscope and a flexible fiber-based confocal miniprobe. Both systems contain a laser scanning unit and a PC-based image viewer for image acquisition and storage. Of note, only the confocal miniprobe is commercially available.
Confocal laser endomicroscope — Endoscope-based confocal laser endomicroscopy (eCLE) uses a miniaturized confocal laser endomicroscope that is integrated into the distal tip of a conventional endoscope [1]. However, these confocal laser endomicroscopes with a tip-integrated solution are no longer commercially available.
Confocal miniprobe — A flexible probe-based system (Cellvizio, Mauna Kea Technologies, Paris, France) is an alternative to using a confocal laser endomicroscope [1]. In probe-based confocal laser endomicroscopy (pCLE), both the laser scanning unit and light source are outside the body of the patient, making the confocal miniprobe a "passive" conduit. Multiple probes are available that vary with regard to field of view, depth of confocal plane, and lateral resolution.
The miniprobes are very flexible and can be passed through the working channel of a standard endoscope. Their diameters range from 0.9 to 2.5 mm. The probes can be disinfected and reused, but the number of uses is limited (approximately 20). Other accessories, such as a hood on the tip of an endoscope or endoscopic retrograde cholangiopancreatography accessories, may be helpful, but are not mandatory. (See 'Maximizing image quality' below.)
The 488 nm laser beam is transmitted via several thousand optical fibers within the probe. These same fibers return the reflected fluorescent light to a distal micro-objective. Confocal image data are collected at a frame rate of 12 frames per second that, unlike eCLE at 0.8 to 1.6 frames per second, enables video quality. Depending upon which probe is used, the field of view ranges from 240 x 240 microns to 600 x 500 microns, the lateral resolution ranges from 1 to 3.5 microns, and the depth of imaging ranges from 0 to 100 microns. In pCLE, the depth of imaging depends upon the probe being used.
An advantage of pCLE is that probes have been developed for biliary and pancreatic examinations. The Cholangioflex-probe has a diameter of 0.9 mm and can be passed through the instrumentation channel of a cholangioscope [2]. During cholangioscopy, the probe can be placed against the lesion or area of interest under direct visual control and guidance. There are also reports of the probe being passed under fluoroscopic guidance using endoscopic retrograde cholangiopancreatography catheters [3,4]. The tip of the probe has a metallic ring and can be easily seen on fluoroscopy (see "Cholangioscopy and pancreatoscopy" and "Percutaneous transhepatic cholangioscopy").
With further miniaturization of the device, miniprobes can meanwhile be passed through a 19-gauge needle used for fine needle aspiration, thereby enabling endoscopic ultrasound-guided CLE of solid organs, lymph nodes, and cystic lesions.
Endocytoscopy — Similar to confocal laser endomicroscopy (CLE), endocytoscopy aims to enable real-time microscopic imaging of the mucosa in vivo. The main difference between CLE and endocytoscopy is that endocytoscopy is based solely on high-level magnification using optical lenses. Therefore, because there is no confocal plane, only the very superficial layer of the mucosa can be imaged. In addition, the lens must come into direct contact with the tissue being examined.
An endocytoscopy system is manufactured by Olympus (Tokyo, Japan). The system can be probe-based [5,6] or integrated within an endoscope [7,8]. The probe-based system consists of two flexible catheters that provide surface magnification of 450- and 1125-fold with a 14-inch monitor or 570- and 1400-fold using a 19-inch monitor. The endocytoscopy system integrated within an endoscope is the only type that is commercially available.
As with confocal endomicroscopy, acquisition of quality images requires application of a contrast agent. Typically, topical application of methylene blue or a combination of methylene blue with crystal violet is used [7,9]. In epithelia that produce significant amounts of mucin (eg, gastric epithelium or Barrett's mucosa), imaging may be hampered by the contrast agent failing to penetrate the mucin barrier, resulting in inadequate staining. (See 'Staining' below.)
Additionally, endocytoscopy has been combined with an artificial intelligence system that is able to differentiate dysplastic/adenomatous polyps from hyperplastic polyps with high accuracy [10].
Maximizing image quality — The keys to obtaining high-quality images are optimizing contrast administration, positioning, and stability.
Staining — Image quality following intravenous fluorescein administration is best within the first 10 minutes following contrast administration [11], though imaging may continue for 30 to 45 minutes [12,13]. For examinations using topical contrast agents, it is essential to thoroughly remove the mucin layer prior to staining. This can be done by applying N-acetylcysteine or acetic acid, flushing with water, and then homogeneously staining the mucosa using a spraying catheter.
Device placement — To improve image quality, when possible, the probe or endoscope should be placed perpendicular to the mucosa rather than tangentially. The way the device is placed is also important in patients with friable lesions because blood causes visual interference. In such cases, the probe or endoscope should be carefully placed in apposition to the mucosa to decrease tissue disruption.
Stabilization — Movements caused by the examiner or the patient (breathing or peristalsis) can impair positioning and cause artifacts. For probe-based examinations, attaching a clear plastic cap to the tip of the endoscope and applying gentle suction helps hold the probe in position. Such an approach can be particularly helpful when imaging Barrett's esophagus since probe placement in the distal esophagus can be challenging. In addition, using propofol to sedate the patient helps to avoid retching, belching, and patient movement during the procedure. (See "Anesthesia for gastrointestinal endoscopy in adults".)
Obtaining biopsies — The eCLE scope has a regular working channel that is not occupied by a probe, and a biopsy can be taken from the same area. On the other hand, with pCLE systems the miniprobes occupy the working channel of the endoscope, so biopsies can only be obtained after the probe is removed. This limitation can be overcome by creating a suction polyp that contains the area of interest. In the case of cholangioscopy, after the lesion or area of interest has been examined, the probe is removed and a biopsy forceps is passed through the biopsy channel of the cholangioscope.
INDICATIONS — The indications for confocal laser endomicroscopy (CLE) and endocytoscopy are still being defined. In general, these procedures are used to target biopsies of abnormal tissue and decrease biopsies of normal tissue. The goal is to increase diagnostic yield, while minimizing procedure-related risks of tissue acquisition. A potential indication that has not yet been evaluated is using "optical biopsies" with these techniques instead of conventional histology in patients at high risk for procedure-associated bleeding. (See "Gastrointestinal endoscopy in patients with disorders of hemostasis".)
CLE and endocytoscopy have been used to:
●Differentiate neoplastic from non-neoplastic colon polyps and lesions (colon and stomach)
●Detect dysplasia and neoplasia in patients undergoing surveillance for Barrett's esophagus or ulcerative colitis
●Differentiate benign from malignant biliary strictures
●Guide endoscopic mucosal resection of dysplastic lesions in Barrett's esophagus (see "Barrett's esophagus: Treatment of high-grade dysplasia or early cancer with endoscopic resection")
●Potentially detect celiac disease
With further miniaturization of confocal miniprobes, it has become possible to perform CLE via the needles used for endoscopic ultrasound-guided fine needle aspiration [14]. This may permit improved diagnostic accuracy of cystic pancreatic lesions [15]. (See 'Cystic lesions of the pancreas' below.)
CLE (and to some extent endocytoscopy) may also have a role in the evaluation of organs outside the gastrointestinal tract. Probe-based CLE has been used for the detection and classification of chronic pulmonary disease [16]. In addition, probe-based CLE and endocytoscopy have been applied for the detection of bladder cancer via a transurethral approach [17,18].
CONTRAINDICATIONS — The primary contraindication to confocal laser endomicroscopy and endocytoscopy is an allergy to the contrast agent being used. In addition, patients must be deemed fit candidates for endoscopy. (See 'Adverse events' below.)
EFFICACY — There are a limited but increasing number of studies evaluating the accuracy of confocal laser endomicroscopy [1]. Fewer studies have been performed with endocytoscopy. In general, most reported results have been good, with accuracy rates ranging between 80 and 95 percent. However, almost all of these studies were performed in centers with significant experience in endoscopic imaging technologies. The patients were highly selected, and the examiners in many studies were not blinded to other relevant clinical and endoscopic data. Furthermore, studies comparing CLE with other imaging techniques, such as narrow band imaging, are rare. Thus, further studies are needed to confirm the initially promising results.
Efficacy of confocal laser endomicroscopy — Confocal laser endomicroscopy (CLE) has been studied for use in the upper and lower gastrointestinal (GI) tract, as well as in the hepatobiliary tree:
●Upper GI applications have included detection of neoplasia in the esophagus and stomach, identification of Helicobacter pylori in the stomach [19], and detection of villous atrophy and increased intraepithelial lymphocytes in the small bowel of patients with celiac disease [20-27].
●The primary focus on CLE in the lower GI tract has been for the differentiation of neoplastic from non-neoplastic polyps. CLE has also been used to detect disease activity and dysplasia in patients with chronic ulcerative colitis and to diagnose microscopic colitis [28,29].
●In the hepatobiliary tree, CLE has been used to differentiate benign from malignant strictures.
●Preliminary data suggest needle-based CLE may be helpful for differentiation of pancreatic cystic lesions.
●CLE has been used for diagnosing atypical food allergies characterized by an early and increased leakage of fluorescein [30].
Barrett's esophagus — Compared with normal columnar esophageal epithelium, Barrett's epithelium is characterized on CLE by a more tubular shaped mucosa, with a regular and constant width of the epithelial layer (image 1). In addition, goblet cells, which are not seen in normal columnar esophagus, can be identified. Findings suggestive of neoplasia include a loss of the normal epithelial architecture, a variable epithelial layer width, a dark epithelial appearance, and the presence of irregular vasculature with leakage of fluorescein.
Studies of the sensitivity and specificity of CLE in detecting neoplasia in patients with Barrett's esophagus have had variable results [31-39]. However, most studies suggest the sensitivity is at least 70 percent, and the specificity is at least 90 percent. The diagnostic yield with CLE was examined in a randomized trial with 192 patients with Barrett's esophagus who were assigned to either undergo high-definition white-light endoscopy and CLE with targeted biopsies or high-definition white-light endoscopy with random biopsies [39]. The diagnostic yield for neoplasia was higher among the patients who underwent CLE with targeted biopsies compared with those who had random biopsies (22 versus 6 percent).
Due to its deeper confocal imaging plane, CLE appears to be superior to endocytoscopy for the evaluation Barrett's esophagus and gastric neoplasia. (See 'Stomach and columnar esophagus' below.)
CLE has also been used to guide endoscopic mucosal resection (EMR) in patients with Barrett's esophagus. In a study of 62 such patients, 22 had flat high-grade dysplasia by CLE and underwent EMR [36]. Histopathology revealed low-grade dysplasia in six, high-grade dysplasia in 12, and no dysplasia in four. The sensitivity of CLE for dysplasia was 94 percent, with a specificity of 50 percent. By contrast, in another study aimed to assess if the use of pCLE in addition to high-definition white-light endoscopy could aid in the determination of residual dysplastic Barrett's esophagus after mucosal ablation or resection, the authors reported no additional benefit with pCLE [40].
Gastric cancer — Studies suggest a possible role for CLE in the evaluation of gastric cancer [41-45]. A classification scheme based upon pit patterns has been proposed to aid with the evaluation of gastric neoplasia [43].
●In a study of 27 patients, images were successfully obtained in 16 (59 percent). The CLE images from 52 examined sites were evaluated by two pathologists [41]. The sensitivity of CLE for gastric neoplasia was 82 to 91 percent, and the specificity was 98 percent. However, CLE failed to obtain adequate images in approximately 40 percent of the patients. Lesions at the fornix, antral lesser curvature, and the posterior wall of the gastric body were often difficult to image. This high failure rate for image acquisition may limit the value of CLE for detecting gastric neoplasia.
●In a second study, 521 sites from 137 patients were evaluated by CLE using a pit pattern classification that was developed based upon the examination of seven healthy controls and 10 resected gastric cancers [43]. Gastric cancer was present at 20 of the examined sites (4 percent) and was associated with a pit pattern characterized by the disappearance of the normal round pits and the appearance of diffusely atypical cells or glands. When that pattern was present, CLE had a sensitivity for detecting gastric cancer of 90 percent and a specificity of 99 percent. Interobserver and intraobserver variability were not reported.
●A third study included 1572 patients undergoing upper endoscopy with CLE [45]. The indications for the procedures included dyspeptic symptoms (the vast majority), gastric cancer, gastric polyps, gastritis, and suspicious lesions. Early gastric cancer was diagnosed in 40 patients on clinicopathologic grounds. An additional 15 patients had high-grade dysplasia. The sensitivity of CLE for detecting superficial neoplastic lesions (early gastric cancer or high-grade dysplasia) was 89 percent, and the specificity was 99 percent. The corresponding values for white-light endoscopy were 72 and 95 percent, respectively.
The accuracy of CLE diagnosing gastric lesion appears to be better than for Barrett's esophagus. Diagnostic accuracy has been reported to be greater than 90 percent in two studies that used either the eCLE [46] or pCLE system [44].
Colon polyps — Histologic architecture and microvascular changes are used to differentiate neoplastic polyps (eg, adenomas and carcinomas) from non-neoplastic polyps (eg, hyperplastic polyps). The following findings are seen with neoplasia [12,47]:
●Loss of goblet cells.
●Variable width of the epithelial layer with tubular-shaped (elongated) crypts.
●The lamina propria is thin and irregular.
●Due to the volume loss in the lamina propria, fewer blood vessels are present, which results in decreased diffusion of fluorescein and darkening of the image. In addition, the vessels may become irregular (tortuous with variable diameter) with leakage of fluorescein.
The clinical utility of CLE for colon polyps has been evaluated in several studies:
●One study looked at the ability of CLE to differentiate hyperplastic from adenomatous polyps [48]. A total of 37 polyps were evaluated in 25 patients. CLE discriminated between neoplastic and non-neoplastic polyps with a sensitivity of 83 percent and a specificity of 100 percent.
●A second report examined 162 colonic lesions as well as normal mucosal controls [49]. Chromoendoscopy was used to guide CLE (ie, lesions detected by chromoendoscopy were then further evaluated using CLE). Chromoendoscopy-guided CLE had a sensitivity of 97 percent and a specificity of 99 percent for predicting intraepithelial neoplasia. (See "Chromoendoscopy".)
●Another study with 102 lesions used a new classification for probe-based CLE. Presence of neoplasia was assessed by blinded scoring of video sequences. The overall accuracy (81 percent) for predicting neoplasia was acceptable but became excellent (94 percent) in cases where all blinded observers agreed [50].
Ulcerative colitis — Limited data suggest that CLE may be able to assess the degree of inflammation in patients with ulcerative colitis [51-53]. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Endoscopy and biopsy'.)
CLE was compared with routine surveillance colonoscopy in a report of 161 patients with chronic ulcerative colitis [52]. CLE detected significantly more areas of intraepithelial neoplasia (19 versus 4 with routine surveillance) and required fewer biopsies per patient (average 21 versus 42).
Bile duct strictures — CLE probes exist that are small enough to fit through the biopsy channel of a cholangioscope, making imaging of the hepatobiliary system possible. (See 'Confocal miniprobe' above.)
The goal is to differentiate benign from malignant strictures, which can be difficult. The diagnostic accuracy of other endoscopic methods (eg, brush cytology) is discussed elsewhere. (See "Endoscopic methods for the diagnosis of pancreatobiliary neoplasms", section on 'Brush cytology'.)
The available data on hepatobiliary CLE are promising [2,3,54-56]. The hallmarks of neoplasia in the bile duct include epithelial structures characterized by glands or villi and increased vascularity. The reported sensitivity of CLE for diagnosing neoplasia is 83 to 98 percent, and the specificity is 67 to 100 percent. In a study with 102 patients with indeterminate pancreaticobiliary strictures, 89 were able to be evaluated with CLE [54]. Forty patients were proven to have cancer. CLE had a sensitivity of 98 percent and a specificity of 67 percent for diagnosing malignancy.
In a second study with 14 patients, CLE was compared with standard histopathology [2]. CLE had a higher sensitivity than standard histopathology (83 versus 50 percent), but a lower specificity (88 versus 100 percent).
Cystic lesions of the pancreas — Cystic lesions of the pancreas are increasingly detected, most often by imaging modalities such as computed tomography scans. Evaluation of cystic lesions using miniprobe-based CLE introduced through a 19-gauge-needle (the needle used for fine-needle aspiration) during endoscopic ultrasound has been examined with increasing interest [57,58]. Preliminary data suggest that various morphologic features can be observed such as villous structures suggesting intraductal papillary mucinous neoplasia or a reticular pattern suggesting a serous cyst adenoma. It appears that needle-based CLE can help differentiate among different pancreatic cystic lesions (ie, mucinous cystic neoplasm, pseudocyst, or cystic neuroendocrine neoplasm) [59].
Diagnosis of food intolerance — CLE has been increasingly used for on-site diagnosis of food intolerance, such as allergy to wheat, soy, or yeast [60-62]. For this testing, diluted food antigens are administered to the intestinal mucosa with subsequent imaging. Possible reactions to food antigens include leakage of fluorescein, epithelial gaps, and increased blood flow, and these real-time responses have been considered as diagnostic features. In theory, such testing may improve the evaluation of suspected food intolerance. However, diagnostic criteria using CLE have not been standardized, and interobserver variability for this testing may be high.
Interobserver reliability — Many studies of CLE have demonstrated good interobserver agreement for the interpretation of the CLE images, with kappa values of 0.6 to 0.8 [31-33,35,63,64]. The kappa statistic is a measure of the agreement between two observers and can range from -1.0 to +1.0. If there is perfect agreement, the value is 1.0, whereas if the observed agreement is what would be expected by chance alone, the value is zero. If the degree of agreement is worse than what would be expected by chance, the kappa value will be negative, with complete disagreement resulting in a value of -1.0. Kappa statistics are often interpreted as:
●Excellent agreement – 0.8 to 1.0
●Good agreement – 0.6 to 0.8
●Moderate agreement – 0.4 to 0.6
●Fair agreement – 0.2 to 0.4
●Poor agreement – Less than 0.2
Although CLE is relatively easy to perform, there is a learning curve [65,66]. In one study, interobserver agreement was higher among gastroenterologists who had performed more than 30 CLE examinations compared with those who had performed fewer than 30 (kappa 0.72 versus 0.34).
Efficacy of endocytoscopy — Endocytoscopy has been studied for the evaluation of dysplasia and neoplasia in the esophagus, stomach, and colon. Other applications that have been described include visualization of Helicobacter pylori in the stomach [67] and real-time monitoring of blood flow in the rectal mucosa [68].
Squamous esophagus — The endocytoscopic findings of cancer include enlarged, irregularly arranged cell nuclei (picture 1). Endocytoscopy has a reported sensitivity of 80 to 90 percent for detecting neoplasia in the squamous esophagus [6,9]. Small studies have found the following:
●In a study of 25 patients, the overall sensitivity and specificity of endocytoscopy for diagnosing pathologic esophageal lesions were 81 and 100 percent, respectively [6]. When the x1100 magnification probe was used, the sensitivity and specificity were 91 and 100 percent, respectively; whereas, when the x450 magnification probe was used, they were 77 and 100 percent. However, the authors did not report whether the observed differences in sensitivity were statistically significant.
●In a second study of 28 patients who underwent endocytoscopy for lesions in the squamous esophagus, the sensitivity and specificity of endocytoscopy for detecting malignancy were 88 and 91 percent, respectively [9].
Stomach and columnar esophagus — Studies have reported variable accuracy of endocytoscopy for the detection of neoplasia arising from Barrett's esophagus or in the stomach [6,69,70]. The reason may be that topically applied contrast agents have difficulty penetrating the cells due to the thick mucin layers covering the epithelium. In addition, in the distal esophagus movement from respiration and esophageal contractions as well as difficult visual coupling may result in poor image resolution.
●In a report of 23 patients with gastric lesions, the sensitivity and specificity of endocytoscopy for predicting neoplastic change were 56 and 89 percent, respectively [6].
●In a study of 16 patients undergoing surveillance for Barrett's esophagus, attempts at obtaining adequate imaging were successful 51 percent of the time at x450 magnification and 22 percent of the time at x1125 magnification [69]. Of the images that could be assessed, the respective sensitivity and specificity for diagnosing dysplasia were 50 and 67 percent at x450 magnification and were 43 and 85 percent at x1125 magnification.
●In a study of 82 gastric lesions (23 early cancers, 10 adenomas, and 49 non-neoplastic lesions), 88 percent of the lesions could be evaluated by endocytoscopy [70]. A finding of high-grade atypia had a sensitivity of 86 percent and a specificity of 100 percent for diagnosing gastric cancer.
Colon — Endocytoscopically, adenomatous and malignant tissues in the colon are characterized by deformed, irregularly branching glands with enlarged cell nuclei and disordered cellular polarity. Preliminary studies of endocytoscopy for the evaluation of colon lesions have been promising:
●In one study with 75 lesions, the overall accuracy of endocytoscopy was 93 percent [8]. When it came to differentiating neoplastic from non-neoplastic lesions, the sensitivity and specificity were both 100 percent. In addition, of the 59 neoplastic lesions, 58 (98 percent) were correctly categorized as being either adenomas (46 lesions) or invasive cancers (12 lesions). One invasive cancer was misdiagnosed as an adenoma.
●In a second report that included 28 patients with colonic lesions, the sensitivity and specificity of endocytoscopy for diagnosing neoplasia were 79 and 90 percent, respectively [6].
●One study showed non-inferiority of endocytoscopy compared with standard histopathology for colorectal neoplasms. Overall, 101 lesions were available for primary outcome analysis. The diagnostic accuracy of endocytoscopy for the discrimination of neoplastic lesions was 94 percent, whereas that of standard biopsy was 96 percent [71].
●Endocytoscopy in combination with computer-aided diagnosis (CAD) has been used to identify histologic changes such as invasive colon cancer or mucosal inflammation [72,73]. For example, in a study evaluating 200 images of colonic lesions, the sensitivity and specificity of CAD-assisted endocytoscopy for diagnosing invasive cancer in colorectal polyps were 89.4 percent and 98.9 percent, respectively [73].
ADVERSE EVENTS — Adverse events related to the contrast agents used for confocal laser endomicroscopy and endocytoscopy have been reported. Problems with intravenous fluorescein are mainly due to its allergic properties.
In one study, no serious adverse events were reported in 2272 gastrointestinal procedures performed with intravenous fluorescein [74]. Mild adverse events occurred in 1.4 percent of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash, and mild epigastric pain.
Data are lacking on potential side effects for topical stains, such as methylene blue, crystal violet, cresyl violet, or acriflavine. However, some of these stains may cause DNA-damage and are therefore potentially mutagenic [75,76]. In addition, acriflavine and cresyl violet are not approved by the US Food and Drug Administration for use in humans.
SUMMARY AND RECOMMENDATIONS
●Background – Confocal laser endomicroscopy (CLE) and endocytoscopy are emerging endoscopic technologies that permit high-resolution assessment of gastrointestinal mucosal histology at a cellular and sub-cellular level. Endomicroscopy and endocytoscopy expand the imaging capabilities of flexible endoscopy by their ability to obtain "optical biopsies" of nearly any accessible endoluminal surface. (See 'Introduction' above.)
●Technical overview – CLE and endocytoscopy can be performed with probe-based systems that are passed through the working channel of an endoscope or with integrated endoscopic systems. For CLE, only probe-based systems are commercially available. (See 'Technical overview' above.)
●Clinical applications – The indications for confocal laser endomicroscopy (CLE) and endocytoscopy are still being defined. In general, CLE and endocytoscopy are used to target biopsies of abnormal tissue and to avoid taking biopsies of normal tissue. The goal is to increase diagnostic yield while minimizing procedure-related risks and the costs of tissue acquisition and analysis. (See 'Indications' above.)
Some applications of CLE and endocytoscopy include:
•Differentiation of neoplastic from non-neoplastic polyps and lesions (colon and stomach)
•Detection of neoplasia in patients with Barrett's esophagus or ulcerative colitis
•Differentiation of benign from malignant biliary strictures (probe-based CLE)
•Differentiation of cystic pancreatic lesions (probe-based CLE)
•Potentially detecting celiac disease
•Potentially detecting food allergies
While promising, available data on these techniques are sparse and further large-scale studies are needed to help define their roles. (See 'Efficacy' above.)
