The Accuracy of Confocal Laser Endomicroscopy in Diagnosing Bladder Cancer: A Systematic Review & Meta-Analyses

Background: Multiple advancements of endoscopic technology were designed to enhance the sensitivity and specificity of the diagnostic tools of bladder cancer; thus, we perform a meta-analysis to compare diagnostic performance between confocal laser endomicroscopy (CLE) and biopsy for detecting bladder cancer.Methods: We compared CLE’s accuracy in diagnosing bladder cancer reported by studies obtained from the electronic database MEDLINE, CENTRAL, and CINAHL, from May to June 2020. The pooled effect estimate was calculated employing the DerSimonian and Laird random-effects model. We only included moderate to high-quality studies, which had been assessed by the QUADAS-2 tool.Results: Eight studies were included in this review; five of those were good-quality studies. A total of 519 samples from 345 patients were included in the pooled effect estimate calculation. Pooled sensitivity and specificity of CLE in diagnosing bladder cancer were 90.2% (0.86, 0.93) and 78.1% (0.71, 0.85), respectively. The use of white-light cystoscopy (WLC) before CLE increased its specificity (56.8% versus 84.6%). Pooled sensitivity and specificity of CLE in predicting lowgrade lesion were 73% (0.66, 0.80) dan 83% (0.78, 0.87), respectively. Meanwhile, pooled sensitivity and specificity of CLE in predicting high-grade lesion were 73% (0.66, 0.78) and 79% (0.73, 0.83), respectively.Conclusions: CLE has good accuracy in distinguishing malignant and benign tumors. Grading tumors with this modality is also accurate. The use of probe CLE (pCLE), coupled with WLC, will increase its specificity.

Molecular Imaging of Ulex Europaeus Agglutinin in Colorectal Cancer Using Confocal Laser Endomicroscopy (With Video)

Background and Study AimsPrevious studies have identified that colorectal cancer has different fucosylation levels compared to the normal colon. Ulex europaeus agglutinin-I (UEA-I), which specifically combines with α1-2 fucose glycan, is usually used to detect fucosylation levels. Therefore, we used confocal laser endomicroscopy (CLE) to investigate fluorescently labeled UEA-Fluorescein isothiocyanate (FITC) for detecting colonic cancer.Patients and MethodsWe stained frozen mouse colon tissue sections of normal, adenoma, and adenocarcinoma species with UEA-FITC to detect fucosylation levels in different groups. White light endoscopy and endocytoscopy were first used to detect the lesions. The UEA-FITC was then stained in the mice and human colon tissues in vitro. The CLE was used to detect the UEA-FITC levels of the corresponding lesions, and videos were recorded for quantitation analysis. The diagnostic accuracy of UEA-FITC using CLE was evaluated in terms of sensitivity and specificity.ResultsThe UEA expression level in colorectal cancer was lower than that in normal intestinal epithelium. The fluorescence intensity ratio of UEA-FITC in colorectal cancer was significantly lower than that in normal tissue detected by CLE in both mice and humans. The combination of UEA-FITC and CLE presented a good diagnostic accuracy with a sensitivity of 95.6% and a specificity of 97.7% for detecting colorectal cancer. The positive and negative predictive values were 91.6% and 95.6%, respectively. Overall, 95.6% of the sites were correctly classified by CLE.ConclusionsWe developed a new imaging strategy to improve the diagnostic efficacy of CLE by using UEA-FITC.

Effects of Fluid Therapy on Mesenteric Microcirculation Using New Probe-Based Confocal Laser Endomicroscopy (Cellvizio®) in a Porcine Model of Endotoxic Shock

<b><i>Background:</i></b> Microcirculatory alterations have been observed at the early phase of sepsis, although macrocirculation seems preserved. The aim of this study was to analyze the effect of crystalloid fluid therapy on mesenteric microcirculation, assessed by using the confocal laser endomicroscope Cellvizio®, in an endotoxic porcine model. <b><i>Methods:</i></b> It is a prospective endotoxic shock (lipopolysaccharide infusion) experimental trial. Piglets were divided into 3 groups: 6 in the sham group (no LPS injection, no fluid), 9 in the control group (LPS infusion, no fluid), and 6 in the crystalloids group (LPS infusion and fluid resuscitation with crystalloids). Fluid resuscitation consisted in a fluid bolus of 20 mL/kg 0.9% saline over 30 min followed by a 10 mL/kg/h fluid rate over 4 h. Mesenteric microcirculation was assessed using a confocal laser endomicroscope (Cellvizio®). Blood flow within capillaries was visually assessed according to the point of care microcirculation (POEM) score. <b><i>Results:</i></b> At baseline, the 3 groups were similar regarding hemodynamic, biological, and microcirculatory parameters. At T360, the POEM score significantly decreased in the control and crystalloids groups, whereas it remained unchanged in the sham group (respectively, 1.62 ± 1.06, 1.2 ± 0.45, and 5.0 ± 0, <i>p</i> = 0.011). There was no significant difference in cardiac output at T360 between the sham and crystalloids groups (3.1 ± 0.8 vs. 2.3 ± 0.6, <i>p</i> = 0.132) or between the control and crystalloids groups (2.0 ± 0.6 vs. 2.3 ± 0.6, <i>p</i> = 0.90). <b><i>Conclusion:</i></b> There was no significant improvement of microcirculatory alterations after crystalloids resuscitation despite improvement in macrocirculatory parameters in early experimental sepsis.

Diagnostic Accuracy of Confocal Laser Endomicroscopy for the Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Background: Advances in treatment approaches for patients with oral squamous cell carcinoma (OSCC) have been unsuccessful in preventing frequent recurrences and distant metastases, leading to a poor prognosis. Early detection and prevention enable an improved 5-year survival and better prognosis. Confocal Laser Endomicroscopy (CLE) is a non-invasive imaging instrument that could enable an earlier diagnosis and possibly help in reducing unnecessary invasive surgical procedures. Objective: To present an up to date systematic review and meta-analysis assessing the diagnostic accuracy of CLE in diagnosing OSCC. Materials and Methods. PubMed, Scopus, and Web of Science databases were explored up to 30 June 2021, to collect articles concerning the diagnosis of OSCC through CLE. Screening: data extraction and appraisal was done by two reviewers. The quality of the methodology followed by the studies included in this review was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random effects model was used for the meta-analysis. Results: Six studies were included, leading to a total number of 361 lesions in 213 patients. The pooled sensitivity and specificity were 95% (95% CI, 92–97%; I2 = 77.5%) and 93% (95% CI, 90–95%; I2 = 68.6%); the pooled positive likelihood ratios and negative likelihood ratios were 10.85 (95% CI, 5.4–21.7; I2 = 55.9%) and 0.08 (95% CI, 0.03–0.2; I2 = 83.5%); and the pooled diagnostic odds ratio was 174.45 (95% CI, 34.51–881.69; I2 = 73.6%). Although risk of bias and heterogeneity is observed, this study validates that CLE may have a noteworthy clinical influence on the diagnosis of OSCC, through its high sensitivity and specificity. Conclusions: This review indicates an exceptionally high sensitivity and specificity of CLE for diagnosing OSCC. Whilst it is a promising diagnostic instrument, the limited number of existing studies and potential risk of bias of included studies does not allow us to draw firm conclusions. A conclusive inference can be drawn when more studies, possibly with homogeneous methodological approach, are performed.

Socio-Organizational Impact of Confocal Laser Endomicroscopy in Neurosurgery and Neuropathology: Results from a Process Analysis and Expert Survey

During brain tumor resection surgery, it is essential to determine the tumor borders as the extent of resection is important for post-operative patient survival. The current process of removing a tissue sample for frozen section analysis has several shortcomings that might be overcome by confocal laser endomicroscopy (CLE). CLE is a promising new technology enabling the digital in vivo visualization of tissue structures in near real-time. Research on the socio-organizational impact of introducing this new methodology to routine care in neurosurgery and neuropathology is scarce. We analyzed a potential clinical workflow employing CLE by comparing it to the current process. Additionally, a small expert survey was conducted to collect data on the opinion of clinical staff working with CLE. While CLE can contribute to a workload reduction for neuropathologists and enable a shorter process and a more efficient use of resources, the effort for neurosurgeons and surgery assistants might increase. Experts agree that CLE offers huge potential for better diagnosis and therapy but also see challenges, especially due to the current state of experimental use, including a risk for misinterpretations and the need for special training. Future studies will show whether CLE can become part of routine care.

Technical Note: First Use of Endonasal Confocal Laser Endomicroscopy – Feasibility and Proof of Concept

Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses.Further investigation and validation will be necessary.

Modern technologies of diagnosis and treatment of patient with alveolar proteinosis

The case of a rare lung disease - alveolar proteinosis diagnosed with advanced technologies, including confocal laser endomicroscopy of respiratory tract (alveoscopy) is presented. After confirming the diagnosis the patient undewent high volume bronchoalveolar lavage of both lungs with positive clinical and radiologic dynamics.