Diffuse low-grade gliomas are infiltrative tumors whose margins are not distinguishable from the adjacent healthy brain parenchyma. The aim was to precisely examine the results provided by the intraoperative use of macroscopic fluorescence in diffuse low-grade gliomas and to describe the new fluorescence-based techniques capable of guiding the resection of low-grade gliomas. Only about 20% and 50% of low-grade gliomas are macroscopically fluorescent after 5-amino-levulinic acid (5-ALA) or fluorescein sodium intake, respectively. However, 5-ALA is helpful for detecting anaplastic foci, and thus choosing the best biopsy targets in diffuse gliomas. Spectroscopic detection of 5-ALA-induced fluorescence can detect very low and non-macroscopically visible concentrations of protoporphyrin IX, a 5-ALA metabolite, and, consequently, has excellent performances for the detection of low-grade gliomas. Moreover, these tumors have a specific spectroscopic signature with two fluorescence emission peaks, which is useful for distinguishing them not only from healthy brain but also from high-grade gliomas. Confocal laser endomicroscopy can generate intraoperative optic biopsies, but its sensitivity remains limited. In the future, the coupled measurement of autofluorescence and induced fluorescence, and the introduction of fluorescence detection technologies providing a wider field of view could result in the development of operator-friendly tools implementable in the operative routine.

OBJECTIVE: Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined.
METHODS: We searched PubMed using keywords (\"confocal\" OR \"CLE\" OR \"endocytoscopy\") AND (\"IBD\" OR \"inflammatory bowel\" OR \"Crohn*\" OR \"Crohn\'s\" OR \"colitis ulcerosa\" OR \"ulcerative colitis\") between 2005 and March 2023. We identified 52 studies for detailed review.
RESULTS: Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn\'s disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC. EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study.
CONCLUSIONS: Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Pediatric endoscopy has revolutionized the way we diagnose and treat gastrointestinal disorders in children. Technological advances in computer processing and imaging continue to affect endoscopic equipment and advance diagnostic tools for pediatric endoscopy. Although commonly used by adult gastroenterologists, modalities, such as endomicroscopy, image-enhanced endoscopy, and impedance planimetry, are not routinely used in pediatric gastroenterology. This state-of-the-art review describes advances in diagnostic modalities, including image-enhanced endoscopy, confocal laser endomicroscopy, optical coherence tomography, endo functional luminal imaging probes, wireless motility/pH capsule, wireless colon capsule endoscopy, endoscopic ultrasound, and discusses the basic principles of each technology, including adult indications and pediatric applications, safety cost, and training data.

Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC.

When we talk about visualization methods in surgery, it is important to mention that the diagnosis of tumors and how we define tumor borders intraoperatively in a correct way are two main things that would not be possible to achieve without this grand variety of visualization methods we have at our disposal nowadays. In addition, histopathology also plays a very important role, and its importance cannot be neglected either. Some biopsy specimens, e.g., frozen sections, are examined by a histopathologist and lead to tumor diagnosis and the definition of its borders. Furthermore, surgical resection is a very important point when it comes to prognosis and life survival. Confocal laser endomicroscopy (CLE) is an imaging technique that provides microscopic information on the tissue in real time. CLE of disorders, such as head, neck and brain tumors, has only recently been suggested to contribute to both immediate tumor characterization and detection. It can be used as an additional tool for surgical biopsies during biopsy or surgical procedures and for inspection of resection margins during surgery. In this review, we analyze the development, implementation, advantages and disadvantages as well as the future directions of this technique in neurosurgical and otorhinolaryngological disciplines.

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.
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.

Chronic pancreatitis (CP) is a progressive condition caused by several factors and characterised by pancreatic fibrosis and dysfunction. However, CP is difficult to diagnose at an early stage. Various advanced methods including endoscopic ultrasound based elastography and confocal laser endomicroscopy have been used to diagnose early CP, although no unified diagnostic standards have been established. In the past, the diagnosis was mainly based on imaging, and no comprehensive evaluations were performed. This review describes and compares the advantages and limitations of the traditional and latest diagnostic modalities and suggests guidelines for the standardisation of the methods used to diagnose early CP.

The diagnostic process for biliary strictures remains challenging in some cases. A broad differential diagnosis exists for indeterminate biliary strictures, including benign or malignant lesions. The diagnosis of indeterminate biliary strictures requires a combination of physical examination, laboratory testing, imaging modalities, and endoscopic procedures. Despite the progress of less invasive imaging modalities such as transabdominal ultrasonography, computed tomography, and magnetic resonance imaging, endoscopy plays an essential role in the accurate diagnosis, including the histological diagnosis. Imaging findings and brush cytology and/or forceps biopsy under fluoroscopic guidance with endoscopic retrograde cholangiopancreatography (ERCP) are widely used as the gold standard for the diagnosis of biliary strictures. However, ERCP cannot provide an intraluminal view of the biliary lesion, and its outcomes are not satisfactory. Recently, peroral cholangioscopy, confocal laser endomicroscopy, endoscopic ultrasound (EUS), and EUS-guided fine-needle aspiration have been reported as useful for indeterminate biliary strictures. Appropriate endoscopic modalities need to be selected according to the patient\'s condition, the lesion, and the expertise of the endoscopist. The aim of this review article is to discuss the diagnostic process for indeterminate biliary strictures using endoscopy.

OBJECTIVE: To systematically evaluate the diagnostic efficacy of confocal laser endomicroscopy (CLE) in detection of bladder cancer.
METHODS: A systematic literature search on CLE in diagnosing bladder cancer in PubMed, Embase, and the Cochrane Library databases was performed. A bivariate meta-regression model was used for meta-analysis to evaluate the pooled diagnostic value of CLE.
RESULTS: A total of 5 eligible studies involving 302 lesions were available for this meta-analysis. In a per-lesion analysis, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver-operating curve (SROC) area under the curve (AUC) of CLE for malignant lesions were 0.90 (95% confidence interval [CI]: 0.85-0.94), 0.72 (95% CI: 0.59-0.82), 3.20 (95% CI: 2.14-4.79), 0.14 (95% CI: 0.09-0.21), 23.27 (95% CI: 11.71-46.25), and 0.91 (95% CI: 0.89-0.94), respectively. For low-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.72 (95% CI: 0.57-0.84), 0.87 (95% CI: 0.77-0.93), 5.48 (95% CI: 3.12-9.62), 0.32 (95% CI: 0.20-0.50), 17.19 (95% CI: 8.01-36.89), and 0.85 (95% CI: 0.82-0.88), respectively. For high-grade urothelial carcinomas, pooled sensitivity, specificity, PLR, NLR, DOR, and AUC for CLE were 0.82 (95% CI: 0.62-0.92), 0.84 (95% CI: 0.73-0.91), 4.96 (95% CI: 2.58-9.54), 0.22 (95% CI: 0.09-0.52), 22.49 (95% CI: 5.33-94.85), and 0.89 (95% CI: 0.86-0.91), respectively.
CONCLUSIONS: CLE is a promising endoscopy technique for real-time tumor grading of bladder cancer.

Endomicroscopy is an emerging imaging modality, that facilitates the acquisition of in vivo, in situ optical biopsies, assisting diagnostic and potentially therapeutic interventions. While there is a diverse and constantly expanding range of commercial and experimental optical biopsy platforms available, fibre-bundle endomicroscopy is currently the most widely used platform and is approved for clinical use in a range of clinical indications. Miniaturised, flexible fibre-bundles, guided through the working channel of endoscopes, needles and catheters, enable high-resolution imaging across a variety of organ systems. Yet, the nature of image acquisition though a fibre-bundle gives rise to several inherent characteristics and limitations necessitating novel and effective image pre- and post-processing algorithms, ranging from image formation, enhancement and mosaicing to pathology detection and quantification. This paper introduces the underlying technology and most prevalent clinical applications of fibre-bundle endomicroscopy, and provides a comprehensive, up-to-date, review of relevant image reconstruction, analysis and understanding/inference methodologies. Furthermore, current limitations as well as future challenges and opportunities in fibre-bundle endomicroscopy computing are identified and discussed.