Search Results (92)

Background: Brain metastases are the most common intracranial tumors in adults and are traditionally considered well-demarcated lesions amenable to complete surgical resection. Nonetheless, increasing histopathological evidence demonstrates that metastatic cells may infiltrate beyond the contrast-enhancing margin into surrounding brain parenchyma, challenging the reliability of conventional imaging for defining true tumor boundaries. Confocal laser endomicroscopy (CLE) using Sodium Fluorescein (SF) has emerged as a novel intraoperative imaging modality capable of providing real-time, high-resolution optical biopsies, potentially improving margin assessment during metastasis surgery. Methods: A systematic literature search was performed according to PRISMA guidelines across PubMed, Embase, Scopus, Cochrane Library, and Google Scholar up to 3 March 2026. Studies evaluating intraoperative CLE with SF in adult patients with brain metastases were included. Data regarding study design, patient population, CLE system, imaging characteristics, and diagnostic performance were extracted. Risk of bias was assessed using the QUADAS-2 tool. Results: Ten studies met the inclusion criteria for qualitative synthesis, comprising over 650 patients; however, most studies included heterogeneous intracranial tumor populations, with only a subset specifically involving brain metastases. CLE enabled real-time visualization of tumor microarchitecture and demonstrated high sensitivity for tumor detection, frequently exceeding 90% in prospective studies. Specificity varied across studies, reflecting challenges in distinguishing tumor infiltration from reactive tissue at the tumor–brain interface. The MetInfilt trial highlighted that infiltrative growth patterns are common in brain metastases and can be visualized intraoperatively using CLE. Additional studies demonstrated that fluorescein-based CLE allows differentiation of tumor zones and may facilitate targeted margin assessment; however, evidence demonstrating improvement in clinically meaningful outcomes such as extent of resection, local recurrence, progression-free survival, or overall survival remains limited. Conclusions: Confocal laser endomicroscopy using SF represents a promising intraoperative adjunct for assessing tumor margins in brain metastasis surgery. By enabling real-time microscopic visualization of the metastasis–brain interface, CLE may support a more biologically informed surgical strategy. Full article

In this review, we explore the evolving role of endoscopic ultrasound (EUS) in diagnosing and managing pancretobiliary malignancies. For solid pancreatic lesions, techniques like fine-needle biopsy (FNB), contrast-enhanced EUS (CE-EUS), and macroscopic on-site evaluation (MOSE) improve sample quality and diagnostic accuracy. In cystic pancreatic lesions, fine-needle aspiration (FNA), molecular testing, and confocal laser endomicroscopy (nCLE) aid in distinguishing benign from malignant cysts. For cholangiocarcinoma, EUS guided sampling is more accurate than CT in assessing distal lesions and lymph node metastases, while combining EUS with magnetic resonance cholangiography (MRC) enhances diagnostic sensitivity. In gallbladder cancer, EUS surpasses CT and MRI in detecting lymphadenopathy and staging tumors. EUS-FNB (Fine needle biopsy) improves biopsy accuracy, especially for unresectable cases. These advancements highlight EUS as a critical tool for early cancer detection, staging, and tissue acquisition. Beyond diagnosis, EUS plays a pivotal therapeutic role in managing complications such as malignant biliary obstruction and gastric outlet obstruction, offering minimally invasive alternatives like EUS-guided biliary drainage and gastroenterostomy with high clinical success and improved patient outcomes. Full article

The endoscopic findings of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are highly nonspecific and the sampling error or false-negative probabilities during conventional biopsy make its diagnosis more challenging. Confocal laser endomicroscopy is a novel technology which allows in vivo microscopic analysis of gastrointestinal mucosa. Here we present a case of gastric MALT lymphoma by targeted biopsy guided by magnifying endoscopy and probe-based confocal laser endomicroscopy. Full article

Background/Objectives: We developed a telehealth-enabled fiber-bundle endomicroscopy platform and evaluated its preclinical feasibility for targeted fluorescence imaging in cervical cancer models. Methods: The platform integrates a portable fiber-bundle endomicroscopy (FBE) system, fluorescein isothiocyanate (FITC)-labeled candidate peptides, and a secure web-based telehealth platform for remote consultation. The FBE probe achieved a field of view of 1,700 µm and a lateral resolution of 4 µm, enabling cellular-level fluorescence imaging in a compact, portable format. Four FITC-labeled peptides (SHS1*, SHS2*, FPP*, and CRL*) were evaluated in A549, SiHa, and CaSki cell lines. Ex vivo testing was performed on commercial cervical tissue-array samples. The telehealth platform was assessed for secure medical-image/video transmission and end-to-end latency in a simulated remote-consultation setting. Results: Among the tested probes, FPP*-FITC and CRL*-FITC showed higher fluorescence-positive fractions in the p16-overexpressing cervical cancer cell lines than in the A549 comparator line, with the strongest signals observed in CaSki cells. In ex vivo testing, CRL*-FITC generated higher fluorescence intensity in malignant cervical tissue-array samples than in non-malignant comparator tissues, with a reported 4.6- to 7.4-fold difference in mean signal intensity (p < 0.001). The telehealth platform supported the secure transmission of medical images and video and demonstrated an end-to-end latency of <500 ms in a simulated remote consultation setting. Conclusions: These results support the technical and preclinical feasibility of integrating targeted fluorescence imaging, portable fiber-bundle endomicroscopy, and telehealth into a single platform. This study should therefore be interpreted as a preclinical feasibility study evaluating optical, molecular, and telehealth integration, rather than as a clinically validated cervical cancer screening test. Full article

Glioblastoma (GBM) remains the most aggressive primary malignant brain tumor in adults, with poor survival largely driven by diffuse cellular infiltration, profound heterogeneity, and near-universal recurrence following standard therapy. Although maximizing the extent of resection is a key determinant of patient outcome, current clinical imaging modalities lack the spatial resolution necessary to detect microscopic tumor invasion and therapy-resistant cell populations. Emerging in vivo imaging technologies capable of cellular and near-single-cell resolution have therefore become a major focus in preclinical neuro-oncology research, with growing relevance for surgical guidance, treatment adaptation, and translational discovery. This review evaluates multiple optical imaging modalities, including multi-photon microscopy, near-infrared II fluorescence imaging, bioluminescence imaging, photoacoustic imaging, optical coherence tomography, confocal laser endomicroscopy, Raman spectroscopy, autofluorescence microscopy, and fluorescence macroscopy with a focus on their ability to detect residual GBM cells. Despite significant advances, these approaches remain constrained by limitations in molecular target availability, probe delivery across the blood–brain barrier, and signal variability within heterogeneous tumor regions. The biological complexity of GBM further challenges detection, as residual tumor cells are spatially dispersed and phenotypically diverse, limiting the effectiveness of single-marker or single-modality strategies. Together, these findings highlight the need for integrated, biologically informed imaging approaches to improve detection of residual disease and guide surgical decision making. Full article

Background: Endoscopic assessment is central to the management of inflammatory bowel disease (IBD), particularly within treat-to-target strategies. However, conventional high-definition white-light endoscopy (HD-WLE) is limited by interobserver variability and its inability to reliably reflect microscopic inflammation or predict long-term outcomes. Over the last decade, multiple technological innovations have reshaped the role of endoscopy in both disease activity monitoring and dysplasia surveillance. Methods: This narrative review provides a comprehensive and clinically oriented overview of emerging endoscopic technologies in IBD, including image-enhanced endoscopy, ultra-high-magnification techniques, artificial intelligence (AI), and molecular imaging. We discuss their diagnostic performance, prognostic implications, and potential integration into clinical practice. Results: Image-enhanced endoscopy improves visualization of subtle mucosal and vascular alterations and demonstrates stronger correlation with histological activity compared with HD-WLE alone. Confocal laser endomicroscopy and endocytoscopy enable in vivo microscopic assessment of epithelial architecture and barrier integrity, redefining remission beyond macroscopic healing. AI systems have shown expert-level performance in grading inflammatory severity in ulcerative colitis and high sensitivity in capsule endoscopy for Crohn’s disease, supporting objective and reproducible assessment. In surveillance, targeted high-definition inspection has replaced random biopsies, while adjunctive optical and AI-based tools enhance lesion detection and characterization. Molecular imaging introduces a predictive dimension by enabling visualization of drug–target engagement and dysplasia-specific pathways. Conclusions: Endoscopy in IBD is evolving from a descriptive modality toward a multimodal precision tool integrating enhanced imaging, AI-driven standardization, and molecular profiling. Although further validation and cost-effectiveness studies are required, these innovations have the potential to improve therapeutic stratification, surveillance strategies, and long-term patient outcomes. Full article

Pancreatic cystic lesions (PCLs) include clinically challenging conditions that range from benign to malignant prognoses. Their prevalence is increasing, and they are often detected as incidental findings during cross-sectional imaging. Thus, endoscopic ultrasound (EUS) plays a pivotal role in investigating these lesions. In this review, we analyze the complete diagnostic potential of EUS. Contrast-enhanced EUS, contrast-harmonic EUS, and elastography are useful for distinguishing between benign and malignant forms, and detective flow imaging EUS and e-FLOW EUS have enhanced the diagnostic arsenal available. Fine-needle aspiration (FNA) is important for obtaining cystic fluid for biochemical analysis and cytological examinations. Confocal laser endomicroscopy and through-the-needle biopsy represent adjunctive techniques for refined and difficult diagnosis. Moreover, artificial intelligence could be a promising modality in the EUS world. EUS allows PCLs to be detected accurately and plays a relevant role in identifying malignant forms. Full article

Confocal laser endomicroscopy (CLE) is an innovative diagnostic modality that facilitates real-time in vivo optical biopsies of various tissues within luminal and ductal structures. Since its introduction in 2004, the application of this tool has broadened from diagnostic purposes to encompass management and prognostic evaluation in fields such as gastroenterology, neurosurgery, urology, and dermatology. This comprehensive review examines the current applications of endomicroscopy in Barrett’s esophagus (BE), inflammatory bowel disease (IBD), and colorectal lesions. Evidence from the literature suggests that CLE offers a potential solution to the diagnostic limitations associated with white-light endoscopy and histology. With a diagnostic accuracy nearly equivalent to that of histology, CLE is emerging as a promising tool to mitigate the delays related to awaiting histology results for clinical and therapeutic decision-making. However, its use is mainly as a complementary diagnostic method rather than an alternative to histopathology or other ancillary studies. Nevertheless, its widespread adoption remains limited, and further research is necessary to ascertain its overall benefits and cost implications of integrating it into patient care. Full article

Multiphoton endomicroscopy (MPEM) has recently become a key development in optical biomedical diagnostics, providing histologically relevant in vivo images that are eliminating both the need for tissue damage during biopsy sampling and the need for dye injections. Due to its ability to visualize structures at the epithelial, extracellular matrix, and subcellular levels, MPEM offers a promising diagnostic method for precancerous conditions and early forms of gastrointestinal (GI) cancer. The high specificity of multiphoton signals—the two-photon fluorescence response of endogenous fluorophores (NADH, FAD), the second-harmonic generation signal from collagen, and others—makes this method a promising alternative to both traditional histology and confocal endoscopy, enabling real-time assessment of metabolic status, intestinal epithelial cell status, and stromal remodeling. Despite the promising prospects of multiphoton microscopy, its practical implementation is progressing extremely slowly. The main factors here include the difficulty of delivering ultrashort pulses with high peak power, which is necessary for multiphoton excitation (MPE), and obtaining these pulses at the required wavelengths to activate the autofluorescence mechanism. One of the most promising solutions is the use of specialized multimode optical fibers that can both induce beam self-cleaning (BSC), which allows for the formation of a stable beam profile close to the fundamental mode, and significantly broaden the optical spectrum, which can ultimately cover the entire region of interest. This review presents the biophysical foundations of multiphoton microscopy of GI tissue, existing endoscopic architectures for MPE, and an analysis of the potential for using novel nonlinear effects in multimode optical fibers, such as the BSC effect and supercontinuum generation. It is concluded that the use of optical fibers in which the listed effects are realized in the tracts of multiphoton endomicroscopes can become a key step in the creation of a new generation of high-resolution instruments for the early detection of malignant neoplasms of the GI tract. Full article

Celiac disease (CeD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals, with a heterogeneous clinical spectrum spanning classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical forms. We synthesize contemporary epidemiology, immunopathogenesis, and the updated 2025 European Society for the Study of Coeliac Disease diagnostic framework. Adaptive responses to deamidated gliadin peptides presented by human leukocyte antigen (HLA)-DQ2/DQ8, together with interleukin-15-driven activation of intraepithelial lymphocytes (IELs), culminate in villous atrophy, crypt hyperplasia, and increased IELs. Serology centered on tissue transglutaminase immunoglobulin A (tTG-IgA) with total immunoglobulin A assessment remains first-line, complemented by standardized duodenal sampling (≥4 distal + 2 bulb biopsies) and selective HLA typing. The guidelines conditionally endorse a no-biopsy pathway for adults <45 years with tTG-IgA ≥10× upper limit of normal confirmed on a second sample, emphasizing shared decision-making and exclusion of red flags. We delineate differential diagnoses (tropical sprue, Crohn’s disease, common variable immunodeficiency, small intestinal bacterial overgrowth) and contrast CeD with non-celiac gluten sensitivity, which lacks villous atrophy, disease-specific serology, and HLA association. Emerging tools (immunohistochemistry, CD3/CD8/γδ IELs, video capsule endoscopy, confocal laser endomicroscopy) and the limitations of salivary/fecal assays are reviewed. Early detection improves quality of life and reduces healthcare utilization. Future directions include artificial intelligence-assisted imaging, molecular immunophenotyping, and non-dietary therapeutics. Full article

Optical imaging technologies expand gastrointestinal endoscopy beyond white-light endoscopy (WLE), improving visualization of mucosal, vascular, and subsurface features. They are applied to the detection of neoplastic and premalignant lesions, inflammatory diseases, and small bowel and pancreatic disorders, though their validation and readiness for routine practice vary. This review critically evaluates both guideline-endorsed and investigational optical imaging techniques across major gastrointestinal indications, highlighting diagnostic performance, level of validation, current guideline recommendations, and practical challenges to adoption. In Barrett’s esophagus, narrow-band imaging (NBI) is guideline-endorsed, while acetic acid chromoendoscopy is validated in expert centers. For gastric intestinal metaplasia and early gastric cancer, magnifying NBI achieves diagnostic accuracies exceeding 90% and is guideline-recommended, with acetic acid chromoendoscopy aiding in margin delineation. In inflammatory bowel disease, dye-spray chromoendoscopy is the reference standard for dysplasia surveillance, with virtual methods such as NBI, FICE, and i-SCAN serving as practical alternatives when dye application is not feasible. In the colorectum, NBI supports validated optical diagnosis strategies (resect-and-discard, diagnose-and-leave), while dye-based chromoendoscopy improves detection of flat and serrated lesions. Capsule endoscopy remains the standard for small bowel evaluation of bleeding, Crohn’s disease, and tumors, with virtual enhancement, intelligent chromo capsule endoscopy, and AI-assisted interpretation emerging as promising adjuncts. Pancreaticobiliary applications of optical imaging are also advancing, though current evidence is still preliminary. Investigational modalities including confocal laser endomicroscopy, optical coherence tomography, autofluorescence, Raman spectroscopy, and fluorescence molecular imaging show potential but remain largely restricted to research or expert settings. Guideline-backed modalities such as NBI and dye-based chromoendoscopy are established for clinical practice and supported by robust evidence, whereas advanced techniques remain investigational. Future directions will rely on broader validation, integration of artificial intelligence, and adoption of molecularly targeted probes and next-generation capsule technologies, which together may enhance accuracy, efficiency, and standardization in gastrointestinal endoscopy. Full article

Early diagnosis of pancreatic cancer, particularly in intraductal papillary mucinous neoplasm (IPMN), remains challenging despite advances in imaging and biomarkers. Pancreatic adenocarcinoma (PDAC) has a high mortality rate; therefore, its early detection and adequate interventions are necessary to improve the disease outcome. Most IPMNs are asymptomatic and discovered incidentally. Magnetic resonance imaging (MRI) is a preferred tool for diagnosing malignant IPMNs, with a sensitivity of 90.7–94.1% and a specificity of 84.7–87.2% in detecting mural nodules > 5 mm, a strong predictor of high-risk lesions. Radiomics further enhances diagnostic accuracy (sensitivity 91–96%, specificity 78–81%), especially when combined with CA 19-9, which has lower sensitivity (73–90%) but higher specificity (79–95%). Computed tomography (CT), though less effective for small mural nodules, remains widely used; its accuracy improves with radiomics and clinical variables (sensitivity 90.4%, specificity 74%). Conventional endoscopic ultrasonography (EUS) shows lower performance (sensitivity 60%, specificity 80%), but its advanced variations have improved outcomes. Contrast-enhanced EUS (CE-EUS) visualizes mural nodules with more than 90% sensitivity and involvement of the main pancreatic duct, with a sensitivity of 83.5% and a specificity of 87%. EUS–fine-needle aspiration (EUS-FNA) allows cyst fluid analysis; however, CEA, glucose, and KRAS/GNAS mutations show poor value for malignancy risk. Cytology has low sensitivity (28.7–64.8%) but high specificity (84–94%) in diagnostic malignant changes and strongly affects further management. EUS–through-the-needle biopsy (EUS-TTNB) yields high diagnostic accuracy (sensitivity 90%, specificity 95%) but carries a range of 2–23% adverse events, which limits its wide use. EUS–confocal laser endomicroscopy (EUS-nCLE) provides real-time microscopic evaluation, detecting malignant IPMN with a sensitivity of 90% and a specificity of 73%, though its availability is limited. New emerging biomarkers available in cyst fluid or blood include mucins, miRNA panels (sensitivity 66.7–89%, specificity 89.7–100%), lipidomics, and cancer metabolite profiling, with diagnostic accuracy approaching 89–91%. Pancreatoscopy (POP) enables direct main pancreatic duct (MPD) visualization and biopsy with a sensitivity of 64–100% and a specificity of 75–100%, though adverse events occur in around 12% cases. Combining advanced imaging, EUS-based tissue acquisition, and novel biomarkers holds promise for earlier and more accurate detection of malignant IPMN, potentially improving PDAC outcomes. Full article

Introduction: Artificial intelligence (AI) is increasingly being applied to improve the diagnosis and management of inflammatory bowel disease (IBD). Aims and Methods: We conducted a narrative review of the literature on AI applications in IBD endoscopy, focusing on diagnosis, disease activity assessment, therapy prediction, and detection of dysplasia. Results: AI systems have demonstrated high accuracy in assessing endoscopic and histological disease activity in ulcerative colitis and Crohn’s disease, with performance comparable to expert clinicians. Machine learning models can predict response to biologics and risk of complications. AI-assisted technologies like confocal laser endomicroscopy enable real-time histological assessment. Computer-aided detection systems improve identification of dysplastic lesions during surveillance. Challenges remain, including need for larger datasets, external validation, and addressing potential biases. Conclusions: AI has significant potential to enhance IBD care by providing rapid, objective assessments of disease activity, predicting outcomes, and assisting in dysplasia surveillance. However, further validation in diverse populations and prospective studies are needed before widespread clinical implementation. With ongoing advances, AI is poised to become a valuable tool to support clinical decision-making and improve patient outcomes in IBD. Addressing methodological, regulatory, and cost barriers will be crucial for the successful integration of AI into routine IBD management. Full article

Gastrointestinal graft-versus-host disease (GvHD) is a frequent and severe complication after allogeneic stem cell transplantation (aSCTx). Although biopsy and histopathology remain the gold standard for diagnosis of GvHD, this approach can be limited by thrombocytopenia accompanying aSCTx and the diagnostic delay associated with routine histopathology. Here, we report on two patients in which dye-based contact microscopy using a latest generation endocytoscope with 520-fold magnification enabled in vivo diagnosis of GvHD. The first patient was a 23-year-old man with acute lymphoblastic leukemia presenting with non-bloody diarrhea 3 months after aSCTx. After topical staining with crystal violet and methylene blue, endocytoscopy in the rectum showed several apoptotic epithelial cells. Histopathology confirmed GvHD grade III according to the Lerner classification. The second patient was a 59-year-old female with diarrhea 3 months after aSCTx. Apart from pathognomic apoptotic bodies, EC additionally revealed crypt lumina enlargement and mononuclear cell infiltrates in the lamina propria with subsequent crypt distension. The duration of the procedure was less than 5 min in each patient. These findings illustrate that in vivo microscopy using endocytoscopy can enable instantaneous diagnosis of GvHD with the benefit of accelerating therapeutic decisions in patients with suspected severe GvHD. Full article

In prostate cancer (PCa) surgery, precise tumor margin identification remains challenging despite advances in surgical techniques. This study evaluates the combination of tumor-specific near-infrared imaging with the PSMA-targeting molecule PSMA-914 and optical endomicroscopy (NIR-pCLE) for single-cell-level tumor identification in a preclinical proof of concept. Methods: NIR-pCLE imaging of varying PSMA-914 concentrations was performed on PSMA-positive LNCaP and PSMA-negative PC-3 cells using Cellvizio^® 100 with pCLE Confocal Miniprobes™. To identify optimal PSMA-914 dosing for in vivo imaging, different doses (0–10 nmol) were evaluated using NIR-pCLE, Odyssey CLx imaging, and confocal microscopy in an LNCaP tumor-bearing xenograft model. A proof of concept mimicking a clinical workflow was performed using 5 nmol [⁶⁸Ga]Ga-PSMA-914 in LNCaP and PC-3 tumor xenografts, including PET/MRI, in/ex vivo NIR-pCLE imaging, and microscopic/macroscopic imaging. Results: NIR-pCLE detected PSMA-specific fluorescence at concentrations above 30 nM in vitro. The optimal dose was identified as 5 nmol PSMA-914 for NIR-pCLE imaging with cellular resolution in LNCaP xenografts. PET/MRI confirmed high tumor uptake and a favorable distribution profile of PSMA-914. NIR-pCLE imaging enabled real-time, single-cell-level detection of PSMA-positive tissue, visualizing tumor heterogeneity, confirmed by ex vivo microscopy and imaging. Conclusions: This preclinical proof of concept demonstrates the potential of intraoperative PSMA-specific NIR-pCLE imaging to visualize tissue structures in real time at cellular resolution. Clinical implementation could provide surgeons with valuable additional information, potentially advancing PCa patient care through improved surgical precision. Full article