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Tractography fluorescence and confocal endomicroscopy are complementary technologies to targeted tumor resection, and it is certain that as our technology for fluorescent probes continues to evolve, the confocal microscope will continue to be refined. Recent work suggests that intraoperative high-resolution augmented reality endomicroscopy, a real-time alternative to invasive biopsy and histopathology, has the potential to better quantify tumor burden at the final stages of surgery and ultimately to improve patient outcomes when combined with wide-field imaging approaches. Additional studies are needed to further elucidate the clinical benefits of these new technologies for brain tumor patients.

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This paper presents new perspectives on photonic technologies for capsule endoscopy. It first presents a review of conventional endoscopy (upper endoscopy and colonoscopy), followed by capsule endoscopy (CE), as well as their techniques, advantages, and drawbacks. The technologies for CEs presented in this paper include integration with the existing endoscopic systems that are commercially available. Such technologies include narrow-band imaging (NBI), photodynamic therapy (PDT), confocal laser endomicroscopy (CLE), optical coherence tomography (OCT), and spectroscopy in order to improve the performance of the gastrointestinal (GI) tract examination. In the context of NBI, two optical filters were designed and fabricated for integration into endoscopic capsules, allowing for the visualization of light centered at the 415 nm and 540 nm wavelengths. These optical filters are based on the principle of Fabry-Perot and were made of thin films of titanium dioxide (TiO2) and silicon dioxide (SiO2). Moreover, strategies and solutions for the adaptation of ECs for PDT are also discussed.

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BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

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Abstract Introduction: Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract's mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. Objective: This study aims to validate an eight-point score for the correct assessment of malignancy. Methods: We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. Results: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. Conclusion: The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis.

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Abstract 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 realtime analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses.

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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.

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INTRODUCTION: Confocal laser endomicroscopy is an optical imaging technique that allows in vivo, real-time, microscope-like images of the upper aerodigestive tract's mucosa. The assessment of morphological tissue characteristics for the correct differentiation between healthy and malignant suspected mucosa requires strict evaluation criteria. OBJECTIVE: This study aims to validate an eight-point score for the correct assessment of malignancy. METHODS: We performed confocal laser endomicroscopy between March and October 2020 in 13 patients. 197 sequences (11.820 images) originated from the marginal area of pharyngeal and laryngeal carcinomas. Specimens were taken at corresponding locations and analyzed in H&E staining as a standard of reference. A total of six examiners evaluated the sequences based on a scoring system; they were blinded to the histopathological examination. The primary endpoints are sensitivity, specificity, and accuracy. Secondary endpoints are interrater reliability and receiver operator characteristics. RESULTS: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. Confocal laser endomicroscopy of malignant cells demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 83.2%, 81.3%, 85.5%, 86.7%, and 79.7%, respectively, with a κ-value of 0.64, and an area under the curve of 0.86. CONCLUSION: The results confirm that this scoring system is applicable in the laryngeal and pharyngeal mucosa to classify benign and malignant tissue. A scoring system based on defined and reproducible characteristics can help translate this experimental method to broad clinical practice in head and neck diagnosis.

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BACKGROUND: Neoadjuvant chemoradiotherapy (nCRxt) followed by radical surgery is the optimal treatment for advanced rectal adenocarcinoma. Patients with clinical complete response (cCR) may be followed closely without immediate surgery. Probe-based confocal laser endomicroscopy (pCLE) is a real-time in vivo method that allows acquisition of optical biopsies with 1000 times magnification, evaluating both epithelial and vascular patterns. AIM: To evaluate the role of pCLE in the diagnosis of cCR after nCRxt for advanced rectal adenocarcinoma. METHODS: pCLE was performed in 47 patients with locally advanced rectal adenocarcinoma (T3/T4, or N+) who underwent nCRxt (5-fluorouracil, 5040 cGy). RESULTS: Twenty-seven (57.5%) patients were men, and the mean age was 62.8 years. Thirty-seven had partial response confirmed by pCLE. Ten (21.3%) patients had good endoscopic response and presented small ulcer (n = 5) or residual scar (n = 5). After nCRxt, the essential features to differentiate malignancy from post-radiation alterations at pCLE were the presence of irregular crypts, budding, back-to-back glands, cribriform pattern, increased vessel/crypt ratio, and fluorescein leakage. A scoring system was created considering these epithelial and vascular features, with high accuracy for differentiating patients with complete response from those with residual neoplasia (p < 0.00001). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 71.4%, 95.2%, 100%, and 95.7%, respectively. CONCLUSIONS: (1) pCLE evaluation of epithelial and vascular features may improve the diagnosis of cCR and may alter patient management; (2) pCLE might be valuable for identifying patients with advanced rectal cancer who will benefit from watch and wait strategy, avoiding immediate surgical treatment.

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An increase in the diagnosis of pancreatic cystic neoplasm has been described lately. Surgical treatment or surveillance is advised depending on the type of lesion diagnosed. The most accurate diagnostic approach is needed to make the best therapeutic decision. Endoscopic ultrasound is a very valuable tool in the evaluation of pancreatic cystic neoplasm. It generates high-quality images and allows the possibility of sampling the cystic fluid for cytology, microbiological and molecular evaluation. Even with this evaluation, the sensitivity of this approach is not always adequate. New technological resources have been developed to try to improve the diagnostic accuracy of pancreatic cystic neoplasms. The two most promising techniques are needle-based confocal laser endomicroscopy and contrast-enhanced harmonic endoscopic ultrasound. Needle-based confocal laser endomicroscopy allows a microscopic evaluation of mucosal glands and vascular pattern, to differentiate mucinous from non-mucinous lesions. Contrast-enhanced harmonic endoscopic ultrasound is used for the vascular evaluation of the microcirculation of the cyst wall and mural nodule, mainly to make the difference between malignant nodules and mucus plugs. A combination of these different diagnostic techniques can improve the diagnostic accuracy of pancreatic cystic neoplasms to offer the adequate therapeutic decision.

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OBJECTIVE: Probe-based confocal laser endomicroscopy (pCLE) technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and microvascular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric lesions. METHODS: Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE results. RESULTS: Patients' mean age was 68.3 (range, 42-83) years and six were men. Thirteen suspicious flat or elevated lesions (classified as 0-Is, 0-IIa or 0-IIa + IIc) and seven pre-malignant lesions (atrophy and intestinal metaplasia) were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body (n=10 lesions), the antrum (n=9) and the incisura angularis (n=1). All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% (19/20 lesions). CONCLUSIONS: pCLE is accurate for real time histology of gastric lesions. pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

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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 image-interpretation 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.

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Transanal total mesorectal excision (TME) is an emerging minimally invasive approach to rectal cancer, with encouraging preliminary results. However, the new surgical anatomy of the bottom-up approach complicates surgical understanding and increases the risks of inadvertent injuries to crucial anatomical structures, including nerves. Key elements to improve the safety and stimulate interest in such a complex technique might be robotics and image guidance, to enhance the level of precision. In this editorial, some of the technologies that could be used for precision TME are outlined, in light of the experience of our Institute for Image-Guided Surgery.

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La endomicroscopia confocal láser basada en probes (Cellvizio de Mauna Kea Technologies, París) es una nueva tecnología que permite, durante cualquier procedimiento endoscópico, realizar análisis histológicos en tiempo real (biopsia óptica), mejorando el diagnóstico y ayudando a definir el tratamiento de múltiples patologías digestivas. Es de resaltar, para nuestro medio, su utilidad en patologías de difícil diagnóstico como son las estenosis biliares indeterminadas y las neoplasias quísticas pancreáticas, cuyo diagnóstico temprano y exacto es muy difícil con las técnicas actualmente disponibles, y que es necesario para definir la realización o la exclusión de tratamientos quirúrgicos de alta morbimortalidad y alto costo, como por ejemplo, la cirugía de Whipple. En esta revisión se muestran los aportes actuales de esta tecnología, ya disponible en nuestro medio, para el diagnóstico y estudio de las patologías digestivas.

Probe based confocal laser endomicroscopy (Cellvizio Mauna Kea, Paris) is a new technology that allows performance of histological analysis (optical biopsy) during any endoscopic procedure. This improves diagnosis and helps define the treatment needed for multiple digestive diseases. Its utility for diseases that are difficult to diagnose such as indeterminate biliary strictures and pancreatic cystic neoplasms is noteworthy. Early and accurate diagnoses can be very difficult with currently available techniques, but they are exactly what are needed to determine whether or not expensive surgical treatments with great potential morbidity, for example the Whipple procedure, need to be performed. This review looks at the contribution that this technology can make in our country where it is now available for the diagnosis and study of digestive diseases.

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