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Wenda N, Wagner S, Fruth K, Fisseler-Eckhoff A, Gosepath J. Differentiating Sinonasal Tumor Entities with Fluorescein-Enhanced Confocal Laser Endomicroscopy: A Step Forward in Precision Diagnostics. Cancers (Basel) 2024; 16:4245. [PMID: 39766144 PMCID: PMC11674328 DOI: 10.3390/cancers16244245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/11/2024] [Accepted: 12/15/2024] [Indexed: 01/11/2025] Open
Abstract
Background/Objectives: Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision. Methods: Ten patients with various sinonasal malignancies, including squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, sinonasal mucosal melanoma, and endonasal lymphoma, were examined using CLE during diagnostic endoscopy. CLE images were compared descriptively with histopathological cross-sections to identify unique imaging patterns for each tumor type. Results: CLE was feasible across all cases, with high-quality images obtained despite anatomical challenges in some cases. Characteristic features, such as vascular clusters in undifferentiated carcinoma, mucin-filled bubbles in adenocarcinoma, and small round cells in neuroblastoma, were identified and corresponded well with histopathological findings. CLE also helped guide biopsies by revealing areas with diagnostic relevance. Conclusions: CLE demonstrates promise as an adjunct diagnostic tool in sinonasal malignancies, offering real-time imaging that correlates with histopathological findings and aids in targeted biopsies. While this study provides preliminary insights into the utility of CLE, further research with larger cohorts and statistical validation is necessary to establish its diagnostic reliability and broader clinical application.
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Affiliation(s)
- Nina Wenda
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | - Sebastian Wagner
- Department of Pathology, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (S.W.); (A.F.-E.)
| | - Kai Fruth
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | | | - Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
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Evola G, Vacante M, Evola FR. Confocal laser endomicroscopy as a new diagnostic tool for poorly differentiated gastric adenocarcinoma. World J Clin Cases 2024; 12:5845-5849. [PMID: 39286386 PMCID: PMC11287494 DOI: 10.12998/wjcc.v12.i26.5845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 05/07/2024] [Accepted: 06/05/2024] [Indexed: 07/19/2024] Open
Abstract
Gastric cancer (GC) is a multifactorial disease, where both environmental and genetic features can have an impact on its occurrence and development. GC represents one of the leading causes of cancer-related deaths worldwide. GC is most frequent in males and is believed to arise from a series of premalignant lesions. The detection of GC at an early stage is crucial because early GC, which is an invasive stomach cancer confined to the mucosal or submucosal lining, may be curable with a reported 5-year survival rate of more than 90%. Advanced GC usually has a poor prognosis despite current treatment standards. The diagnostic efficacy of conventional endoscopy (with light endoscopy) is currently limited. Confocal laser endomicroscopy is a novel imaging technique that allows real-time in vivo histological examination of mucosal surfaces during endoscopy. Confocal laser endomicroscopy may be of great importance in the surveillance of precancerous gastric lesions and in the diagnosis of GC. In this editorial we commented on the article about this topic published by Lou et al in the recent issue of the World Journal of Clinical Cases.
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Affiliation(s)
- Giuseppe Evola
- Department of Surgery, "Garibaldi" Hospital, Catania 95100, Italy
| | - Marco Vacante
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania 95123, Italy
| | - Francesco R Evola
- Department of Surgery, Division of Orthopedics and Trauma Surgery, “Cannizzaro” Hospital, Catania 95100, Italy
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3
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Wenda N, Fruth K, Wagner S, Fisseler-Eckhoff A, Gosepath J. Confocal Laser Endomicroscopy in Resection of Sinonasal Malignant Melanoma-Preliminary Report on Real-Time Margin Assessment and Support in Surgical Decision-Making. J Clin Med 2024; 13:4483. [PMID: 39124751 PMCID: PMC11312853 DOI: 10.3390/jcm13154483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Background/Objectives: Building upon the rising value of Confocal Laser Endomicroscopy (CLE) in squamous cell carcinoma of the head and neck, we present the first application of CLE during the resection of sinonasal malignant melanomas. This study aims to evaluate the potential of CLE to assist surgeons in intraoperative decision-making, with a particular focus on resection margin assessment within the constrained nasal cavity. Methods: Two cases of sinonasal malignant melanoma were included in this study. CLE was employed to examine visible tumors and their margins, both pre- and post-endoscopic resection. The findings were compared to histopathological results as well as data on squamous cell carcinoma, for which malignancy criteria had already been established in prior projects. Results: CLE provided the real-time visualization of sinonasal malignant melanomas and their margins, successfully differentiating between healthy and neoplastic tissue compared to histopathological findings. Conclusion: CLE offers the potential for real-time assessment, aiding surgeons in more precise tumor resection and potentially improving patient outcomes. This study demonstrates the feasibility of using CLE in the resection of sinonasal malignant melanoma, highlighting its ability to differentiate between healthy and neoplastic tissue intraoperatively.
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Affiliation(s)
- Nina Wenda
- Department of Otolaryngology, Head and Neck Surgery, Horst Schmidt Kliniken, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | - Kai Fruth
- Department of Otolaryngology, Head and Neck Surgery, Horst Schmidt Kliniken, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | - Sebastian Wagner
- Department of Pathology, Helios HSK, 65199 Wiesbaden, Germany; (S.W.); (A.F.-E.)
| | | | - Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, Horst Schmidt Kliniken, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
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Matsubayashi CO, Cheng S, Hulchafo I, Zhang Y, Tada T, Buxbaum JL, Ochiai K. Artificial intelligence for gastric cancer in endoscopy: From diagnostic reasoning to market. Dig Liver Dis 2024; 56:1156-1163. [PMID: 38763796 DOI: 10.1016/j.dld.2024.04.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 05/21/2024]
Abstract
Recognition of gastric conditions during endoscopy exams, including gastric cancer, usually requires specialized training and a long learning curve. Besides that, the interobserver variability is frequently high due to the different morphological characteristics of the lesions and grades of mucosal inflammation. In this sense, artificial intelligence tools based on deep learning models have been developed to support physicians to detect, classify, and predict gastric lesions more efficiently. Even though a growing number of studies exists in the literature, there are multiple challenges to bring a model to practice in this field, such as the need for more robust validation studies and regulatory hurdles. Therefore, the aim of this review is to provide a comprehensive assessment of the current use of artificial intelligence applied to endoscopic imaging to evaluate gastric precancerous and cancerous lesions and the barriers to widespread implementation of this technology in clinical routine.
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Affiliation(s)
- Carolina Ogawa Matsubayashi
- Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, University of São Paulo, São Paulo, Brasil; AI Medical Service Inc., Tokyo, Japan.
| | - Shuyan Cheng
- Department of Population Health Science, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ismael Hulchafo
- Columbia University School of Nursing, New York, NY 10032, USA
| | - Yifan Zhang
- Department of Population Health Science, Weill Cornell Medical College, New York, NY 10065, USA
| | - Tomohiro Tada
- AI Medical Service Inc., Tokyo, Japan; Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Kentaro Ochiai
- Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Colon and Rectal Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Oetter N, Pröll J, Sievert M, Goncalves M, Rohde M, Nobis CP, Knipfer C, Aubreville M, Pan Z, Breininger K, Maier A, Kesting M, Stelzle F. Oral mucosa - an examination map for confocal laser endomicroscopy within the oral cavity: an experimental clinical study. Clin Oral Investig 2024; 28:266. [PMID: 38652317 PMCID: PMC11039507 DOI: 10.1007/s00784-024-05664-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 04/16/2024] [Indexed: 04/25/2024]
Abstract
OBJECTIVES Confocal laser endomicroscopy (CLE) is an optical method that enables microscopic visualization of oral mucosa. Previous studies have shown that it is possible to differentiate between physiological and malignant oral mucosa. However, differences in mucosal architecture were not taken into account. The objective was to map the different oral mucosal morphologies and to establish a "CLE map" of physiological mucosa as baseline for further application of this powerful technology. MATERIALS AND METHODS The CLE database consisted of 27 patients. The following spots were examined: (1) upper lip (intraoral) (2) alveolar ridge (3) lateral tongue (4) floor of the mouth (5) hard palate (6) intercalary line. All sequences were examined by two CLE experts for morphological differences and video quality. RESULTS Analysis revealed clear differences in image quality and possibility of depicting tissue morphologies between the various localizations of oral mucosa: imaging of the alveolar ridge and hard palate showed visually most discriminative tissue morphology. Labial mucosa was also visualized well using CLE. Here, typical morphological features such as uniform cells with regular intercellular gaps and vessels could be clearly depicted. Image generation and evaluation was particularly difficult in the area of the buccal mucosa, the lateral tongue and the floor of the mouth. CONCLUSION A physiological "CLE map" for the entire oral cavity could be created for the first time. CLINICAL RELEVANCE This will make it possible to take into account the existing physiological morphological features when differentiating between normal mucosa and oral squamous cell carcinoma in future work.
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Affiliation(s)
- Nicolai Oetter
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany.
- SAOT‑Erlangen Graduate School in Advanced Optical Technologies, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Paul Gordan Straße 6, 91052, Erlangen, Germany.
| | - Jonas Pröll
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany
| | - Matti Sievert
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Waldstraße 1, 91054, Erlangen, Germany
| | - Miguel Goncalves
- Department of Otorhinolaryngology, Head and Neck Surgery, Julius-Maximilians University Würzburg, University Hospital Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany
| | - Maximilian Rohde
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany
- SAOT‑Erlangen Graduate School in Advanced Optical Technologies, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Paul Gordan Straße 6, 91052, Erlangen, Germany
| | - Christopher-Philipp Nobis
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany
| | - Christian Knipfer
- Department of Oral and Maxillofacial Surgery, University Hamburg, University Medical Center Hamburg- Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Marc Aubreville
- Technische Hochschule Ingolstadt, Esplanade 10, 85049, Ingolstadt, Germany
| | - Zhaoya Pan
- Pattern Recognition Lab, Department of Computer Science, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Martensstraße 3, 91058, Erlangen, Germany
| | - Katharina Breininger
- Department Artificial Intelligence in Biomedical Engineering, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Henkestraße 91, 91052, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Lab, Department of Computer Science, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Martensstraße 3, 91058, Erlangen, Germany
| | - Marco Kesting
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany
- SAOT‑Erlangen Graduate School in Advanced Optical Technologies, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Paul Gordan Straße 6, 91052, Erlangen, Germany
| | - Florian Stelzle
- Department of Oral and Maxillofacial Surgery, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), University Hospital Erlangen, Glückstraße 11, 91054, Erlangen, Germany
- SAOT‑Erlangen Graduate School in Advanced Optical Technologies, Friedrich‑Alexander University Erlangen‑Nürnberg (FAU), Paul Gordan Straße 6, 91052, Erlangen, Germany
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Xia J, Jiang B, Pan J, Liao Z. Imaging of gastrointestinal endoscopy. TRANSPATHOLOGY 2024:171-183. [DOI: 10.1016/b978-0-323-95223-1.00026-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wenda N, Fruth K, Fisseler-Eckhoff A, Gosepath J. The Multifaceted Role of Confocal Laser Endomicroscopy in Head and Neck Surgery: Oncologic and Functional Insights. Diagnostics (Basel) 2023; 13:3081. [PMID: 37835824 PMCID: PMC10572220 DOI: 10.3390/diagnostics13193081] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/20/2023] [Accepted: 09/26/2023] [Indexed: 10/15/2023] Open
Abstract
(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE's potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE's expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.
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Affiliation(s)
- Nina Wenda
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | - Kai Fruth
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
| | | | - Jan Gosepath
- Department of Otolaryngology, Head and Neck Surgery, Helios HSK Wiesbaden, 65199 Wiesbaden, Germany; (K.F.); (J.G.)
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8
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Sievert M, Mantsopoulos K, Mueller SK, Rupp R, Eckstein M, Stelzle F, Oetter N, Maier A, Aubreville M, Iro H, Goncalves M. Validation of a classification and scoring system for the diagnosis of laryngeal and pharyngeal squamous cell carcinomas by confocal laser endomicroscopy. Braz J Otorhinolaryngol 2022; 88 Suppl 4:S26-S32. [PMID: 34348858 DOI: 10.1016/j.bjorl.2021.06.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 06/16/2021] [Accepted: 06/20/2021] [Indexed: 12/14/2022] Open
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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Affiliation(s)
- Matti Sievert
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, Germany
| | - Konstantinos Mantsopoulos
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, Germany
| | - Sarina K Mueller
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, Germany
| | - Robin Rupp
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Florian Stelzle
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Maxillofacial Surgery, Erlangen, Germany
| | - Nicolai Oetter
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Maxillofacial Surgery, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Marc Aubreville
- Institute of Image Understanding and Medical Application of Artificial Intelligence, Technische Hochschule, Ingolstadt, Germany
| | - Heinrich Iro
- Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Department of Otorhinolaryngology, Head and Neck Surgery, Erlangen, Germany
| | - Miguel Goncalves
- University Hospital Aachen, RWTH Aachen University, Department of Otorhinolaryngology, Head and Neck Surgery, Germany.
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Kim Y, Kim H, Jung M, Rha SY, Chung HC, Lee SK. Probe-Based Confocal Laser Endomicroscopy versus White-Light Endoscopy with Narrow-Band Imaging for Predicting and Collecting Residual Cancer Tissue in Patients with Gastric Cancer Receiving Chemotherapy. Cancers (Basel) 2022; 14:4319. [PMID: 36077854 PMCID: PMC9454914 DOI: 10.3390/cancers14174319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/29/2022] [Accepted: 09/02/2022] [Indexed: 12/24/2022] Open
Abstract
In cases of progression despite chemotherapy, collecting gastric cancer (GC) tissues might be helpful for molecular biology research or the development of new target drugs for treating cases that are refractory to chemotherapy. Chemotherapy, however, may reduce or alter the distribution of GC tissue on the surface, making the detection of GC tissue during upper endoscopy challenging. Probe-based confocal laser endomicroscopy (pCLE) is a new technology that enables histological diagnosis by magnifying the mucous membrane to a microscopic level. Here, we evaluated whether pCLE could increase the yield of endoscopic biopsy for GC compared to white-light endoscopy (WLE) with magnifying narrow-band imaging (M-NBI) in GC patients receiving chemotherapy with its powerful imaging technique. Patients underwent WLE/M-NBI and pCLE for the detection of residual GC for the purpose of response evaluation or clinical trial registration. After WLE/M-NBI and pCLE, each residual GC lesion was biopsied for histological analysis. A total of 23 patients were enrolled between January 2018 and June 2020. Overall, pCLE showed significantly higher sensitivity and negative predictive value than WLE/M-NBI. The accuracy of pCLE was superior to that of WLE/M-NBI. Moreover, pCLE showed better predictive ability for residual GC than WLE/M-NBI, while WLE/M-NBI and pCLE showed inconsistent results. pCLE diagnosed residual GC more accurately than WLE/M-NBI, which resulted in an increased number of GC tissues collected during the endoscopic biopsy.
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Affiliation(s)
- Yuna Kim
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
| | - Hyunki Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Minkyu Jung
- Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sun Young Rha
- Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Hyun Cheol Chung
- Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
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Maione F, Chini A, Maione R, Manigrasso M, Marello A, Cassese G, Gennarelli N, Milone M, De Palma GD. Endoscopic Diagnosis and Management of Barrett's Esophagus with Low-Grade Dysplasia. Diagnostics (Basel) 2022; 12:1295. [PMID: 35626450 PMCID: PMC9141542 DOI: 10.3390/diagnostics12051295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 02/05/2023] Open
Abstract
Barrett's Esophagus is a common condition associated with chronic gastroesophageal reflux disease. It is well known that it has an association with a higher incidence of esophageal adenocarcinoma, but this neoplastic transformation is first preceded by the onset of low and high-grade dysplasia. The evaluation of low grade dysplastic esophageal mucosa is still controversial; although endoscopic surveillance is preferred, several minimally invasive endoscopic therapeutic approaches are available. Endoscopic mucosal resection and radiofrequency ablation are the most used endoscopic treatments for the eradication of low-grade dysplasia, respectively, for nodular and flat dysplasia. Novel endoscopic treatments are cryotherapy ablation and argon plasma coagulation, that have good rates of eradication with less complications and post-procedural pain.
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Affiliation(s)
- Francesco Maione
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Alessia Chini
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Rosa Maione
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Michele Manigrasso
- Department of Advanced Biomedical Sciences, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Alessandra Marello
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Gianluca Cassese
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Nicola Gennarelli
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Marco Milone
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
| | - Giovanni Domenico De Palma
- Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy; (A.C.); (A.M.); (G.C.); (N.G.); (M.M.); (G.D.D.P.)
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Horgan CC, Jensen M, Chiappini C, Vercauteren T, Cook R, Bergholt MS. Hybrid confocal Raman endomicroscopy for morpho-chemical tissue characterization. BIOMEDICAL OPTICS EXPRESS 2022; 13:2278-2285. [PMID: 35519240 PMCID: PMC9045932 DOI: 10.1364/boe.449110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 02/06/2022] [Accepted: 02/09/2022] [Indexed: 06/14/2023]
Abstract
Confocal laser endomicroscopy (CLE) offers imaging of tissue microarchitecture and has emerged as a promising tool for in vivo clinical diagnosis of cancer across many organs. CLE, however, can show high inter-observer dependency and does not provide information about tissue molecular composition. In contrast, Raman spectroscopy is a label-free optical technique that provides detailed biomolecular compositional information but offers limited or no morphological information. Here we present a novel hybrid fiber-optic confocal Raman endomicroscopy system for morpho-chemical tissue imaging and analysis. The developed confocal endomicroscopy system is based on a novel detection scheme for rejecting Raman silica fiber interference permitting simultaneous CLE imaging and Raman spectral acquisition of tissues through a coherent fiber bundle. We show that this technique enables real-time microscopic visualization of tissue architecture as well as simultaneous pointwise label-free biomolecular characterization and fingerprinting of tissue paving the way for multimodal diagnostics at endoscopy.
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Affiliation(s)
- Conor C. Horgan
- Centre for Craniofacial and Regenerative Biology, King’s College London, London SE1 9RT, UK
| | - Magnus Jensen
- Centre for Craniofacial and Regenerative Biology, King’s College London, London SE1 9RT, UK
| | - Ciro Chiappini
- Centre for Craniofacial and Regenerative Biology, King’s College London, London SE1 9RT, UK
- London Centre for Nanotechnology, King’s College London, London WC2R 2LS, UK
| | - Tom Vercauteren
- School of Biomedical Engineering and Imaging Sciences, King's College London, London WC2R 2LS, UK
| | - Richard Cook
- Centre for Oral, Clinical and Translational Sciences, King’s College London, London SE1 9RT, UK
| | - Mads S. Bergholt
- Centre for Craniofacial and Regenerative Biology, King’s College London, London SE1 9RT, UK
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Sievert M, Aubreville M, Gostian AO, Mantsopoulos K, Koch M, Mueller SK, Eckstein M, Rupp R, Stelzle F, Oetter N, Maier A, Iro H, Goncalves M. Validity of tissue homogeneity in confocal laser endomicroscopy on the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2022; 279:4147-4156. [PMID: 35226181 PMCID: PMC9249707 DOI: 10.1007/s00405-022-07304-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 02/07/2022] [Indexed: 12/29/2022]
Abstract
Purpose Confocal laser endomicroscopy (CLE) allows imaging of the laryngeal mucosa in a thousand-fold magnification. This study analyzes differences in tissue homogeneity between healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included five SCC patients with planned total laryngectomy in this study between October 2020 and February 2021. We captured CLE scans of the tumor and healthy mucosa. Analysis of image homogeneity to diagnose SCC was performed by measuring the signal intensity in four regions of interest (ROI) in each frame in a total of 60 sequences. Each sequence was assigned to the corresponding histological pattern, derived from hematoxylin and eosin staining. In addition, we recorded the subjective evaluation of seven investigators regarding tissue homogeneity. Results Out of 3600 images, 1620 (45%) correlated with benign mucosa and 1980 (55%) with SCC. ROIs of benign mucosa and SCC had a mean and standard deviation (SD) of signal intensity of, respectively, 232.1 ± 3.34 and 467.3 ± 9.72 (P < 0.001). The mean SD between the four different ROIs was 39.1 ± 1.03 for benign and 101.5 ± 2.6 for SCC frames (P < 0.001). In addition, homogeneity yielded a sensitivity and specificity of 81.8% and 86.2%, respectively, regarding the investigator-dependent analysis. Conclusions SCC shows a significant tissue inhomogeneity in comparison to the healthy epithelium. The results support this feature’s importance in identifying malignant mucosa areas during CLE examination. However, the examiner-dependent evaluation emphasizes that homogeneity is a sub-criterion that must be considered in a broad context.
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Affiliation(s)
- Matti Sievert
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany.
| | | | - Antoniu-Oreste Gostian
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Konstantinos Mantsopoulos
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Michael Koch
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Sarina Katrin Mueller
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Robin Rupp
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Florian Stelzle
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Nicolai Oetter
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Laboratory, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Heinrich Iro
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Miguel Goncalves
- Department of Otorhinolaryngology, Plastic Head and Neck Surgery, Rheinische Westfälische Technische Hochschule Aachen, University Hospital, Aachen, Germany
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Ellebrecht DB, von Weihe S. Endoscopic confocal laser-microscopy for the intraoperative nerve recognition: is it feasible? BIOMED ENG-BIOMED TE 2021; 67:11-17. [PMID: 34913620 DOI: 10.1515/bmt-2021-0171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 11/26/2021] [Indexed: 11/15/2022]
Abstract
Surgeons lose most of their tactile tissue information during minimal invasive surgery and need an additional tool of intraoperative tissue recognition. Confocal laser microscopy (CLM) is a well-established method of tissue investigation. The objective of this study was to analyze the feasibility and diagnostic accuracy of CLM nervous tissue recognition. Images taken with an endoscopic CLM system of sympathetic ganglions, nerve fibers and pleural tissue were characterized in terms of specific signal-patterns ex-vivo. No fluorescent dye was used. Diagnostic accuracy of tissue classification was evaluated by newly trained observers (sensitivity, specificity, PPV, NPV and interobserver variability). Although CLM images showed low CLM image contrast, assessment of nerve tissue was feasible without any fluorescent dye. Sensitivity and specificity ranged between 0.73 and 0.9 and 0.55-1.0, respectively. PPVs were 0.71-1.0 and the NPV range was between 0.58 and 0.86. The overall interobserver variability was 0.36. The eCLM enables to evaluate nervous tissue and to distinguish between nerve fibers, ganglions and pleural tissue based on backscattered light. However, the low image contrast and the heterogeneity in correct tissue diagnosis and a fair interobserver variability indicate the limit of CLM imaging without any fluorescent dye.
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Affiliation(s)
| | - Sönke von Weihe
- Department of Thoracic Surgery, LungClinic Großhansdorf, Wöhrendamm 80, 22927 Großhansdorf, Germany
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Diagnostic Accuracy of Confocal Laser Endomicroscopy for the Diagnosis of Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182312390. [PMID: 34886116 PMCID: PMC8657406 DOI: 10.3390/ijerph182312390] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/18/2021] [Accepted: 11/18/2021] [Indexed: 01/22/2023]
Abstract
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.
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Sievert M, Auberville M, Oetter N, Stelzle F, Maier A, Mantsopoulos K, Iro H, Goncalves M. [Confocal laser endomicroscopy of head and neck squamous cell carcinoma: a systematic review]. Laryngorhinootologie 2021; 100:875-881. [PMID: 33401329 DOI: 10.1055/a-1339-1635] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Confocal laser endomicroscopy (CLE), with a magnification of up to 1000 ×, offers the possibility to visualize intercellular spaces in vivo. CLE has already established itself in different disciplines. This article gives an overview of the current research on CLE in the diagnosis of the head and neck squamous cell carcinoma. MATERIAL AND METHODS Systematic bibliographic research in the following online databases: PubMed, MEDLINE, Thompson Reuters Web of Science, SPIE using the following keywords: confocal laser endomicroscopy, CLE, endomicroscopy, head and neck, larynx. Evaluation of the scientific relevance according to defined criteria. RESULTS All studies were analyzed concerning the clinical application, clinical findings, and computer-aided data processing. CONCLUSIONS The recently published data suggest that CLE has a high potential to improve the diagnosis of malignant mucosal lesions in the upper aerodigestive tract.
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Affiliation(s)
- Matti Sievert
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Marc Auberville
- Bildverstehen und medizinische Anwendung der künstlichen Intelligenz, Fakultät Informatik, Technische Hochschule Ingolstadt, Deutschland
| | - Nicolai Oetter
- Klinik und Poliklinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Florian Stelzle
- Klinik und Poliklinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Andreas Maier
- Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Konstantinos Mantsopoulos
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Heinrich Iro
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
| | - Miguel Goncalves
- Hals-Nasen-Ohrenklinik, Kopf- und Hals-Chirurgie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Deutschland
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Sievert M, Stelzle F, Aubreville M, Mueller SK, Eckstein M, Oetter N, Maier A, Mantsopoulos K, Iro H, Goncalves M. Intraoperative free margins assessment of oropharyngeal squamous cell carcinoma with confocal laser endomicroscopy: a pilot study. Eur Arch Otorhinolaryngol 2021; 278:4433-4439. [PMID: 33582849 PMCID: PMC8486707 DOI: 10.1007/s00405-021-06659-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Accepted: 01/29/2021] [Indexed: 12/20/2022]
Abstract
PURPOSE This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with confocal laser endomicroscopy (CLE) during oropharyngeal squamous cell carcinoma (OPSCC) surgery. METHODS We included five consecutive patients confirmed OPSCC and planned tumor resection in September and October 2020. Healthy appearing mucosa in the marginal zone, and the tumor margin, were examined with CLE and biopsy during tumor resection. A total of 12,809 CLE frames were correlated with the gold standard of hematoxylin and eosin staining. Three head and neck surgeons and one pathologist were asked to identify carcinoma in a sample of 169 representative images, blinded to the histological results. RESULTS Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of OPSCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 86%, 90%, 79%, 88%, and 82%, respectively, with inter-rater reliability and κ-value of 0.60. CONCLUSION CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the oropharynx for evaluation and demarcation of cancer. It can eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.
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Affiliation(s)
- Matti Sievert
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Erlangen-Nuremberg, Germany, Waldstrasse 1, 91054, Erlangen, Germany.
| | - Florian Stelzle
- Department of Maxillofacial Surgery, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Marc Aubreville
- Institute of Image Understanding and Medical Application of Artificial Intelligence, Technische Hochschule, Ingolstadt, Germany
| | - Sarina K Mueller
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Erlangen-Nuremberg, Germany, Waldstrasse 1, 91054, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Nicolai Oetter
- Department of Maxillofacial Surgery, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Laboratory, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Konstantinos Mantsopoulos
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Erlangen-Nuremberg, Germany, Waldstrasse 1, 91054, Erlangen, Germany
| | - Heinrich Iro
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Erlangen-Nuremberg, Germany, Waldstrasse 1, 91054, Erlangen, Germany
| | - Miguel Goncalves
- Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Erlangen-Nuremberg, Germany, Waldstrasse 1, 91054, Erlangen, Germany
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Sievert M, Eckstein M, Mantsopoulos K, Mueller SK, Stelzle F, Aubreville M, Oetter N, Maier A, Iro H, Goncalves M. Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2021; 279:2029-2037. [PMID: 34185145 PMCID: PMC8930873 DOI: 10.1007/s00405-021-06954-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE Confocal laser endomicroscopy (CLE) allows surface imaging of the laryngeal and pharyngeal mucosa in vivo at a thousand-fold magnification. This study aims to compare irregular blood vessels and intraepithelial capillary loops in healthy mucosa and squamous cell carcinoma (SCC) via CLE. MATERIALS AND METHODS We included ten patients with confirmed SCC and planned total laryngectomy in this study between March 2020 and February 2021. CLE images of these patients were collected and compared with the corresponding histology in hematoxylin and eosin staining. We analyzed the characteristic endomicroscopic patterns of blood vessels and intraepithelial capillary loops for the diagnosis of SCC. RESULTS In a total of 54 sequences, we identified 243 blood vessels which were analyzed regarding structure, diameter, and Fluorescein leakage, confirming that irregular, corkscrew-like vessels (24.4% vs. 1.3%; P < .001), dilated intraepithelial capillary loops (90.8% vs. 28.7%; P < .001), and increased capillary leakage (40.7% vs. 2.5%; P < .001), are significantly more frequently detected in SCC compared to the healthy epithelium. We defined a vessel diameter of 30 μm in capillary loops as a cut-off value, obtaining a sensitivity, specificity, PPV, and NPV and accuracy of 90.6%, 71.3%, 57.4%, 94.7%, and 77.1%, respectively, for the detection of malignancy based solely on capillary architecture. CONCLUSION Capillaries within malignant lesions are fundamentally different from those in healthy mucosa regions. The capillary architecture is a significant feature aiding the identification of malignant mucosa areas during in-vivo, real-time CLE examination.
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Affiliation(s)
- Matti Sievert
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany.
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Konstantinos Mantsopoulos
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Sarina K Mueller
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Florian Stelzle
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Marc Aubreville
- Institute of Image Understanding and Medical Application of Artificial Intelligence, Technische Hochschule, Ingolstadt, Germany
| | - Nicolai Oetter
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Heinrich Iro
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
| | - Miguel Goncalves
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstrasse 1, 91054, Erlangen, Germany
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Sievert M, Oetter N, Aubreville M, Stelzle F, Maier A, Eckstein M, Mantsopoulos K, Gostian AO, Mueller SK, Koch M, Agaimy A, Iro H, Goncalves M. Feasibility of intraoperative assessment of safe surgical margins during laryngectomy with confocal laser endomicroscopy: A pilot study. Auris Nasus Larynx 2021; 48:764-769. [PMID: 33468350 DOI: 10.1016/j.anl.2021.01.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/24/2020] [Accepted: 01/04/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVE This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy. METHODS Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining). RESULTS Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected. CONCLUSION CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.
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Affiliation(s)
- Matti Sievert
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Nicolai Oetter
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Marc Aubreville
- Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Florian Stelzle
- Department of Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Andreas Maier
- Pattern Recognition Lab, Computer Science, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Markus Eckstein
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Konstantinos Mantsopoulos
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Antoniu-Oreste Gostian
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Sarina K Mueller
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Michael Koch
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Abbas Agaimy
- Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Erlangen, Germany
| | - Heinrich Iro
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany
| | - Miguel Goncalves
- Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital, Waldstraße 1, 91054 Erlangen, Germany.
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Goyal H, Mann R, Gandhi Z, Perisetti A, Ali A, Aman Ali K, Sharma N, Saligram S, Tharian B, Inamdar S. Scope of Artificial Intelligence in Screening and Diagnosis of Colorectal Cancer. J Clin Med 2020; 9:3313. [PMID: 33076511 PMCID: PMC7602532 DOI: 10.3390/jcm9103313] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/09/2020] [Accepted: 10/12/2020] [Indexed: 12/15/2022] Open
Abstract
Globally, colorectal cancer is the third most diagnosed malignancy. It causes significant mortality and morbidity, which can be reduced by early diagnosis with an effective screening test. Integrating artificial intelligence (AI) and computer-aided detection (CAD) with screening methods has shown promising colorectal cancer screening results. AI could provide a "second look" for endoscopists to decrease the rate of missed polyps during a colonoscopy. It can also improve detection and characterization of polyps by integration with colonoscopy and various advanced endoscopic modalities such as magnifying narrow-band imaging, endocytoscopy, confocal endomicroscopy, laser-induced fluorescence spectroscopy, and magnifying chromoendoscopy. This descriptive review discusses various AI and CAD applications in colorectal cancer screening, polyp detection, and characterization.
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Affiliation(s)
- Hemant Goyal
- Department of Internal Medicine, The Wright Center for Graduate Medical Education, Scranton, PA 18505, USA
| | | | - Zainab Gandhi
- Department of Medicine, Geisinger Community Medical Center, Scranton, PA 18510, USA;
| | - Abhilash Perisetti
- Department of Gastroenterology and Hepatology, The University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;
| | - Aman Ali
- Division of Gastroenterology, The Commonwealth Medical College, Wilkes Barre General Hospital, Wilkes-Barre, PA 18764, USA;
- Digestive Care Associates, Kingston, PA 18704, USA;
| | | | - Neil Sharma
- Division of Interventional Oncology & Surgical Endoscopy (IOSE), Parkview Cancer Institute, Fort Wayne, IN 46845, USA;
- Division of Interventional Oncology & Surgical Endoscopy, Indiana University School of Medicine, Fort Wayne, IN 46805, USA
| | - Shreyas Saligram
- Department of Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA;
| | - Benjamin Tharian
- General and Advanced Endoscopy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;
| | - Sumant Inamdar
- Advanced Endoscopy Fellowship, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;
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Etievant A, Monnin J, Lihoreau T, Tamadazte B, Rougeot P, Magnin E, Tavernier L, Pazart L, Haffen E. Comparison of Noninvasive Imagery Methods to Observe Healthy and Degenerated Olfactory Epithelium in Mice for the Early Diagnosis of Neurodegenerative Diseases. Front Neuroanat 2020; 14:34. [PMID: 32760253 PMCID: PMC7371997 DOI: 10.3389/fnana.2020.00034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 05/28/2020] [Indexed: 11/13/2022] Open
Abstract
Olfactory dysfunction could be an early and reliable indicator for the diagnosis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. In this paper, we compare the potential of different noninvasive medical imaging modalities (optical coherence tomography, confocal microscopy, and fluorescence endomicroscopy) to distinguish how the olfactory epithelium, both at the cellular and the structural levels, is altered. Investigations were carried out on three experimental groups: two pathological groups (mice models with deliberately altered olfactory epithelium and Alzheimer's disease transgenic mice models) were compared with healthy mice models. As histological staining, the three tested noninvasive imaging tools demonstrated the general tubular organization of the olfactory epithelium on healthy mice. Contrary to OCT, confocal microscopy, and endomicroscopy allowed visualizing the inner structure of olfactory epithelium as well as its morphological or functional changes on pathological models, alterations classically observed with histological assessment. The results could lead to relevant development of imaging tools for noninvasive and early diagnosis of neurodegenerative diseases through the in situ characterization of the olfactory epithelium.
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Affiliation(s)
- Adeline Etievant
- Laboratoire de Neurosciences Intégratives et Cliniques, Université Bourgogne-Franche-Comté, Université de Franche-Comté, Besançon, France
| | - Julie Monnin
- Laboratoire de Neurosciences Intégratives et Cliniques, Université Bourgogne-Franche-Comté, Université de Franche-Comté, Besançon, France.,CHU Besançon, INSERM, CIC 1431, Centre d'Investigation Clinique, Besançon, France
| | - Thomas Lihoreau
- CHU Besançon, INSERM, CIC 1431, Centre d'Investigation Clinique, Besançon, France
| | - Brahim Tamadazte
- FEMTO-ST, Dép. AS2M, CNRS, Université Bourgogne Franche-Comté, 24 rue Savary, Besançon, France.,Institut des Systémes Intelligents et de Robotique, Sorbonne Université, CNRS, UMR 7222, Paris, France
| | - Patrick Rougeot
- FEMTO-ST, Dép. AS2M, CNRS, Université Bourgogne Franche-Comté, 24 rue Savary, Besançon, France
| | - Eloi Magnin
- Laboratoire de Neurosciences Intégratives et Cliniques, Université Bourgogne-Franche-Comté, Université de Franche-Comté, Besançon, France
| | - Laurent Tavernier
- Service d'oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, CHU Besançon, Université Bourgogne-Franche-Comté, Besançon, France
| | - Lionel Pazart
- Laboratoire de Neurosciences Intégratives et Cliniques, Université Bourgogne-Franche-Comté, Université de Franche-Comté, Besançon, France.,CHU Besançon, INSERM, CIC 1431, Centre d'Investigation Clinique, Besançon, France
| | - Emmanuel Haffen
- Laboratoire de Neurosciences Intégratives et Cliniques, Université Bourgogne-Franche-Comté, Université de Franche-Comté, Besançon, France.,CHU Besançon, INSERM, CIC 1431, Centre d'Investigation Clinique, Besançon, France
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21
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Sukhikh MV, Panchenkov DN. [Confocal laser endomicroscopy of the upper digestive tract: history of development and screening]. Khirurgiia (Mosk) 2020:42-46. [PMID: 32352667 DOI: 10.17116/hirurgia202004142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Confocal laser endomicroscopy is an endoscopic diagnostic technique developed for real-time histological diagnosis of gastrointestinal diseases. This review is devoted to analysis of confocal laser endomicroscopy in diagnosis of gastrointestinal diseases, especially for screening or monitoring of gastrointestinal neoplasia.
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Affiliation(s)
- M V Sukhikh
- A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of Russia, Moscow, Russia
| | - D N Panchenkov
- A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of Russia, Moscow, Russia
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22
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Ellebrecht DB, Latus S, Schlaefer A, Keck T, Gessert N. Towards an Optical Biopsy during Visceral Surgical Interventions. Visc Med 2020; 36:70-79. [PMID: 32355663 DOI: 10.1159/000505938] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 01/13/2020] [Indexed: 12/24/2022] Open
Abstract
Background Cancer will replace cardiovascular diseases as the most frequent cause of death. Therefore, the goals of cancer treatment are prevention strategies and early detection by cancer screening and ideal stage therapy. From an oncological point of view, complete tumor resection is a significant prognostic factor. Optical coherence tomography (OCT) and confocal laser microscopy (CLM) are two techniques that have the potential to complement intraoperative frozen section analysis as in vivo and real-time optical biopsies. Summary In this review we present both procedures and review the progress of evaluation for intraoperative application in visceral surgery. For visceral surgery, there are promising studies evaluating OCT and CLM; however, application during routine visceral surgical interventions is still lacking. Key Message OCT and CLM are not competing but complementary approaches of tissue analysis to intraoperative frozen section analysis. Although intraoperative application of OCT and CLM is at an early stage, they are two promising techniques of intraoperative in vivo and real-time tissue examination. Additionally, deep learning strategies provide a significant supplement for automated tissue detection.
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Affiliation(s)
- David Benjamin Ellebrecht
- LungenClinic Grosshansdorf, Department of Thoracic Surgery, Grosshansdorf, Germany.,University Medical Center Schleswig-Holstein, Campus Lübeck, Department of Surgery, Lübeck, Germany
| | - Sarah Latus
- Hamburg University of Technology, Institute of Medical Technology, Hamburg, Germany
| | - Alexander Schlaefer
- Hamburg University of Technology, Institute of Medical Technology, Hamburg, Germany
| | - Tobias Keck
- University Medical Center Schleswig-Holstein, Campus Lübeck, Department of Surgery, Lübeck, Germany
| | - Nils Gessert
- Hamburg University of Technology, Institute of Medical Technology, Hamburg, Germany
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23
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Glover B, Teare J, Patel N. The Status of Advanced Imaging Techniques for Optical Biopsy of Colonic Polyps. Clin Transl Gastroenterol 2020; 11:e00130. [PMID: 32352708 PMCID: PMC7145035 DOI: 10.14309/ctg.0000000000000130] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 01/03/2020] [Indexed: 12/19/2022] Open
Abstract
The progressive miniaturization of photonic components presents the opportunity to obtain unprecedented microscopic images of colonic polyps in real time during endoscopy. This information has the potential to act as "optical biopsy" to aid clinical decision-making, including the possibility of adopting new paradigms such as a "resect and discard" approach for low-risk lesions. The technologies discussed in this review include confocal laser endomicroscopy, optical coherence tomography, multiphoton microscopy, Raman spectroscopy, and hyperspectral imaging. These are in different stages of development and clinical readiness, but all show the potential to produce reliable in vivo discrimination of different tissue types. A structured literature search of the imaging techniques for colorectal polyps has been conducted. The significant developments in endoscopic imaging were identified for each modality, and the status of current development was discussed. Of the advanced imaging techniques discussed, confocal laser endomicroscopy is in clinical use and, under optimal conditions with an experienced operator, can provide accurate histological assessment of tissue. The remaining techniques show potential for incorporation into endoscopic equipment and practice, although further component development is needed, followed by robust prospective validation of accuracy. Optical coherence tomography illustrates tissue "texture" well and gives good assessment of mucosal thickness and layers. Multiphoton microscopy produces high-resolution images at a subcellular resolution. Raman spectroscopy and hyperspectral imaging are less developed endoscopically but provide a tissue "fingerprint" which can distinguish between tissue types. Molecular imaging may become a powerful adjunct to other techniques, with its ability to precisely label specific molecules within tissue and thereby enhance imaging.
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Affiliation(s)
- Ben Glover
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Julian Teare
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Nisha Patel
- Department of Surgery and Cancer, Imperial College London, London, UK
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24
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He H, Stylogiannis A, Afshari P, Wiedemann T, Steiger K, Buehler A, Zakian C, Ntziachristos V. Capsule optoacoustic endoscopy for esophageal imaging. JOURNAL OF BIOPHOTONICS 2019; 12:e201800439. [PMID: 31034135 PMCID: PMC7065619 DOI: 10.1002/jbio.201800439] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 04/25/2019] [Accepted: 04/26/2019] [Indexed: 05/03/2023]
Abstract
Detection and monitoring of esophageal cancer severity require an imaging technique sensitive enough to detect early pathological changes in the esophagus and capable of analyzing the esophagus over 360 °in a non-invasive manner. Optoacoustic endoscopy (COE) has been shown to resolve superficial vascular structure of the esophageal lumen in rats and rabbits using catheter-type probes. Although these systems can work well in small animals, they are unsuitable for larger lumens with thicker walls as required for human esophageal screening, due to their lack of position stability along the full organ circumference, sub-optimal acoustic coupling and limited signal-to-noise ratio (SNR). In this work, we introduce a novel capsule COE system that provides high-quality 360° images of the entire lumen, specifically designed for typical dimensions of human esophagus. The pill-shaped encapsulated probe consists of a novel and highly sensitive ultrasound transducer fitted with an integrated miniature pre-amplifier, which increases SNR of 10 dB by minimizing artifacts during signal transmission compared to the configuration without the preamplifier. The scanner rotates helically around the central axis of the probe to capture three-dimensional images with uniform quality. We demonstrate for the first time ex vivo volumetric vascular network images to a depth of 2 mm in swine esophageal lining using COE. Vascular information can be resolved within the mucosa and submucosa layers as confirmed by histology of samples stained with hematoxylin and eosin and with antibody against vascular marker CD31. COE creates new opportunities for optoacoustic screening of esophageal cancer in humans.
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Affiliation(s)
- Hailong He
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
| | - Antonios Stylogiannis
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
| | - Parastoo Afshari
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
| | - Tobias Wiedemann
- Institute for Diabetes and CancerHelmholtz Zentrum MünchenNeuherbergGermany
| | - Katja Steiger
- Department of PathologyKlinikum Rechts der Isar, Technical University of MunichMunichGermany
| | - Andreas Buehler
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
| | - Christian Zakian
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
| | - Vasilis Ntziachristos
- Institute of Biological and Medical ImagingHelmholtz Zentrum MünchenNeuherbergGermany
- Chair of Biological Imaging and TranslaTUMTechnische Universität MünchenMunichGermany
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25
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Cannizzaro R, Maiero S, Fornasarig M, Canzonieri V, Magris R, Guarnieri G, Urbani M, Buonadonna A, Baresic T, Spessotto P. Probe-based confocal laser endomicroscopy (pCLE) is a suitable method for extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) evaluation. Onco Targets Ther 2019; 12:4577-4583. [PMID: 31354291 PMCID: PMC6590055 DOI: 10.2147/ott.s198034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 03/18/2019] [Indexed: 11/30/2022] Open
Abstract
The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.
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Affiliation(s)
- Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Stefania Maiero
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Mara Fornasarig
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Vincenzo Canzonieri
- Pathology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Raffaella Magris
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Giovanni Guarnieri
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Martina Urbani
- Oncologic Radiation Therapy and Diagnostic Imaging, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Angela Buonadonna
- Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Tanja Baresic
- Nuclear Medicine, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Paola Spessotto
- Molecular Oncology, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
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26
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Capuano A, Andreuzzi E, Pivetta E, Doliana R, Favero A, Canzonieri V, Maiero S, Fornasarig M, Magris R, Cannizzaro R, Mongiat M, Spessotto P. The Probe Based Confocal Laser Endomicroscopy (pCLE) in Locally Advanced Gastric Cancer: A Powerful Technique for Real-Time Analysis of Vasculature. Front Oncol 2019; 9:513. [PMID: 31263680 PMCID: PMC6584847 DOI: 10.3389/fonc.2019.00513] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 05/29/2019] [Indexed: 12/24/2022] Open
Abstract
Probe based confocal laser endomicroscopy (pCLE) is an advanced technique which provides imaging of gastrointestinal mucosa at subcellular resolution and, importantly, a valid tool for the evaluation of microvasculature during endoscopic examination. In order to assess intratumoral vascularization and the efficiency of blood flow in locally advanced gastric cancer, we examined 57 patients through pCLE imaging. The vascular alterations in gastric cancer were mainly characterized by leakage and by the presence of tortuous and large size vessels. Defects in blood flow were detected very rarely. No association between the angiogenic score and the gastric tumor site or histological type was observed. Interestingly, no correlation was also found with the tumor grading indicating that the vascular angiogenic anomalies in gastric cancer represent an early pathological event to be observed and detected. The majority of patients displayed unchanged vascular alterations following neoadjuvant chemotherapy and this positively correlated with stable or progressive disease, suggesting that an unaltered angiogenic score could per se be indicative of poor therapeutic efficacy. Different vascular parameters were evaluated by immunofluorescence using bioptic samples and the vessel density did not correlate with clinical staging, site or histologic type. Interestingly, only CD105, Multimerin-2 and GLUT1 were able to discriminate normal from tumoral gastric mucosa. Taken together, these findings indicate that functional and structural angiogenic parameters characteristic of tumor blood network were fully detectable by pCLE. Moreover, the evaluation of tumor vasculature by real-time assessment may provide useful information to achieve tailored therapeutic interventions for gastric cancer patients.
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Affiliation(s)
- Alessandra Capuano
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Eva Andreuzzi
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Eliana Pivetta
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Roberto Doliana
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Andrea Favero
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | | | - Stefania Maiero
- Oncological Gastroenterology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Mara Fornasarig
- Oncological Gastroenterology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Raffaella Magris
- Oncological Gastroenterology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Maurizio Mongiat
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
| | - Paola Spessotto
- Molecular Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy
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27
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Cassese G, Amendola A, Maione F, Giglio MC, Pagano G, Milone M, Aprea G, Luglio G, De Palma GD. Serrated Lesions of the Colon-Rectum: A Focus on New Diagnostic Tools and Current Management. Gastroenterol Res Pract 2019; 2019:9179718. [PMID: 30774654 PMCID: PMC6350577 DOI: 10.1155/2019/9179718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 12/23/2018] [Indexed: 02/07/2023] Open
Abstract
Prompt diagnosis and correct management of the so called "serrated lesions" (SLs) of the colon-rectum are generally considered of crucial importance in the past years, mainly due to their histological heterogeneity and peculiar clinical and molecular patterns; sometimes, they are missed at conventional endoscopy and are possibly implicated in the genesis of interval cancers. The aim of this review is to focus on the diagnostic challenges of serrated lesions, underlying the role of both conventional endoscopy and novel technologies. We will show how an accurate and precise diagnosis should immediately prompt the most appropriate therapy other than defining a proper follow-up program. It will be emphasized how novel endoscopic techniques may provide better visualization of mucosal microsurface structures other than enhancing the microvascular architecture, in order to better define and characterize specific patterns of mucosal lesions of the gastrointestinal tract. Standard therapy of SLs of the colon-rectum is still very debated, also due to the relatively lack of studies focusing on treatment issues. The high risk of incomplete resection, together with the high rate of postcolonoscopy interval cancers, suggests the need of an extra care when facing this kind of lesions. Given this background, we will outline useful technical tips and tricks in the resection of SLs, taking aspects such as the size and location of the lesions, as well as novel available techniques and technologies, other than future perspectives, including confocal laser endomicroscopy into consideration. Follow-up of SLs is another hot topic, also considering that their clinical impact has been misunderstood for a long time. The incidence of the so called interval colorectal cancer underlines how some weaknesses exist in current screening and follow-up programs. Considering the lack of wide consensus for the management of some SLs, we will try to summarize and clarify the best strategies for their optimal management.
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Affiliation(s)
- Gianluca Cassese
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Alfonso Amendola
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Francesco Maione
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Mariano Cesare Giglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gianluca Pagano
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Marco Milone
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Aprea
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Gaetano Luglio
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
| | - Giovanni Domenico De Palma
- University of Naples “Federico II”, Department of Clinical Medicine and Surgery, Italy
- Center of Excellence for Technological Innovation in Surgery, University of Naples “Federico II”, Italy
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28
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Li T, Hui H, Hu C, Ma H, Yang X, Tian J. Multiscale imaging of colitis in mice using confocal laser endomicroscopy, light-sheet fluorescence microscopy, and magnetic resonance imaging. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-8. [PMID: 30701723 PMCID: PMC6985686 DOI: 10.1117/1.jbo.24.1.016003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 01/15/2019] [Indexed: 06/09/2023]
Abstract
The objective of our study is to develop a multimodality approach by combining magnetic resonance imaging (MRI) and optical imaging methods to assess acute murine colitis at the macro- and microscopic level. In vivo MRI is used to measure the cross-sectional areas of colons at the macroscopic level. Dual-color confocal laser endomicroscopy (CLE) allows in vivo examination of the fluorescently labeled epithelial cells and microvessels in the mucosa with a spatial resolution of ∼1.4 μm during ongoing endoscopy. To further validate the structural changes of the colons in three-dimensions, ex vivo light-sheet fluorescence microscopy (LSFM) is applied for in-toto imaging of cleared colon sections. MRI, LSFM, and CLE findings are significantly correlated with histological scoring (p < 0.01) and the inflammation-associated activity index (p < 0.01). Our multimodality imaging technique permits visualization of mucosa in colitis at different scales, which can enhance our understanding of the pathogenesis of inflammatory bowel diseases.
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Affiliation(s)
- Tianmeng Li
- Northeastern University, Sino-Dutch Biomedical and Information Engineering School, Shenyang, China
- Chinese Academy of Sciences, Institute of Automation, CAS Key Laboratory of Molecular Imaging, Beijing, China
- Institute of Automation, Beijing Key Laboratory of Molecular Imaging, Beijing, China
| | - Hui Hui
- Chinese Academy of Sciences, Institute of Automation, CAS Key Laboratory of Molecular Imaging, Beijing, China
- Institute of Automation, Beijing Key Laboratory of Molecular Imaging, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Chaoen Hu
- Chinese Academy of Sciences, Institute of Automation, CAS Key Laboratory of Molecular Imaging, Beijing, China
- Institute of Automation, Beijing Key Laboratory of Molecular Imaging, Beijing, China
| | - He Ma
- Northeastern University, Sino-Dutch Biomedical and Information Engineering School, Shenyang, China
| | - Xin Yang
- Chinese Academy of Sciences, Institute of Automation, CAS Key Laboratory of Molecular Imaging, Beijing, China
- Institute of Automation, Beijing Key Laboratory of Molecular Imaging, Beijing, China
| | - Jie Tian
- Chinese Academy of Sciences, Institute of Automation, CAS Key Laboratory of Molecular Imaging, Beijing, China
- Institute of Automation, Beijing Key Laboratory of Molecular Imaging, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
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29
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Confocal laser microscopy as novel approach for real-time and in-vivo tissue examination during minimal-invasive surgery in colon cancer. Surg Endosc 2018; 33:1811-1817. [DOI: 10.1007/s00464-018-6457-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 09/18/2018] [Indexed: 01/01/2023]
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30
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Diagnosis of Superficial Gastric Lesions Together with Six Gastric Lymphoma Cases via Probe-Based Confocal Laser Endomicroscopy: A Retrospective Observational Study. Gastroenterol Res Pract 2018; 2018:5073182. [PMID: 30008745 PMCID: PMC6020488 DOI: 10.1155/2018/5073182] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 04/16/2018] [Indexed: 02/07/2023] Open
Abstract
Objective To evaluate the performance of probe-based confocal laser endomicroscopy (pCLE) in diagnosis of gastric lesions. Methods An outpatient department- (OPD-) based retrospective study was conducted for patients with suspected upper gastrointestinal (GI) tract lesions who underwent pCLE between 2014 and 2016 at a tertiary hospital in China. Final diagnosis was based on the histopathological reports. CLE reports were compared to histopathological reports to evaluate the diagnostic ability, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy. Results 322 of 380 patients were diagnosed with gastric lesions via pCLE, including inflammation and benign ulcers (n = 110), atrophy and intestinal metaplasia (n = 152), intraepithelial neoplasia (n = 27), adenocarcinoma (n = 27), and lymphoma (n = 6). In total, the diagnostic ability of CLE in evaluation of gastric lesions showed sensitivity 72.4% (95% confidence interval (CI): 67.1-77.2%); specificity 93.1% (95% CI: 5.6-8.4%); PPV 72.4% (95% CI: 67.1-77.2%); NPV 93.1% (95% CI: 5.6-8.4%); and accuracy 88.9% (95% CI: 87.3-90.4%), respectively. We further observed the capability of pCLE in diagnosing six gastric lymphoma showing those affected mucosa densely infiltrated with identical and round-shaped abnormal cells. Immunohistochemistry analysis confirmed one patient with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) and five with mucosa-associated lymphoid tissue (MALT) lymphoma. Conclusion pCLE is an accurate tool for the detection of gastric lesions and shows optimal values of sensitivity and negative predictivity. Moreover, combining pCLE with white light endoscopy (WLE) may be a promising adjunct to conventional biopsy sampling in evaluating GI tract with suspected lymphoma.
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31
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He H, Buehler A, Bozhko D, Jian X, Cui Y, Ntziachristos V. Importance of Ultrawide Bandwidth for Optoacoustic Esophagus Imaging. IEEE TRANSACTIONS ON MEDICAL IMAGING 2018; 37:1162-1167. [PMID: 29727279 DOI: 10.1109/tmi.2017.2777891] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Optoacoustic (photoacoustic) endoscopy has shown potential to reveal complementary contrast to optical endoscopy methods, indicating clinical relevance. However operational parameters for accurate optoacoustic endoscopy must be specified for optimal performance. Recent support from the EU Horizon 2020 program ESOTRAC to develop a next-generation optoacoustic esophageal endoscope directs the interrogation of the optimal frequency required for accurate implementation. We simulated the frequency response of the esophagus wall and then validated the simulation results with experimental measurements of pig esophagus. Phantoms and fresh pig esophagus samples were measured using two detectors with central frequencies of 15 or 50 MHz, and the imaging performance of both detectors was compared. We analyzed the frequency bandwidth of optoacoustic signals in relation to morphological layer structures of the esophagus and found the 50 MHz detector to differentiate layer structures better than the 15 MHz detector. Furthermore, we identify the necessary detection bandwidth for visualizing esophagus morphology and selecting ultrasound transducers for future optoacoustic endoscopy of the esophagus.
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Spessotto P, Fornasarig M, Pivetta E, Maiero S, Magris R, Mongiat M, Canzonieri V, De Paoli P, De Paoli A, Buonadonna A, Serraino D, Panato C, Belluco C, Cannizzaro R. Probe-based confocal laser endomicroscopy for in vivo evaluation of the tumor vasculature in gastric and rectal carcinomas. Sci Rep 2017; 7:9819. [PMID: 28852161 PMCID: PMC5575283 DOI: 10.1038/s41598-017-10963-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 08/17/2017] [Indexed: 12/17/2022] Open
Abstract
Probe-based Confocal Laser Endomicroscopy (pCLE) is a powerful imaging technique that allows to perform gastrointestinal endomicroscopy at subcellular resolution. The aim of this study was to assess the use of pCLE to evaluate tumor angiogenesis in rectal and gastric cancers. A total of 35 consecutive patients with gastric and 91 with rectal carcinomas underwent endoscopy and pCLE during the same examination. Vascular assessment was based on vessel shape and size, vessel permeability and blood flow, and allowed the creation of an angiogenic score ranging from 0, for normal vasculature, to 4, for aberrant vasculature. A significant difference for the presence of vessels with large diameter and defective blood flow was found between rectal and gastric cancers. Overall, rectal cancers displayed a higher angiogenic score compared to gastric cancers. Conventional therapy induced a striking reduction in the angiogenic score only in rectal cancer patients. Taken together, our findings suggest that the pCLE technology is suitable for the evaluation of the tumor microvasculature abnormalities. Therefore, the real-time assessment of the vasculature status may represent a promising approach to predict the efficacy of the treatments and improve the clinical management of patients with gastric or rectal carcinomas.
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Affiliation(s)
- Paola Spessotto
- Molecular Oncology, Department of Translational Research, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Mara Fornasarig
- Gastroenterology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Eliana Pivetta
- Molecular Oncology, Department of Translational Research, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Stefania Maiero
- Gastroenterology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Raffaella Magris
- Gastroenterology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Maurizio Mongiat
- Molecular Oncology, Department of Translational Research, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | | | - Paolo De Paoli
- Scientific Directorate, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Antonino De Paoli
- Radiation Oncology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Angela Buonadonna
- Medical Oncology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Diego Serraino
- Epidemiology and Biostatistics, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Chiara Panato
- Epidemiology and Biostatistics, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Claudio Belluco
- Surgical Oncology, CRO-IRCCS, National Cancer Institute, Aviano, Italy
| | - Renato Cannizzaro
- Gastroenterology, CRO-IRCCS, National Cancer Institute, Aviano, Italy.
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Maione F, Giglio MC, Luglio G, Rispo A, D'Armiento M, Manzo B, Cassese G, Schettino P, Gennarelli N, Siciliano S, D'Armiento FP, De Palma GD. Confocal laser endomicroscopy in ulcerative colitis: beyond endoscopic assessment of disease activity. Tech Coloproctol 2017; 21:531-540. [PMID: 28674950 DOI: 10.1007/s10151-017-1654-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 02/25/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim of this study was to investigate the role of confocal laser endomicroscopy (CLE) in the assessment of disease activity in ulcerative colitis (UC). METHODS Consecutive patients with UC referred to our inflammatory bowel disease unit for colonoscopy were enrolled. Patients without UC were used as controls. UC activity was evaluated by white light endoscopy and classified according to the Mayo Ulcerative Colitis Endoscopic Score of Severity. Endoscopic biopsies were also taken for histological assessment of disease activity and then assessed with CLE. Three parameters were evaluated; crypt architecture (crypt diameter, inter-crypt distance, presence of fused crypts, crypts regularity), microvascular pattern (regular, dilated, irregular and deformed), fluorescein leakage. RESULTS Fifty patients with UC and 10 controls were enrolled. At colonoscopy, 11 patients (22%), 19 patients (38%), 12 patients (24%) and 8 patients (16%) presented a Mayo score of 0, 1, 2 and 3, respectively. At CLE, fused crypts were present in all the patients with UC and absent in controls. Crypt diameter and inter-crypt distance showed a parallel increase with the Mayo score. Fluorescein leakage and irregular vessels were more frequently found in case of a high level of endoscopic severity, but were also identified in about 20% of UC patients with normal mucosa. Biopsies also demonstrated the presence of histological activity in 4 patients with endoscopically inactive colitis. CONCLUSIONS CLE might be a useful tool to determine inflammatory activity in UC. Fused crypts appeared to be a CLE marker of UC, while other abnormalities, like microvascular alteration and fluorescein leakage, have also been identified in patients with mucosal healing at endoscopy. Larger series are required to validate these results and the advantages of a CLE-based assessment of UC activity.
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Affiliation(s)
- F Maione
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - M C Giglio
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G Luglio
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - A Rispo
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - M D'Armiento
- Department of Advanced Biomedical Sciences, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - B Manzo
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G Cassese
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - P Schettino
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - N Gennarelli
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - S Siciliano
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - F P D'Armiento
- Department of Advanced Biomedical Sciences, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - G D De Palma
- Department of Clinical Medicine and Surgery, School of Medicine, Univesity of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
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Tan WK, di Pietro M, Fitzgerald RC. Past, present and future of Barrett's oesophagus. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2017; 43:1148-1160. [PMID: 28256346 PMCID: PMC6839968 DOI: 10.1016/j.ejso.2017.02.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 02/06/2017] [Accepted: 02/06/2017] [Indexed: 02/08/2023]
Abstract
Barrett's oesophagus is a condition which predisposes towards development of oesophageal adenocarcinoma, a highly lethal tumour which has been increasing in incidence in the Western world over the past three decades. There have been tremendous advances in the field of Barrett's oesophagus, not only in diagnostic modalities, but also in therapeutic strategies available to treat this premalignant disease. In this review, we discuss the past, present and future of Barrett's oesophagus. We describe the historical and new evolving diagnostic criteria of Barrett's oesophagus, while also comparing and contrasting the British Society of Gastroenterology guidelines, American College of Gastroenterology guidelines and International Benign Barrett's and CAncer Taskforce (BOBCAT) for Barrett's oesophagus. Advances in endoscopic modalities such as confocal and volumetric laser endomicroscopy, and a non-endoscopic sampling device, the Cytosponge, are described which could aid in identification of Barrett's oesophagus. With regards to therapy we review the evidence for the utility of endoscopic mucosal resection and radiofrequency ablation when coupled with better characterization of dysplasia. These endoscopic advances have transformed the management of Barrett's oesophagus from a primarily surgical disease into an endoscopically managed condition.
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Affiliation(s)
- W K Tan
- MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom
| | - M di Pietro
- MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom
| | - R C Fitzgerald
- MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom.
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Bertani H, Palazzo L, Mirante VG, Pigò F. Confocal Laser Endomicroscopy in GI Tract. DIAGNOSIS AND ENDOSCOPIC MANAGEMENT OF DIGESTIVE DISEASES 2017:1-20. [DOI: 10.1007/978-3-319-42358-6_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Ellebrecht DB, Gebhard MPE, Horn M, Keck T, Kleemann M. Laparoscopic Confocal Laser Microscopy Without Fluorescent Injection. Surg Innov 2016; 23:341-6. [DOI: 10.1177/1553350616637690] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Introduction. Histological analysis of surgical specimen is the gold standard for cancer classification. In particular, frozen histological diagnosis of vague peritoneal spots or uncertain excision of tumors plays a crucial role for proceeding with or without change of the operation procedure. Confocal laser microscopy (CLM) enables in vivo and real-time high-resolution tissue analysis. To evaluate a novel technique of CLM without any fluorescent dye, this pilot ex vivo study demonstrates a CLM camera device for minimal invasive surgical approach. Methods. In 5 cases, a laparoscopic CLM camera was used for examining colon and rectum specimen. Images of nonmalignant and malignant intestinal mucosa were characterized in terms of specific signal-patterns. No fluorescent dye was used. Correlations to findings in conventional histology were systematically recorded and described. Results. Using this CLM camera device, it is possible to analyze colon specimen mucosa. Nonmalignant and malignant intestinal mucosa show specific signal patterns. Nonmalignant mucosa is defined by honeycomb structure. There is deregulated structure in colon and rectum carcinoma mucosa. The inside lumen is irregular. The radial border appears swollen with reduced contrast. Discussion. This pilot study shows that the assessment of colon mucosa with a prototype of CLM camera for minimally invasive surgical approach without any fluorescent dye is feasible. It is possible to differentiate between benign and malignant mucosa in colon specimen by easy to evaluate and reproducible parameters. These first steps of this pioneering achievement to establish CLM in minimal invasive surgical procedures show a great potential for a more reliable intraoperative evaluation of suspect foci.
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Affiliation(s)
- David B. Ellebrecht
- University Medical Centre Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | | | - Marco Horn
- University Medical Centre Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Tobias Keck
- University Medical Centre Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Markus Kleemann
- University Medical Centre Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
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Vargas G, Vincent KL, Wei J, Bourne N, Motamedi M. Topical injury evaluation of the murine colorectal mucosa using confocal endomicrosopy: a valuable method for assessing mucosal injuries associated with risk of pathogen transmission. J Microsc 2016; 264:227-237. [PMID: 27351717 DOI: 10.1111/jmi.12438] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 05/03/2016] [Accepted: 05/30/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Concern regarding the effect of epithelial damage to the colorectal surface and possible impact on sexually transmitted infection transmission prompts the need for methods to evaluate the mucosal microscopic surface in preclinical studies examining such injury. This includes determining the effect of topical HIV prevention products on mucosal barrier integrity. In vivo imaging with high-resolution endomicroscopy could reveal defects in the mucosal barrier resulting from injury/surface trauma. METHODS Confocal endomicroscopy was investigated to assess the ability to image surface injury resulting from topical application of a chemical used in lubricants and microbial products. Mice treated with a 50 μL rectal dose of 0.2% benzalkonium chloride solution, 1% benzalkonium chloride or phosphate-buffered saline control for 20 min were imaged in vivo using confocal endomicroscopy for assessment of epithelial disruption. Following imaging, mice were sacrificed and rectal tissue evaluated by histology. Confocal images were graded based on degree of disruption to crypt and epithelial microstructure. Histology was graded based on percent of epithelial disruption observed in stained sections. Confocal image features were confirmed by high-resolution two-photon microscopy. RESULTS Based on quantitative grading of in vivo confocal endomicroscopy images, disruption at the microscopic scale was observed following treatment with benzalkonium chloride, with increased injury occurring with higher dose. Epithelial disruption at the lumen surface, evident between crypts and alteration in crypt structure on the luminal side were observed in confocal endomicroscopy and confirmed by histology. CONCLUSIONS High-resolution imaging by confocal endomicroscopy can be used as a noninvasive tool for rapid visual assessment of rectal epithelial integrity following surface injury, potentially providing valuable indication of epithelial injury or trauma.
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Affiliation(s)
- Gracie Vargas
- Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, U.S.A.. .,Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, U.S.A..
| | - Kathleen Listiak Vincent
- Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, U.S.A.,Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, U.S.A
| | - Jingna Wei
- Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, U.S.A
| | - Nigel Bourne
- Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, U.S.A.,Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, U.S.A
| | - Massoud Motamedi
- Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, U.S.A.,Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, U.S.A
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Prieto SP, Lai KK, Laryea JA, Mizell JS, Muldoon TJ. Quantitative analysis of ex vivo colorectal epithelium using an automated feature extraction algorithm for microendoscopy image data. J Med Imaging (Bellingham) 2016; 3:024502. [PMID: 27335893 DOI: 10.1117/1.jmi.3.2.024502] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 04/28/2016] [Indexed: 12/20/2022] Open
Abstract
Qualitative screening for colorectal polyps via fiber bundle microendoscopy imaging has shown promising results, with studies reporting high rates of sensitivity and specificity, as well as low interobserver variability with trained clinicians. A quantitative image quality control and image feature extraction algorithm (QFEA) was designed to lessen the burden of training and provide objective data for improved clinical efficacy of this method. After a quantitative image quality control step, QFEA extracts field-of-view area, crypt area, crypt circularity, and crypt number per image. To develop and validate this QFEA, a training set of microendoscopy images was collected from freshly resected porcine colon epithelium. The algorithm was then further validated on ex vivo image data collected from eight human subjects, selected from clinically normal appearing regions distant from grossly visible tumor in surgically resected colorectal tissue. QFEA has proven flexible in application to both mosaics and individual images, and its automated crypt detection sensitivity ranges from 71 to 94% despite intensity and contrast variation within the field of view. It also demonstrates the ability to detect and quantify differences in grossly normal regions among different subjects, suggesting the potential efficacy of this approach in detecting occult regions of dysplasia.
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Affiliation(s)
- Sandra P Prieto
- University of Arkansas , Department of Biomedical Engineering, 1 University Boulevard, Fayetteville, Arkansas 72701, United States
| | - Keith K Lai
- University of Arkansas for Medical Sciences , Department of Pathology, 4301 West Markham Street, Little Rock, Arkansas 72205, United States
| | - Jonathan A Laryea
- University of Arkansas for Medical Sciences , Department of Gastrointestinal Surgery, 4301 West Markham Street, Little Rock, Arkansas 72205, United States
| | - Jason S Mizell
- University of Arkansas for Medical Sciences , Department of Gastrointestinal Surgery, 4301 West Markham Street, Little Rock, Arkansas 72205, United States
| | - Timothy J Muldoon
- University of Arkansas , Department of Biomedical Engineering, 1 University Boulevard, Fayetteville, Arkansas 72701, United States
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Chang J, Ip M, Yang M, Wong B, Power T, Lin L, Xuan W, Phan TG, Leong RW. The learning curve, interobserver, and intraobserver agreement of endoscopic confocal laser endomicroscopy in the assessment of mucosal barrier defects. Gastrointest Endosc 2016; 83:785-91.e1. [PMID: 26344879 DOI: 10.1016/j.gie.2015.08.045] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 08/26/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Confocal laser endomicroscopy can dynamically assess intestinal mucosal barrier defects and increased intestinal permeability (IP). These are functional features that do not have corresponding appearance on histopathology. As such, previous pathology training may not be beneficial in learning these dynamic features. This study aims to evaluate the diagnostic accuracy, learning curve, inter- and intraobserver agreement for identifying features of increased IP in experienced and inexperienced analysts and pathologists. METHODS A total of 180 endoscopic confocal laser endomicroscopy (Pentax EC-3870FK; Pentax, Tokyo, Japan) images of the terminal ileum, subdivided into 6 sets of 30 were evaluated by 6 experienced analysts, 13 inexperienced analysts, and 2 pathologists, after a 30-minute teaching session. Cell-junction enhancement, fluorescein leak, and cell dropout were used to represent increased IP and were either present or absent in each image. For each image, the diagnostic accuracy, confidence, and quality were assessed. RESULTS Diagnostic accuracy was significantly higher for experienced analysts compared with inexperienced analysts from the first set (96.7% vs 83.1%, P < .001) to the third set (95% vs 89.7, P = .127). No differences in accuracy were noted between inexperienced analysts and pathologists. Confidence (odds ratio, 8.71; 95% confidence interval, 5.58-13.57) and good image quality (odds ratio, 1.58; 95% confidence interval, 1.22-2.03) were associated with improved interpretation. Interobserver agreement κ values were high and improved with experience (experienced analysts, 0.83; inexperienced analysts, 0.73; and pathologists, 0.62). Intraobserver agreement was >0.86 for experienced observers. CONCLUSION Features representative of increased IP can be rapidly learned with high inter- and intraobserver agreement. Confidence and image quality were significant predictors of accurate interpretation. Previous pathology training did not have an effect on learning.
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Affiliation(s)
- Jeff Chang
- Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Matthew Ip
- Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Michael Yang
- Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Brendon Wong
- Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Theresa Power
- Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia; Faculty of Medicine, The University of Notre Dame, Sydney, New South Wales, Australia
| | - Lisa Lin
- Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia; Faculty of Medicine, The University of Notre Dame, Sydney, New South Wales, Australia
| | - Wei Xuan
- Ingham Institute of Applied Medical Research, Sydney, New South Wales, Australia
| | - Tri Giang Phan
- Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Immunology Division, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Bankstown Hospital, Sydney South West Local Health District, Sydney, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Immunology Division, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia
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Fugazza A, Gaiani F, Carra MC, Brunetti F, Lévy M, Sobhani I, Azoulay D, Catena F, de'Angelis GL, de'Angelis N. Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:4638683. [PMID: 26989684 PMCID: PMC4773527 DOI: 10.1155/2016/4638683] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2015] [Accepted: 12/31/2015] [Indexed: 12/15/2022]
Abstract
Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.
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Affiliation(s)
- Alessandro Fugazza
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Federica Gaiani
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | | | - Francesco Brunetti
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Michaël Lévy
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Iradj Sobhani
- Department of Gastroenterology and Digestive Endoscopy, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
| | - Daniel Azoulay
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
| | - Fausto Catena
- Emergency Surgery Department, University of Parma, 43100 Parma, Italy
| | - Gian Luigi de'Angelis
- Unit of Gastroenterology and Digestive Endoscopy, University of Parma, 43100 Parma, Italy
| | - Nicola de'Angelis
- Unit of Digestive, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Henri Mondor Hospital, AP-HP, 94010 Créteil, France
- Cancer Research Lab. EC2M3, Université Paris-Est, Val de Marne UPEC, 94010 Créteil, France
- Department of Advanced Biomedical Sciences, University Federico II of Naples, 80138 Naples, Italy
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De Palma GD, Maione F, Esposito D, Luglio G, Giglio MC, Siciliano S, Gennarelli N, Cassese G, Campione S, D'Armiento FP, Bucci L. In vivo assessment of tumour angiogenesis in colorectal cancer: the role of confocal laser endomicroscopy. Colorectal Dis 2016; 18:O66-O73. [PMID: 26589643 DOI: 10.1111/codi.13222] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 10/08/2015] [Indexed: 12/13/2022]
Abstract
AIM Tumour neoangiogenesis is a key factor in tumour progression and metastatic spread and the possibility to assess tumour angiogenesis might provide prognostic information. The aim of this study was to establish the role of probe-based confocal laser endomicroscopy (p-CLE) in the identification of vascular architecture and specific morphological patterns in normal colorectal mucosa and malignant lesions during routine endoscopy. METHOD Fourteen consecutive patients with colorectal cancer were included. The following features were identified and then compared between normal and neoplastic mucosa on p-CLE images: vessel shape (straight vs irregular) vessel diameter the 'branching patterns' vessel permeability (fluorescein leakage) and blood flow (normal vs defective flux). Immunohistochemistry was used to confirm the presence and to study the morphology of vascular structures (CD-34 staining) and 'neo-vessels' (WT-1 staining) on tumour and normal mucosal sections. RESULTS Tumour vessels appeared as irregular, ectatic and with a highly variable calibre and branching patterns on p-CLE images. The mean diameter of tumour vessels was significantly larger than those in normal mucosa (weighted mean difference 3.38, 95% CI 2.65-4.11, P = 0.01). Similarly, 'vessel branching' (OR 2.74, 95% CI 1.23-6.14, P = 0.01), fluorescent dye 'extravasation' (OR 3.46, 95% CI 1.39-8.57, P = 0.01) were significantly more frequent in colorectal cancer than in normal colorectal mucosa. Immunohistochemistry corroborated the p-CLE findings, showing higher vascularity in tumour sections due to neoformed vessels, presenting irregular patterns. CONCLUSION Probe-based confocal laser endomicroscopy provides a noninvasive characterization of the microvascular architecture of colonic mucosa. Different morphological patterns have been described, discriminating normal and malignant microvascular networks in colorectal mucosa.
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Affiliation(s)
- G D De Palma
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - F Maione
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - D Esposito
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - G Luglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - M C Giglio
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - S Siciliano
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - N Gennarelli
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - G Cassese
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
| | - S Campione
- Department of Advanced Biomedical Sciences, University of Naples Federico II, School of Medicine, Naples, Italy
| | - F P D'Armiento
- Department of Advanced Biomedical Sciences, University of Naples Federico II, School of Medicine, Naples, Italy
| | - L Bucci
- Department of Clinical Medicine and Surgery, University of Naples Federico II, School of Medicine, Naples, Italy
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Yang L, Wang J, Tian G, Yuan J, Liu Q, Fu L. Five-lens, easy-to-implement miniature objective for a fluorescence confocal microendoscope. OPTICS EXPRESS 2016; 24:473-84. [PMID: 26832278 DOI: 10.1364/oe.24.000473] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
A fluorescence confocal microendoscope requires a high-performance miniature objective. We present a miniature objective comprising four glass lenses and one plastic aspheric lens. The 0.5 NA objective is achromatized in the wavelength range of 488-550 nm, has a field of view (FOV) of 360 μm, and an outer diameter of 2.6 mm. The assembled miniature objective can resolve features separated by as little as 0.78 μm. The imaging quality of the fluorescence confocal microendoscope with the miniature objective is similar to that of a commercial confocal microscope. It can resolve cellular structures such as crypt structures and epithelial cells.
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43
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Liu D, Zhao X, Zeng X, Dan H, Chen Q. Non-Invasive Techniques for Detection and Diagnosis of Oral Potentially Malignant Disorders. TOHOKU J EXP MED 2016; 238:165-77. [PMID: 26888696 DOI: 10.1620/tjem.238.165] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Dongjuan Liu
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University
| | - Xin Zhao
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University
| | - Xin Zeng
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University
| | - Hongxia Dan
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University
| | - Qianming Chen
- State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University
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44
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Sturm MB, Wang TD. Emerging optical methods for surveillance of Barrett's oesophagus. Gut 2015; 64:1816-23. [PMID: 25975605 PMCID: PMC5019028 DOI: 10.1136/gutjnl-2013-306706] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 04/17/2015] [Indexed: 12/20/2022]
Abstract
The rapid rise in incidence of oesophageal adenocarcinoma has motivated the need for improved methods for surveillance of Barrett's oesophagus. Early neoplasia is flat in morphology and patchy in distribution and is difficult to detect with conventional white light endoscopy (WLE). Light offers numerous advantages for rapidly visualising the oesophagus, and advanced optical methods are being developed for wide-field and cross-sectional imaging to guide tissue biopsy and stage early neoplasia, respectively. We review key features of these promising methods and address their potential to improve detection of Barrett's neoplasia. The clinical performance of key advanced imaging technologies is reviewed, including (1) wide-field methods, such as high-definition WLE, chromoendoscopy, narrow-band imaging, autofluorescence and trimodal imaging and (2) cross-sectional techniques, such as optical coherence tomography, optical frequency domain imaging and confocal laser endomicroscopy. Some of these instruments are being adapted for molecular imaging to detect specific biological targets that are overexpressed in Barrett's neoplasia. Gene expression profiles are being used to identify early targets that appear before morphological changes can be visualised with white light. These targets are detected in vivo using exogenous probes, such as lectins, peptides, antibodies, affibodies and activatable enzymes that are labelled with fluorescence dyes to produce high contrast images. This emerging approach has potential to provide a 'red flag' to identify regions of premalignant mucosa, outline disease margins and guide therapy based on the underlying molecular mechanisms of cancer progression.
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Affiliation(s)
- Matthew B Sturm
- Division of Gastroenterology Departments of Medicine, Biomedical Engineering, Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA,Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Thomas D Wang
- Division of Gastroenterology Departments of Medicine, Biomedical Engineering, Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA,Departments of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA,Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA
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45
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Singh A, Chak A. Advances in the management of Barrett's esophagus and early esophageal adenocarcinoma. Gastroenterol Rep (Oxf) 2015; 3:303-15. [PMID: 26486568 PMCID: PMC4650977 DOI: 10.1093/gastro/gov048] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2015] [Accepted: 08/24/2015] [Indexed: 12/17/2022] Open
Abstract
The incidence of esophageal adenocarcinoma (EAC) has markedly increased in the United States over the last few decades. Barrett’s esophagus (BE) is the most significant known risk factor for this malignancy. Theoretically, screening and treating early BE should help prevent EAC but the exact incidence of BE and its progression to EAC is not entirely known and cost-effectiveness studies for Barrett’s screening are lacking. Over the last few years, there have been major advances in our understanding of the epidemiology, pathogenesis and endoscopic management of BE. These developments focus on early recognition of advanced histology and endoscopic treatment of high-grade dysplasia. Advanced resection techniques now enable us to endoscopically treat early esophageal cancer. In this review, we will discuss these recent advances in diagnosis and treatment of Barrett’s esophagus and early esophageal adenocarcinoma.
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Affiliation(s)
- Ajaypal Singh
- Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Cleveland, OH, USA
| | - Amitabh Chak
- Division of Gastroenterology and Hepatology, University Hospitals Case Medical Center, Cleveland, OH, USA
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46
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Vanneste BGL, Van De Voorde L, de Ridder RJ, Van Limbergen EJ, Lambin P, van Lin EN. Chronic radiation proctitis: tricks to prevent and treat. Int J Colorectal Dis 2015; 30:1293-303. [PMID: 26198994 PMCID: PMC4575375 DOI: 10.1007/s00384-015-2289-4] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/13/2015] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The purpose of this study was to give an overview of the measures used to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the treatment of CRP. METHODS Medical literature databases including PubMed and Medline were screened and critically analyzed for relevance in the scope of our purpose. RESULTS CRP is a relatively frequent late side effect (5-20%) and mainly dependent on the dose and volume of irradiated rectum. Radiation treatment (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT and intensity-modulated RT. Also, newer techniques like protons and new devices such as rectum spacers and balloons have been developed to spare rectal structures. Biopsies do not contribute to diagnosing CRP and should be avoided because of the risk of severe rectal wall damage, such as necrosis and fistulas. There is no consensus on the optimal treatment of CRP. A variety of possibilities is available and includes topical and oral agents, hyperbaric oxygen therapy, and endoscopic interventions. CONCLUSIONS CRP has a natural history of improving over time, even without treatment. This is important to take into account when considering these treatments: first be conservative (topical and oral agents) and be aware that invasive treatments can be very toxic.
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Affiliation(s)
- Ben G L Vanneste
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands.
| | - Lien Van De Voorde
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Rogier J de Ridder
- Department of Gastroenterology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Evert J Van Limbergen
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Philippe Lambin
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
| | - Emile N van Lin
- Department of Radiation Oncology (MAASTRO Clinic), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 3035, 6202 NA, Maastricht, The Netherlands
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Moore C, Mehta V, Ma X, Chaudhery S, Shi R, Moore-Medlin T, Lian T, Nathan CAO. Interobserver agreement of confocal laser endomicroscopy for detection of head and neck neoplasia. Laryngoscope 2015; 126:632-7. [DOI: 10.1002/lary.25646] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2015] [Indexed: 01/17/2023]
Affiliation(s)
- Charles Moore
- Louisiana State University Health Shreveport School of Medicine; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Vikas Mehta
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Xiaohui Ma
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Shabnum Chaudhery
- Louisiana State University Health Shreveport School of Medicine; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Department of Pathology; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Runhua Shi
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Tara Moore-Medlin
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Timothy Lian
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
| | - Cherie-Ann O. Nathan
- Department of Otolaryngology-Head and Neck Surgery; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
- Feist-Weiller Cancer Center; Louisiana State University Health Shreveport; Shreveport Louisiana U.S.A
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Ieni A, Barresi V, Todaro P, Caruso RA, Tuccari G. Cell-block procedure in endoscopic ultrasound-guided-fine-needle-aspiration of gastrointestinal solid neoplastic lesions. World J Gastrointest Endosc 2015; 7:1014-1022. [PMID: 26322154 PMCID: PMC4549658 DOI: 10.4253/wjge.v7.i11.1014] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Revised: 07/01/2015] [Accepted: 08/03/2015] [Indexed: 02/05/2023] Open
Abstract
In the present review we have analyzed the clinical applications of endoscopic ultrasound-guided-fine-needle-aspiration (EUS-FNA) and the methodological aspects obtained by cell-block procedure (CBP) in the diagnostic approach to the gastrointestinal neoplastic pathology. CBP showed numerous advantages in comparison to the cytologic routine smears; in particular, better preservation of cell architecture, achievement of routine haematoxylin-eosin staining equivalent to histological slides and possibility to perform immunohistochemistry or molecular analyses represented the most evident reasons to choose this method. Moreover, by this approach, the differential diagnosis of solid gastrointestinal neoplasias may be more easily achieved and the background of contaminant non-neoplastic gastrointestinal avoided. Finally, biological samples collected by EUS-FNA CBP-assisted should be investigated in order to identify and quantify further potential molecular markers.
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49
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Ciocâlteu A, Pirici D, Stefanescu A, Georgescu CV, Şurlin V, Săftoiu A. Endomicroscopy with Fluorescent CD105 Antibodies for "In Vivo" Imaging of Colorectal Cancer Angiogenesis. CURRENT HEALTH SCIENCES JOURNAL 2015; 41:288-292. [PMID: 30538832 PMCID: PMC6246985 DOI: 10.12865/chsj.41.03.17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 03/15/2015] [Indexed: 11/25/2022]
Abstract
The aim of this case report was to evaluate the feasibility of in vivo acquisition of microscopic images using fluorescent CD105 antibodies for molecular imaging in human colorectal cancer. After excluding the presence of tissue autofluorescence, the antibody solution was topically administered through a spray-catheter. The targeted area was analyzed by eCLE and images were recorded. The fractal dimension of tumor vessels and the vessel density were determined using ImageJ software. Immunohistochemistry was used as a gold standard. In vivo CLE analysis of CD105 expression enabled the study of tumor vascular network, revealing a chaotic structure.
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Affiliation(s)
- A Ciocâlteu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Romania
| | - D Pirici
- Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Romania
| | - A Stefanescu
- Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Romania
| | - C V Georgescu
- Department of Pathology, Emergency County Hospital, Craiova, Romania
| | - V Şurlin
- Department of Surgery, University of Medicine and Pharmacy of Craiova, Romania
| | - A Săftoiu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Romania
- Endoscopy Department, Copenhagen University Hospital Herlev, Copenhagen, Denmark
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50
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WU JP, WALTON M, WANG A, ANDERSON P, WANG T, KIRK T, ZHENG M. The development of confocal arthroscopy as optical histology for rotator cuff tendinopathy. J Microsc 2015; 259:269-75. [DOI: 10.1111/jmi.12260] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 03/26/2015] [Indexed: 01/26/2023]
Affiliation(s)
- J.-P. WU
- Department of Mechanical Engineering; Curtin University; Perth Australia
| | - M. WALTON
- Wrightington Hospital; Upper Limb Unit; Wigan UK
| | - A. WANG
- School of Surgery; University of Western Australia; Perth Australia
| | | | - T. WANG
- School of Surgery; University of Western Australia; Perth Australia
| | - T.B. KIRK
- Department of Mechanical Engineering; Curtin University; Perth Australia
| | - M.H. ZHENG
- School of Surgery; University of Western Australia; Perth Australia
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