Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Neovascularization, Pathologic

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Cancer

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Chrysarobin

Consecutive patients with gastric cancer will be examined using magnification endoscopy with narrow band imaging and probe based confocal laser endomicroscopy.

Consecutive patients with colorectal cancer will be examined using magnification endoscopy with narrow band imaging and probe based confocal laser endomicroscopy.

Magnification endoscopy with narrow band imaging is an optically enhanced endoscopic imaging technique used for better characterization of lesions as compared to white light endoscopy alone. With only a push of a button optical filters are applied to reduce the illuminating light to 415 nm (blue) and 540 nm (green) wavelengths, which are selectively absorbed by haemoglobin. As a result the superficial vascular networks are highlighted and morphological changes in capillary patterns can be described for different gastrointestinal lesions.

Magnification endoscopy with narrow band imaging

Confocal laser endomicroscopy enables in vivo microscopic analysis during ongoing endoscopy and has shown good accuracy for predicting the histopathological diagnosis in lesions of both the upper and lower GI tract. During the examination fluorescein is administered intravenously as a contrast agent, highlighting the vessels and surrounding epithelial structures. The probe based confocal laser endomicroscopy system can be easily integrated into the imaging protocol as it uses flexible catheter probes that can be passed through the working channels of the endoscopes once the area of interest has been identified.

Probe based confocal laser endomicroscopy

Dan I. Gheonea, Assoc. Prof.

Tatiana Cârțână, MD, PhD

The aim of the project is to study the role of minimally invasive imaging methods, such as magnification endoscopy with narrow-band imaging (M-NBI) combined with confocal laser endomicroscopy (CLE), in correlation with immunohistochemical analysis, for assessing the angiogenesis status of patients with gastrointestinal tumors, in particular with colorectal and gastric cancer. Angiogenesis, i.e. the process of forming new blood vessels, represents an essential event for tumor growth and metastasis and the importance of its understanding stems from potential applications for diagnosis, prognosis stratification and mainly from the possibility of developing and improving targeted therapies. While current methods for evaluating tumor vascularity are based on immunohistochemistry techniques with microvascular density (MVD) calculations, these imply repeated tissue sampling and are not feasible in the context of clinical practice. Imaging techniques might overcome limitations associated with MDV measuring, obtaining both functional and morphological information and enabling repeated evaluations that are necessary for the assessment of a dynamic process as angiogenesis during follow-up of targeted therapies.

NBI is a digitally enhanced endoscopic imaging technique that uses optical filters to illuminate tissue with light at blue and green wavelengths. These are selectively absorbed by hemoglobin and, as a result superficial vascular networks are highlighted and morphological changes in capillary patterns can be described for different lesions. CLE represents a revolutionary technology that enables endoscopists to collect real-time in vivo histological images or "virtual biopsies" of the gastrointestinal mucosa during endoscopy, and has raised significant interest for the potential clinical applications and numerous research possibilities. After intravenous administration of fluorescein as a contrast agent, CLE enables real-time visualization of the tumor vasculature, which is structurally and functionally altered compared to the normal vascular networks. Therefore M-NBI will be used for enhanced visualization of morphological changes of the superficial capillaries, while CLE will be directed towards vascular regions of interest for characterization of these changes at the microscopic level. Furthermore, imaging studies will be backed by MVD calculation using immunohistochemical methods, based on tissue samples harvested during endoscopic procedures.

The key objectives of the project are:

* Real-time imaging of angiogenesis in GI tumors by using minimally invasive methods:

  * Endoscopic magnification with narrow-band imaging (M-NBI) for macroscopic assessment of the vascular pattern
  * In vivo probe-based confocal laser endomicroscopy (pCLE) for characterization of the microvascular pattern
* Offline analysis of M-NBI and pCLE sequences with additional image processing software
* Immunohistochemical evaluation of angiogenesis in GI cancers based on MVD calculation
* Comparing imaging (M-NBI and pCLE) and pathological (immunohistochemistry) data using computer aided diagnosis (CAD) The study will include patients with gastric (n=20) and colorectal (n=30) cancers that will be prospectively evaluated according to the predefined protocols.

Magnification endoscopy with narrow band imaging (M-NBI) will be performed for each patient after the identification of the lesion with conventional white light endoscopy. With only a push of a button optical filters are applied to reduce the illuminating light to 415 nm (blue) and 540 nm (green) wavelengths for enhanced visualization of capillary changes. Classification of the vascular pattern will be made on-site by the examiner (DIR) and multiple images will be saved for off-site later analysis. While interpretation of endoscopic images can be subjective and operator-dependent we will also perform an objective evaluation with computer-aided analysis based on image processing software. A vascular region of interest will be selected in NBI mode for targeted microscopic examination with pCLE and tissue sampling for pathology and IHC assessment. M-NBI examination will also be performed for normal mucosa for comparative analysis of the vascular pattern.

Confocal laser endomicroscopy (CLE) will be performed for visualization and characterization of vascular changes inside the tumor, using the probe-based CLE system (pCLE). The faster image acquisition rate of the pCLE system (12 frames per second) enables direct in vivo visualization of blood flow. The main advantage of the pCLE system is that it can be easily integrated into the imaging protocol as its flexible catheter probes can be passed through the working channels of the endoscopes once the vascular area of interest is selected with M-NBI. For pCLE examinations we will use fluorescein as a contrast agent which is already approved for in vivo human examinations. Fluorescein is administered intravenously, highlighting the vessels and surrounding epithelial structures. The vascular pattern will be assessed in real-time as well as off-site based on objective measurements of the stored sequences that will include different vascular parameters (vessel diameter, vascular density). These will be determined for both tumor tissue and normal adjacent mucosa as control, using dedicated software.

Immunohistochemistry (IHC) analysis with MVD calculations will be assessed and correlated to the imaging findings. Paired biopsies of tumors and normal GI mucosa obtained during endoscopic procedures (ensuring co-registration with M-NBI and pCLE examined regions) will be processed for fixation in 10% neutral buffered formalin (NBF), paraffin embedding and sectioning. For MVD analysis, the blocks will be completely cut in serial sections 4-25 μm-thick, with one thick section for every 10 thin sections. In order to assess the total vascular architecture we will utilize non-selective endothelial cell markers, such as anti-CD31 and anti-CD34 antibodies.

Novel Endoscopic Imaging Methods for the Evaluation of Blood Vessels in Gastrointestinal Cancers

Study of Minimally Invasive Endoscopic IMaging Methods for the Evaluation of neoANGiogenesis in Gastrointestinal Cancers

After identification of the lesion with conventional white light endoscopy, endoscopic magnification with narrow-band imaging (M-NBI) will be performed for enhanced visualization of the capillary changes. A vascular region of interest will be selected in the M-NBI mode for targeted microscopic examination with probe based confocal laser endomicroscopy (pCLE) and tissue sampling for pathology and immunohistochemistry assessment. The vascular pattern will be assessed in real-time by the examiner as well as off-site based on objective measurements of the stored sequences that will include different vascular parameters (vessel diameter, vascular density). These will be determined for both tumors and normal adjacent mucosa as control, using dedicated image processing software.

Paired biopsies of GI tumors and normal mucosa obtained during endoscopic procedures (ensuring co-registration with M-NBI and pCLE examined areas) will be processed for immunohistochemical analysis by utilizing anti-CD31 and anti-CD34 antibodies as endothelial cell markers. Microvascular density (MVD) calculations will be performed by using the 'hot-spot' method and the results will be compared to the vascular parameters as assessed from M-NBI and pCLE stored images.

University of Medicine and Pharmacy Craiova

Respiratory Tract (Lung and Bronchial) Diseases

Pleural Diseases

Pleural Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Every patient referred for medical thoracoscopy will be screened. The pCLE of the pleura will be performed 2 times. First, just before the thoracoscopy, through the Boutin's needle or the thoracentesis catheter and second through the working chanel of the pleuroscope. This last acquisition allows visual control to target the pleural endomicroscopy assessment. These two acquisitions will be compared between each other and with the histological samples of the pleuroscopy.

Probe based confocal laser endomicroscopy of the pleura

Duysinx Bernard, PhD

Recently, probe based confocal laser endomicroscopy showed to be able to distinguish malignant from benign pleura during medical thoracoscopy. However The clinical usefulness of this new tool remains to be determined.

The investigators believe that pCLE could be part of mini invasive pleural disease management and could be used during thoracentesis in order to increase the diagnostic yield of this procedure. The investigators are starting a prospective trial to recruit patients referred for medical thoracoscopy to the endoscopy unit.

First, the pCLE probe will be introduced through the Boutin's needle or the thoracentesis catheter, just before the thoracoscopy, in order to investigate the pleural pCLE features and to identify or exclude malignant infiltration. Second those features will be compared to the pCLE acquisition obtained during the medical thoracoscopy (the probe is introduced through the working chanel of the thoracoscope), under visual control. In order to compare the invasive and mini invasive acquisition, 10 criteria will be prospectively assessed.Third, These features will be compared to the histological samples performed during thoracoscopy. Finally, the interpretation of different investigators will be compared.

The 10 criteria are presented below:

1. Abnormal tissular architecture

   No: Correct identification of the previously described normal pleura characteristics Yes: identification of cellular/tissular structures which are not known to correspond to normal pleura (cellular clusters or dark clumps, glands, cells cordons, dysmorphic cells, papillar distribution....)
2. Cellular homogeneity is size, shape and fluorescence, as subjectively assessed by the investigator

   yes no
3. Mean cellular size:

   Small: \< 10µm Moderate: 10 - 20µm Large: \> 20µm
4. Cellular density (with reference to the Chia seed sign)

   Low (lower than the Chia seed sign) Moderate High
5. Dysplastic vessels:

   Yes: (vascular leaks, tortuous or giant vessels) No: no dysplasia
6. Vascular density (on a full optical area)

   Low: 0 -2 vessels Moderate: 3 - 4 vessels High: \> 4 vessels
7. Organized or anarchic connective fibers

   Anarchic: coarse fibers, irregular in shape, without well-defined architecture Organized : regular in shape and direction, well defined architecture.
8. Chia seed sign on a full optical areal

yes No

Mini Invasive Endomicroscopy of the Pleura for Malignancies Diagnosis

Mini Invasive Probe Based Confocal Laser Endomicroscopy of the Pleura for Malignancies Diagnosis

Before medical thoracoscopy, the pCLE probe will be introduced through the Boutin's needle or the thoracentesis catheter. The pleural pCLE acquisition will be assessed by two experienced and unblinded clinicians (aware of the medical history of the patient) during the procedure. A second acquisition and assessment of the criteria is performed thereafter during the medical thoracoscopy. 10 preselected criteria are used to assess the pCLE acquisition. They are the same than previously published (Bonhomme et al respirology 2020). A third blinded (not aware of the medical history of the patient) investigator will revise the pCLE acquisition (not the same day) to perform the same assessment.

The pCLE features assessed during the mini invasive procedure will be compared to the assessment performed during the thoracoscopy. This assessment will be performed by the blinded investigator. The investigator will not know wether the pCLE acquisition is from mini invasive or invasive procedure for his assessment. The 10 criteria assessed during mini invasive or invasive pleural assessment will be compared to determine their reproducibility. The results will be presented for each criteria as the proportion of concordance between mini and invasive assessment.

The assessment of the 10 criteria will be compared between the different investigators in order to determine the reproducibility of the investigation. The results will be presented for each criteria as the proportion of concordance between mini and invasive assessment.

Every (Serious)adverse event will be reported during the intervention or during post intervention surveillance (1 hour post intervention).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Novel Endoscopic Imaging Methods for the Evaluation of Blood Vessels in Gastrointestinal Cancers	NCT02672774	Gastric Cancer Colorectal Canc... Gastrointestina...	Magnification e... Probe based con...	18 Years - 90 Years	University of Medicine and Pharmacy Craiova
Mini Invasive Endomicroscopy of the Pleura for Malignancies Diagnosis	NCT04731129	Pleural Disease... Pleural Neoplas...	Probe based con...	18 Years -	University of Liege
Mini Invasive Endomicroscopy of the Pleura for Malignancies Diagnosis	NCT04731129	Pleural Disease... Pleural Neoplas...	Probe based con...	18 Years -	University of Liege

Spots Global Cancer Trial Database for probe based confocal laser endomicroscopy