The Probe Based Confocal Laser Endomicroscopy (pCLE) in Locally Advanced Gastric Cancer: A Powerful Technique for Real–Time Analysis of Vasculature

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.

BCAT1 Activates PI3K/AKT/mTOR Pathway and Contributes to the Angiogenesis and Tumorigenicity of Gastric Cancer

“…Thus, controlling tumor angiogenesis is a promising therapeutic strategy for limiting tumor progression ( Weis and Cheresh, 2011 ). A wide evidence demonstrates that GC is a highly angiogenic cancer ( Chakroborty et al, 2004 ; Capuano et al, 2019 ); thus, focusing on antiangiogenesis may provide promising choices for GC treatment.…”

pCLE highlights distinctive vascular patterns in early gastric cancer and in gastric diseases with high risk of malignant complications

“…In our study, we were able to detect vascular changes even in non-lesion areas using pCLE, supporting the evidence that vascular changes may indicate a favorable microenvironment for carcinogenesis. We found that the mucosal vasculature of EGC patients was also characterized by vessel tortuosity, but in contrast to the regular organization observed in atrophic gastritis, these vessels often appeared patchy, as is also the case in neoplastic gastric tissue 20 . This peculiar aspect of vessel tortuosity was also found, in part, in atrophic metaplastic autoimmune gastritis.…”

“…Capillary diameter increased significantly in chronic gastritis with or without atrophy, but since the difference from normal gastric mucosa was too small, the authors felt that it was difficult to distinguish this change under real-time procedures. Recently, we thoroughly investigated the vascular features of locally advanced GC by evaluating the use of pCLE for the analysis of intratumoral angiogenesis, and we demonstrated that the functional and structural angiogenic parameters of the tumor blood network were fully detectable with this innovative endoscopic technique 20 . In this study, we provide evidence for the potential of this technique to assess vascular characteristics in gastric disease with malignant complications.…”

“…Particular patterns of vascular changes are described that identify specific categories of patients with ECG or with disease at high risk for developing GC. The use of pCLE provided evidence that locally advanced GC is characterized by a remarkably abnormal and nonfunctional vasculature, regardless of tumor stage, location, and histological type 20 , suggesting that the vascular network may be a critical factor in establishing a compliant tumor microenvironment for this type of cancer, even in the early stages of tumor development. The formation of aberrant vasculature could favor or even precede lesions with malignant complications or higher GC risk and, together with other molecular and functional alterations of the microenvironment, profoundly influence cancer cell proliferation and migration as well as tumor progression 31 , 32 .…”

Diagnostic accuracy of probe-based confocal laser endomicroscopy and tissue sampling by endoscopic retrograde cholangiopancreatography in indeterminate biliary strictures: a meta‑analysis

“…The pCLE enables low-energy laser light to be focused and illuminated through its inner small hole to produce a tissue image, which improves the accuracy of targeted biopsy and realizes instant optical biopsy 4 . The pCLE has been used to assess the histopathology of the gastrointestinal tract in vivo 5 , 6 . The accuracy of pCLE in the diagnosis of gastrointestinal tumors has been demonstrated in previous studies 7 , 8 .…”