Needle-based Confocal Endomicroscopy Examination of Pancreatic Masses

Background Pancreatic cancer is one of the most aggressive gastrointestinal malignancies with mortality rates following closely the incidence rates. The incidence is increasing and the prognosis is grim especially because of late diagnosis and metastatic potential. While surgical treatment is currently the only potential curative intervention, 80-85% of the PC cases are unfortunately detected in late unresectable stages of the disease. In spite of advances in the diagnosis and management of pancreatic cancer less than 5% of patients are alive at five years.

Endoscopic ultrasound (EUS) represents a highly valuable tool in the management of pancreatic cancer patients. As a minimally invasive technique that enables high-resolution imaging of the pancreatic parenchyma and surrounding structures it is considered the method of choice for the detection of clinically suspected pancreatic tumors, with a negative predictive value close to 100%. Its diagnostic sensitivity was shown by previous studies to be superior compared to other imaging techniques, especially in the case of smaller tumors. Additionally EUS enables guided fine needle aspiration (EUS-FNA) which is currently recommended as the firs-line procedure whenever pathological diagnosis is required. However, EUS-FNA as a sampling technique has its drawbacks, mainly represented by the relatively low negative predictive value in diagnosing pancreatic cancer. It thus cannot reliably rule out a diagnosis of malignancy and patients with high clinical suspicion usually need repeated FNA.

Confocal laser endomicroscopy has emerged in recent years as a novel technique that actually enables in vivo microscopic analysis during ongoing endoscopy. Endomicroscopy can be performed either with dedicated (eCLE) or with miniprobe-based systems (pCLE). It is a contrast based technique, the most widely used agent being the intravenously administered fluorescein. The probe-based endomicroscopy system consists of a flexible catheter probe representing a bundle of optical fibers linked to a micro-objective, a laser scanning unit and the control and acquisition software (Cellvizio; Mauna Kea Technology, Paris, France). The flexible confocal miniprobes were specifically designed to be passed through the working channels of standard endoscopes, biliary catheters or cholangioscopes and thus the pCLE system can be easily integrated in any endoscopy unit. The principle of the technique is based on a laser beam of defined wavelength being focused towards the targeted tissue and the recaptured signal is displayed as 'optical biopsies' in a single horizontal plane.

The potential role of CLE has been explored in pathology of both upper and lower gastrointestinal tract, showing good accuracy for predicting the final histopathological diagnosis based on immediate evaluation of tissue and vascular patterns. Recently CLE has gone beyond the superficial luminal indications with the development of a new microprobe, i.e. a flexible probe thin enough that it can be passed through a 19-gauge needle. Thus under EUS guidance solid organs can be accessed for real-time microscopic information. nCLE imaging of abdominal organs has been so far achieved in animal models. The feasibility of the technique was also proved in a clinical study and descriptive criteria for the diagnosis of pancreatic cystic neoplasm were developed from a multicentre trial. However, only a limited number of cases of pancreatic solid masses have been described with nCLE.

Aim The aim of the proposed study is to describe confocal imaging criteria for pancreatic masses, lymph nodes or liver metastases identified during EUS procedures performed for pancreatic cancer staging (EUS-nCLE), while evaluating also the feasibility and safety of nCLE examination. The hypothesis is that EUS-nCLE could allow targeted tissue sampling of pancreatic lesions resulting in more accurate diagnosis. With further validation of the technique real-time pathological diagnosis could be obtained with immediate initiation of the adequate therapy after a single investigation.