Improving endoscopic ultrasound-guided tissue acquisition of solid and cystic pancreatic lesions

Endoscopic ultrasound (EUS)-guided tissue sampling was introduced in the nineties and offers a minimal invasive and accurate modality for real-time tissue acquisition. Today, its use is continuously growing, with an expanding role of tissue analysis in the era of patient tailored medicine. Although EUS-guided tissue sampling can in-deed provide a tissue diagnosis with a high level of diagnostic accuracy, its outcome strongly depends on the skills and experience of the performer, the sampling tools and techniques, and the way the tissue is handled and processed. Consequently, EUS-guided tissue sampling has been subject to numerous innovations. Adjusting and improving the design of EUS-needles has been and still is a major focus of innovation. Traditionally, tissue sampling was performed using fine needle aspiration (FNA) devices, which mainly harvest loose target cells for cytologic evaluation. Unfortunately, its yield depends on rapid on-site tissue evaluation (ROSE) by a dedicated pathologist, which is not generally available in most EUS-centers. Furthermore, cytology is suboptimal for the identification of tumor invasion or the diagnosing and staging of specific diseases that require additional (immuno-histochemical and molecular) testing, such as autoimmune pancreatitis, submucosal or stromal lesions, and neuroendocrine tumors. Fine needle biopsy (FNB) devices were introduced to overcome these limitations by offering the possibility to harvest histologically intact tissue fragments rather than loose target cells. Parallel to these needle design innovations, EUS-sampling techniques evolved, and several techniques can be performed to date. However, there is no convincing evi-dence for the benefit of either technique, or superiority of one over the other. Pancreatic cystic lesions (PCLs) are rising in prevalence consequent to progressive-ly increasing average lifespan, as well as advancements in diagnostic techniques. Additionally, widespread use of imaging technology in clinical practice has resulted in increased detection of PCLs. PCLs are typically discovered as an incidental find-ing, and are diagnosed in up to 15% of patients as a consequence of routine ab-dominal imaging. Once a PCL is discovered, characterization of the lesion is a criti-cal step towards the selection of appropriate management strategies. Although EUS plays a fundamental role in differentiation of PCL subtypes, mor-phological characterization alone is often insufficient to reach a definitive diagnosis. The large overlap in morphological features among various PCL subtypes contrib-utes to the challenges of interpretation. Consequently, reliance on morphological features alone results in high rates of inappropriate surgical resection based on pre-sumptive diagnosis. Moreover, evaluation of cytology samples via microscopy still remains challenging to interpret due to the paucity of cellularity in the cystic fluid. Pathological reports estimate that sensitivity for the differentiation between mucin-ous and non-mucinous cysts may be as low as 54%. Given these barriers, newer devices have been tested and introduced into clinical practice such as confocal laser endomicroscopy [31] and most notably, endoscopic ultrasound-guided through-the-needle biopsy (TTNB) technique [32]. A specialized through-the-needle microforceps device (Moray Microforceps®, US Endoscopy, Mentor, OH, USA) was recently created to carry out EUS-guided biopsy sampling in PCLs. Aims and outline of the thesis This thesis explores if and how technical factors and use of new devices can im-prove the diagnostic outcome of EUS-guided tissue sampling of pancreatic lesions. Part I focuses on the sampling of solid pancreatic lesions. Part II focuses on the implementing tissue acquisition of cystic pancreatic lesions using the novel microforceps biopsy.