Study protocol for a multicenter randomized controlled trial to compare radiofrequency ablation with surgical resection for treatment of pancreatic insulinoma

Background: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. Aims: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. Methods: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. Discussion: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure. & COPY; 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

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

Efficacy and Safety of Endoscopic Ultrasound-Guided Radiofrequency Ablation for Pancreatic Neuroendocrine Tumors: A Systematic Review and Metanalysis

: Introduction: The development of dedicated endoscopes and the technical evolution of endoscopic ultrasound (EUS) have allowed a direct approach to pancreatic neoplastic lesions both for diagnosis and treatment. Among the more promising targets are pancreatic neuroendocrine tumors (Pan-NETs). Aim: to describe the evolution of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) with particular attention to the treatment of PanNETs, focusing on safety and clinical efficacy of the technique. Methods: MEDLINE, Scopus, and Cochrane Library databases were searched for studies reporting about EUS-RFA for the treatment of PanNETs. Studies with outcomes of interest were selected and results were reported to describe clinical success, complications, fol-low-ups, and electrodes used. Clinical success was defined as the disappearance of clinical symp-toms for functional (F-) PanNETs and as complete ablation per nonfunctional (NF)-PanNETs. The pooled data were analyzed by a random-effects model. Results: Nineteen studies were selected, including 183 patients (82 males, 44.8%) with 196 lesions (101 F-PanNETs and 95 NF-PanNETs). Pooled estimates for the overall AE rates for the clinical efficacy were 17.8% (95% CI 9.1-26.4%) and 95.1% (95% CI 91.2-98.9%) for F-PanNETs and 24.6% (95% CI 7.4-41.8%) and 93.4% (95% CI 88.4-98.4%) for NF-PanNETs. Conclusions: EUS-RFA appears to be a mini-invasive technique with a good safety and efficacy profile for the treatment of F- and NF-PanNETs. EUS-RFA could be of-fered as possible alternative to surgery for the treatment of low-grade NF- or F-PanNETs, especially for those patients that are not eligible or are at high-risk for surgery

The Role of EUS-Guided FNA and FNB in Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is an increasingly recognized disease classified into two different subtypes based on histology. According to the International Diagnostic Criteria (ICDC), the diagnosis is achieved using a combination of different criteria. In patients presenting with a typical imaging appearance, the diagnosis may be straightforward, and steroid treatment is recommended, even without histological confirmation. In patients with atypical imaging or mass-forming appearance, the differential diagnosis with pancreatic cancer is challenging and crucial for treatment strategy. Endoscopic ultrasound (EUS)-guided tissue acquisition has been proposed to achieve a histological diagnosis. Fine-needle aspiration (FNA) was first proposed to aspirate cells from pancreatic lesions. Despite excellent results in terms of sensitivity for pancreatic cancer, the data are disappointing regarding the diagnosis of AIP. The recent development of new needles allowing fine-needle biopsy (FNB) has been associated with improved diagnostic accuracy based on preserving the tissue architecture, which is necessary to detect the typical histological features of AIP. However, the published literature on the role of EUS-guided FNA and FNB is limited and mainly focused on type 1 AIP. The present study aimed to review the available literature on the role of EUS-guided FNA and FNB in the diagnosis of AIP

Risk Models for Pancreatic Cyst Diagnosis

: The overall prevalence of pancreatic cysts (PCs) is high in the general population. In clinical practice PCs are often incidentally discovered and are classified into benign, premalignant, and malignant lesions according to the World Health Organization. For this reason, in the absence of reliable biomarkers, to date clinical decision-making relies mostly on risk models based on morphological features. The aim of this narrative review is to present the current knowledge regarding PC's morphologic features with related estimated risk of malignancy and discuss available diagnostic tools to minimize clinically relevant diagnostic errors

Contrast-Enhanced Harmonic Endoscopic Ultrasound-Guided Fine-Needle Aspiration versus Standard Fine-Needle Aspiration in Pancreatic Masses: A Propensity Score Analysis

Background: Whether endoscopic ultrasound (EUS) contrast-enhanced fine-needle aspiration (CH-EUS-FNA) determines superior results in comparison to standard EUS-FNA in tissue acquisition of pancreatic masses remains unclear. The aim of this study was to compare these two techniques on a series of patients with solid pancreatic lesions. Methods: 362 patients underwent EUS-FNA (2008–2019), after the propensity score matching of two groups were compared; 103 treated with CH-EUS-FNA (group 1) and 103 with standard EUS-FNA (group 2). The primary outcome was the diagnostic accuracy. Secondary outcomes were sensitivity, specificity, and sample adequacy. Results: Diagnostic sensitivity was 87.6% in group 1 and 80% in group 2 (p = 0.18). The negative predictive value was 56% in group 1 and 41.5% in group 2 (p = 0.06). The specificity and positive predictive values were 100% for both groups. Diagnostic accuracy was 89.3% and 82.5%, respectively (p = 0.40). Sample adequacy was 94.1% in group 1 and 91.2% in group 2 (p = 0.42). The rate of adequate core histologic samples was 33% and 28.1%, respectively (p = 0.44), and the number of needle passes to obtain adequate samples were 2.4 ± 0.6 and 2.7 ± 0.8, respectively (p = 0.76). These findings were confirmed in subgroup analyses, conducted according to lesion size and contrast enhancement pattern. Conclusions: CH-EUS-FNA does not appear to be superior to standard EUS-FNA in patients with pancreatic masses