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Objectives: Repeated endoscopic ultrasound (EUS)-guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine-needle biopsy (rEUS-FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes., Methods: Consecutive patients undergoing rEUS-FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6-month follow-up, and benign pathology together with ≥12-month follow-up were adopted as gold standards., Results: Among 462 patients, 56.5% were male, with a median age of 68 (59-75) years, malignancy prevalence 77.0%. Tumor size was 26 (20-35) mm. Second-generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS-FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false-negative and 12 false-positive results). On multivariate analysis, rEUS-FNB performed at high-volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10-3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00-1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second-generation FNB needles (OR 5.42; 95% CI 2.30-12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31-7.06; P = 0.009) were independently related to sample adequacy., Conclusion: Repeated EUS-FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high-volume centers improved diagnostic accuracy. The use of second-generation FNB needles significantly improved sample adequacy over standard EUS-FNB needles., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Objective: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS-RFA for pNENs., Methods: The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS-RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I 2 . Pooled estimates and the 95% confidence interval (CI) were calculated using a random-effect model., Results: Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9-99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1-92.8%). The pooled partial response was 11.4% (95% CI 6.2-18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7-97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0-26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2-2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported., Conclusion: Endoscopic ultrasound-guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

BACKGROUND : It is unknown whether there is an advantage to using the wet-suction or slow-pull technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) with new-generation needles. We aimed to compare the performance of each technique in EUS-FNB., Methods: This was a multicenter, randomized, single-blind, crossover trial including patients with solid lesions of ≥ 1 cm. Four needle passes with 22 G fork-tip or Franseen-type needles were performed, alternating the wet-suction and slow-pull techniques in a randomized order. The primary outcome was the histological yield (samples containing an intact piece of tissue of at least 550 μm). Secondary end points were sample quality (tissue integrity and blood contamination), diagnostic accuracy, and adequate tumor fraction., Results: Overall, 210 patients with 146 pancreatic and 64 nonpancreatic lesions were analyzed. A tissue core was retrieved in 150 (71.4 %) and 129 (61.4 %) cases using the wet-suction and the slow-pull techniques, respectively ( P  = 0.03). The mean tissue integrity score was higher using wet suction ( P  = 0.02), as was the blood contamination of samples ( P  < 0.001). In the two subgroups of pancreatic and nonpancreatic lesions, tissue core rate and tissue integrity score were not statistically different using the two techniques, but blood contamination was higher with wet suction. Diagnostic accuracy and tumor fraction did not differ between the two techniques., Conclusion: Overall, the wet-suction technique in EUS-FNB resulted in a higher tissue core procurement rate compared with the slow-pull method. Diagnostic accuracy and the rate of samples with adequate tumor fraction were similar between the two techniques., Competing Interests: S.F. Crinò has received speaker fees from Steris Endoscopy. A. Larghi is a consultant for Pentax and Boston Scientific, and has received a research grant from Medtronic and teaching fee from Taewoong. À. Ginès is a consultant for Cook Endoscopy. R. Di Mitri is a consultant for Boston Scientific. O. Sendino is a consultant for and has received speaker fees from B. Braun. M.C. Conti Bellocchi, F. Inzani, M. Rimbas, A. Lisotti, G. Manfredi, A.Y.B. Teoh, B. Mangiavillano, L. Bernardoni, E. Manfrin, D. Scimeca, E. Unti, A. Carlino, T. Voiosu, R.B. Mateescu, P. Fusaroli, S. Lega, E. Buscarini, L. Pergola, S.M. Chan, L. Lamonaca, G. Fernández-Esparrach, and A. Facciorusso declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Aim: Intraparenchymal lung masses inaccessible through bronchoscopy or endobronchial ultrasound guidance pose a diagnostic challenge. Furthermore, some fragile or hypoxic patients may be poor candidates for transbronchial approaches. Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) offers a potential diagnostic approach to lung cancers adjacent to the esophagus. We aimed to evaluate the feasibility, accuracy, and safety of trans-esophageal EUS-FNA/FNB for tissue sampling of pulmonary nodules., Methods: We retrospectively analyzed data from patients with pulmonary lesions who underwent EUS-FNA/FNB between March 2015 and August 2021 at eight Italian endoscopic referral centers., Results: A total of 47 patients (36 male; mean age 64.47 ± 9.05 years) were included (22 EUS-FNAs and 25 EUS-FNBs). Overall diagnostic accuracy rate was 88.9% (76.3-96.2%). The sensitivity and diagnostic accuracy were superior for EUS FNB sampling versus EUS-FNA (100% vs. 78.73%); P = 0.05, and (100% vs. 78.57%); P = 0.05, respectively. Additionally, sample adequacy was superior for EUS-FNB sampling versus EUS-FNA (100% vs. 78.5%); P = 0.05. Multivariate logistic regression analysis for diagnostic accuracy showed nodule size at the cutoff of 15 mm (OR 2.29, 1.04-5.5, P = 0.05) and use of FNB needle (OR 4.33, 1.05-6.31, P = 0.05) as significant predictors of higher diagnostic accuracy. There were no procedure-related adverse events., Conclusion: This study highlights the efficacy and safety of EUS-FNA/FNB as a minimally invasive procedure for diagnosing and staging peri-esophageal parenchymal lung lesions. The diagnostic yield of EUS-FNB was superior to EUS-FNA., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Evidence is limited on the comparative diagnostic performance of newer end-cutting fine-needle biopsy (FNB) needles for tissue sampling of pancreatic masses. We performed a systematic review with network meta-analysis to compare the diagnostic accuracy of available FNB needles for sampling of solid pancreatic lesions., Methods: A systematic literature review (Medline and Cochrane Database) was conducted for studies evaluating the accuracy of newer FNB needles in adults undergoing EUS-guided sampling of solid pancreatic masses. The primary outcome was diagnostic accuracy. Secondary outcomes were sample adequacy, diagnostic sensitivity, specificity, and adverse event rate. We performed pairwise and network meta-analyses and appraised the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology., Results: Overall, 16 RCTs (1934 patients) were identified. On network meta-analysis, Franseen needles (Acquire; Boston Scientific, Marlborough, Mass, USA) significantly outperformed reverse-bevel needles (risk ratio [RR], 1.21 [95% confidence interval {CI}, 1.05-1.40] for accuracy and 1.31 [95% CI, 1.05-1.22] for adequacy) and FNA needles (RR, 1.21 [95% CI, 1.01-1.25] for accuracy and 1.07 [95% CI, 1.02-1.13] for adequacy). Likewise, the Fork-tip needle (SharkCore; Medtronic, Dublin, Ireland) was significantly superior to the reverse-bevel needle (RR, 1.17 [95% CI, 1.03-1.33] for accuracy and 1.09 [95% CI, 1.02-1.16] for adequacy) and to the FNA needle (RR, 1.09 [95% CI, 1.01-1.19] for accuracy and 1.03 [95% CI, 1.01-1.07] for adequacy). Other comparisons did not achieve statistical significance. As a consequence, Franseen (surface under the cumulative ranking score, .89 for accuracy and .94 for adequacy) and Fork-tip needles (surface under the cumulative ranking score, .76 for accuracy and .73 for adequacy) ranked as the 2 highest-performing FNB needles. When considering different needle sizes, 25-gauge Franseen and 25-gauge Fork-tip needles were not superior to 22-gauge reverse-bevel needles (RR, 1.18 [95% CI, .96-1.46] and 1.04 [95% CI, .62-1.52]). None of the tested needles was significantly superior to the other FNB devices or to FNA needles when rapid onsite cytologic evaluation was available., Conclusions: Franseen and Fork-tip needles, particularly 22-gauge size, showed the highest performance for tissue sampling of pancreatic masses, with low confidence in estimates., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: A direct comparison between endoscopic ultrasound (EUS) fine-needle biopsy (FNB) and current endoscopic biopsy techniques in patients with subepithelial lesions (SELs) is still lacking. Aim of this multicenter study was to compare the diagnostic performance and safety profile between EUS-FNB and bite-on-bite jumbo biopsy., Methods: Out of 416 patients undergoing endoscopic sampling of SELs between 2017 and 2021, after propensity score matching two groups were compared: 120 undergoing EUS-FNB and 120 sampled with bite-on-bite jumbo biopsy. Primary outcome was sample adequacy. Secondary outcomes were diagnostic accuracy, sensitivity, specificity, and adverse events., Results: Median age was 61 years and most patients were male in both groups. Final diagnosis was GIST in 65 patients (54.1%) in the EUS-FNB group and 62 patients in the bite-on-bite biopsy group (51.6%; p = 0.37). Sample adequacy was significantly higher in the EUS-FNB group as compared to the bite-on-bite biopsy group (94.1% versus 77.5%, p<0.001). EUS-FNB outperformed bite-on-bite biopsy also in terms of diagnostic accuracy (89.3% versus 67.1%, p<0.001) and sensitivity (89% vs 64.5%; p<0.001), whereas specificity was 100% in both groups (p = 0.89). These findings were confirmed in subgroup analysis according to SEL location, final diagnosis, and wall layers of the sampled SEL. Adverse event rate was 6.6% in the EUS-FNB group and 30% in the bite-on-bite biopsy group (p<0.001)., Conclusion: EUS-FNB outperforms bite-on-bite biopsy both in terms of diagnostic yield and safety profile., Competing Interests: Conflict of Interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Background: It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies., Aims: We performed a pooled estimate of the incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasia, with a particular focus on the comparison to the general population., Methods: Computerized bibliographic search of main databases was performed through February 2021. The primary endpoint was the pooled incidence of extrapancreatic malignancies in patients with intraductal papillary mucinous neoplasms. Additional outcome was the comparison between intraductal papillary mucinous neoplasia patients and the general population, expressed in terms of standardized incidence ratio along with 95% confidence intervals., Results: Eighteen studies with 8709 patients were included. The pooled rate of metachronous extrapancreatic malignancies was 10 (6-13)/1000 persons-year. No difference was observed according to intraductal papillary mucinous neoplasia histology and sex, whereas a significantly superior incidence of extrapancreatic malignancies was observed in patients with main-duct (36.7%, 25.4%-48%) as compared to branch-duct intraductal papillary mucinous neoplasia (26.2%, 17.6%-34.8%; p = 0.03). Pooled standardized incidence ratio comparing expected rates in the general population was 1.01 (0.79-1.29); no difference was observed concerning rates of metachronous gastric cancer (standardized incidence ratio 1.60, 0.72-3.54) and colorectal cancer (1.29, 0.92-1.18), whereas biliary cancer was observed more frequently in intraductal papillary mucinous neoplasia patients (2.29, 1.07-4.93)., Conclusion: Patients with intraductal papillary mucinous neoplasia harbor an overall rate of extrapancreatic malignancies as high as 27.3%. The rate of metachronous extrapancreatic malignancies is not superior to the general population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: There is increasing evidence to support the efficacy of endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) technique as a means of sampling pancreatic cystic lesions (PCLs). Results provide evidence demonstrating the benefits of this procedure over standard EUS fine-needle aspiration (FNA), thus supporting a push for its widespread implementation in clinical practice. Though this technique has demonstrated advantages, achieving these advantages in clinical practice is contingent upon careful considerations to ensure safety and efficacy., Areas Covered: The purpose of this review is to assess the level of evidence supporting the use of through-the-needle biopsy, revise its main technical and procedural characteristics, and to develop suggested guidelines outlining the safe assimilation of this device in clinical practice., Expert Opinion: EUS-TTNB enables more definitive and accurate diagnosis of PCLs by providing higher-quality histological samples. However, EUS-TTNB is not appropriate for all PCLs. Selection of suitable patients as well as morphology and risk factors of the cystic lesion is a crucial component of achieving the described benefits of this procedure while minimizing risks of adverse effects. Subjects with weak or absent indications for this procedure are susceptible to a range of complications and may even result in fatality.

Background and Aims: Pancreatic cystic neoplasms (PCNs) carry a considerable malignancy risk. Along with main duct dilation, the presence of enhanced mural nodules represents a significant risk factor for malignancy. Several articles assessed the role of contrast-enhanced EUS (CE-EUS) for the identification of malignant features in mural nodules. We evaluate the pooled diagnostic performance of CE-EUS for the identification of high-grade dysplasia or invasive carcinoma among mural nodules in PCNs., Methods: A systematic review (Medline, PubMed, EMBASE) and meta-analysis were conducted. Subgroup analysis was used to assess the usefulness of a dedicated contrast-harmonic (CH-EUS). The primary outcome was pooled sensitivity for identification of high-grade dysplasia or invasive carcinoma., Results: Ten studies (532 patients) were included. Pooled sensitivity of CE-EUS was 88.2% (95% confidence interval [CI], 82.7%-92.5%), specificity 79.1% (95% CI, 74.5%-83.3%), and diagnostic accuracy 89.6% (95% CI, 83.4%-95.8%). Eight studies (320 patients) were conducted using CH-EUS: pooled sensitivity increased to 97.0% (95% CI, 92.5%-99.2%), specificity to 90.4% (95% CI, 85.2%-94.2%), and diagnostic accuracy to 95.6% (95% CI, 92.6%-98.7%). At 42% disease prevalence (pretest probability), a positive CH-EUS increased the disease probability to 88%, whereas a negative test decreased the disease probability to 2%. The number needed to diagnose was 1.5 (95% CI, 1.7-1.3) for CE-EUS and just 1.2 (95% CI, 1.3-1.1) for CH-EUS., Conclusions: This study provided robust evidence on CE-EUS value for the characterization of mural nodules within PCNs. A dedicated contrast-harmonic mode, namely CH-EUS, provided an increased diagnostic yield in the identification and characterization of malignant mural nodules., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: It is still unclear 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. Aim of this meta-analysis was to compare the diagnostic outcomes of these two techniques., Methods: We searched the PubMed/Medline and Embase database through October 2020 and identified 6 studies, of which 2 randomized controlled trials (recruiting 701 patients). We performed pairwise meta-analysis through a random effects model and expressed data as odds ratio (OR) and 95% confidence interval (CI)., Results: Pooled diagnostic sensitivity was 84.6% (95% CI 80.7%-88.6%) with CH-EUS-FNA and 75.3% (67%-83.5%) with EUS-FNA, with evidence of a significant superiority of the former (OR 1.74, 95% CI 1.26-2.40; p < 0.001). Subgroup analysis confirmed the superiority of CH-EUS-FNA over EUS-FNA only in larger lesions. Pooled diagnostic accuracy was 88.8% (85.6%-91.9%) in CH-EUS-FNA group and 83.6% (79.4%-87.8%) in EUS-FNA group (OR 1.52, 1.01-2.31; p = 0.05). Pooled sample adequacy was 95.1% (91.1%-99.1%) with CH-EUS-FNA and 89.4% (81%-97.8%) with EUS-FNA (OR 2.40, 1.38-4.17; p = 0.02)., Conclusion: CH-EUS-FNA seems to be superior to standard EUS-FNA in patients with pancreatic masses. Further trials are needed to confirm these results.

Introduction: After a failed percutaneous ultrasound (US)-guided sampling, it is recommended that endoscopic ultrasound (EUS)-guided tissue acquisition (TA) be performed for non-resectable solid pancreatic lesions according to the European Federation of Societies for Ultrasound in Medicine and Biology. However, the diagnostic performance of EUS-guided TA in this setting is unknown., Methods: We retrospectively analyzed the performance and safety of EUS-guided TA in patients with a previous failed percutaneous biopsy. We also evaluated the diagnostic delays between the percutaneous approach and EUS diagnosis., Results: Over a period of 2 years, 49 patients were identified (29 males, mean age 65 years). The reasons for failure of percutaneous sampling were inadequate samples in 25 (52.1%) cases and lesions that were not visible or targetable in 24 (47.9%) cases. In one case, EUS-guided TA was not performed because of the interposition of a metallic biliary stent. No adverse events were recorded for both the percutaneous and EUS approaches. The median diagnostic delay was 12 days. Overall, the sensitivity and accuracy of EUS-guided TA were 92.7 and 93.7%, respectively. A subgroup analysis examined cases with inadequate samples obtained with the percutaneous approach, and the sensitivity and accuracy of EUS-guided TA were 85.7 and 88%, respectively., Conclusion: EUS-guided TA is safe and accurate for the diagnosis of pancreatic lesions after a previous inconclusive percutaneous approach.

Background: Current imaging modalities are limited in their ability to distinguish pancreatic cancer (PC) from non-neoplastic pancreatic lesions. The diagnostic use of contrast-enhanced endoscopic ultrasonography (CE-EUS) has increased, and its utility has been reported. Recently, contrast-enhanced harmonic EUS (CH-EUS) was reported to facilitate imaging of parenchymal perfusion and microvessels in pancreatobiliary diseases, leading to a high diagnostic accuracy for PC. The present meta-analysis aims to investigate the usefulness of CH-EUS with enhancement pattern for PC diagnosis., Methods: A systematic meta-analysis of all potentially relevant articles identified in PubMed, the Cochrane library, and Medline was carried out. Fixed-effects or random-effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence interval (CI)., Results: The study enrolled 887 patients from nine eligible studies. Pooled estimates of sensitivity and specificity were 93% (95% CI, 0.91-0.95) and 80% (95% CI, 0.75-0.85), respectively. Subgroup analyses were carried out on the main results after excluding two outliers. Area under summary receiver operating characteristics curve was 0.97. No publication bias was found using funnel plots. No significant relationship was found between the diagnostic odds ratios and the characteristics of the studies including continent and contrast agent., Conclusions: This meta-analysis showed that CH-EUS with qualitative analysis of enhancement pattern is useful for the diagnosis of PC, and has high sensitivity and accuracy, regardless of the type of contrast agent used. This modality may provide improved diagnostic accuracy for PC in clinical practice., (© 2018 Japan Gastroenterological Endoscopy Society.)

Background: The prevalence of malignancy in patients with small solid pancreatic lesions is low; however, early diagnosis is crucial for successful treatment of these cases. Therefore, a method to reliably distinguish between benign and malignant small solid pancreatic lesions would be highly desirable. We investigated the role of endoscopic ultrasound (EUS) elastography in this setting., Methods: Patients with solid pancreatic lesions ≤ 15 mm in size and a definite diagnosis were included. Lesion stiffness relative to the surrounding pancreatic parenchyma, as qualitatively assessed and documented at the time of EUS elastography, was retrospectively compared with the final diagnosis obtained by fine-needle aspiration/biopsy or surgical resection., Results: 218 patients were analyzed. The average size of the lesions was 11 ± 3 mm; 23 % were ductal adenocarcinoma, 52 % neuroendocrine tumors, 8 % metastases, and 17 % other entities; 66 % of the lesions were benign. On elastography, 50 % of lesions were stiffer than the surrounding pancreatic parenchyma (stiff lesions) and 50 % were less stiff or of similar stiffness (soft lesions). High stiffness of the lesion had a sensitivity of 84 % (95 % confidence interval 73 % - 91 %), specificity of 67 % (58 % - 74 %), positive predictive value (PPV) of 56 % (50 % - 62 %), and negative predictive value (NPV) of 89 % (83 % - 93 %) for the diagnosis of malignancy. For the diagnosis of pancreatic ductal adenocarcinoma, the sensitivity, specificity, PPV, and NPV were 96 % (87 % - 100 %), 64 % (56 % - 71 %), 45 % (40 % - 50 %), and 98 % (93 % - 100 %), respectively., Conclusions: In patients with small solid pancreatic lesions, EUS elastography can rule out malignancy with a high level of certainty if the lesion appears soft. A stiff lesion can be either benign or malignant., Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of this study was to analyze the outcomes of a long-term intraductal papillary mucinous neoplasm (IPMN) registry and evaluate new guidelines., Methods: A prospectively maintained IPMN registry involving 6 centers in Europe and the United States was used to collect the data. Patients with more than 1-year follow-up and no malignancy diagnosed within the first 3 months of surveillance were included., Results: From 1999 to 2014, 620 patients were included. The median follow-up time was 3 years. Thirty-seven (6%) patients developed malignancy with a median time from IPMN diagnosis to malignancy of 10.3 months. The 1-, 5-, and 10-year actuarial rates of disease-free survival were 97%, 93%, and 92% respectively. Four hundred thirty-one patients met criteria for low-risk branch duct IPMN consisting of cyst size less than 3 cm, with no solid component or main duct dilation. Eight malignancies were diagnosed in this subgroup, all of them within the first 5 years. From this subcohort, 112 patients had a follow-up time of more than 5 years, and no malignancy was diagnosed., Conclusions: In IPMN lesions with low-risk features at baseline, the risk of progression to malignancy after the first 5 years of follow-up was minimal. Furthermore, the main cyst characteristics remained unchanged during their surveillance.

Background and Aims: Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at a late stage. Little is known about the incidental finding of early-stage PDAC. The aim of the current study was to determine the etiology of small solid pancreatic lesions (≤15 mm) to optimize clinical management., Methods: Inclusion criterion for the retrospective study analysis was the incidental finding of primarily undetermined small solid pancreatic lesions ≤15 mm in 394 asymptomatic patients. Final diagnoses were based on histology or cytology obtained by imaging-guided biopsy (and at least 12-month follow-up) and/or surgery. Contrast-enhanced US or contrast-enhanced EUS was performed in 219 patients., Results: The final diagnoses of 394 patients were as follows: 146 PDACs, 156 neuroendocrine tumors, 28 metastases into the pancreas from other primary sites, and 64 various other etiologies. Contrast-enhanced US allowed differential diagnosis of PDAC and non-PDAC in 189 of 219 patients (86%)., Conclusions: Approximately 40% of patients with small solid pancreatic lesions had very early stage PDAC. Approximately 60% of small solid pancreatic lesions ≤15 mm are not PDAC and, therefore, do not require radical surgery. Without preoperative diagnosis, an unacceptably large proportion of patients would be exposed to radical surgery with significant morbidity and mortality., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the literature to put its clinical outcomes in the appropriate perspective., Methods: We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines., Results: Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3)., Conclusions: The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the accuracy of cytology, carcinoembryonic antigen (CEA), and amylase levels in the preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMNs)., Methods: An international registry was started in 2005 and included patients with clinically suspected IPMNs. Those who underwent surgery and had preoperative endoscopic ultrasonography fine-needle aspiration were selected for the study., Results: One hundred eighty patients were included. Cytological analysis for neoplastic cells in IPMNs showed high specificity (87.8%) but low sensitivity (39.4%). The median CEA level was 525.5 ng/mL (n = 78) in IPMNs versus 9.7 ng/mL in nonmucinous cysts (n = 6), showing an area under the receiver operating characteristic curve (AUC) of 0.87. The optimal cutoff CEA value for distinguishing IPMN from nonmucinous cysts was 129 ng/mL. At this level, the sensitivity was 76.9%, and specificity was 83.3%, yielding a positive predictive value of 95.9% and a negative predictive value of 41.9%. Carcinoembryonic antigen was a poor predictor of neoplasia in IPMNs (AUC = 0.55). Amylase did not distinguish IPMNs from mucinous cystadenomas (MCAs) (median, 3759 U/L [n = 28 IPMNs] and 497 U/L [n = 3 MCAs], AUC = 0.65)., Conclusions: Cytology has a limited role because of its lack of sensitivity. Carcinoembryonic antigen modestly differentiated between mucinous and nonmucinous lesions. Amylase did not distinguish IPMNs versus MCAs.

Objectives: To evaluate the potential role of contrast harmonic endoscopic ultrasound (CH-EUS) in the differential diagnosis of pancreatic cysts and detection of malignancy., Methods: Patients who underwent CH-EUS for evaluation of cyst wall, septae, and solid components of pancreatic cysts were included. The findings were compared to fine needle aspiration and surgery., Results: Seventy-six patients were included. Serous and mucinous cysts were both hyperenhanced (86% and 89%, respectively; P = ns), whereas pseudocysts were hypoenhanced in 90% of the cases (P = 0.000004 vs serous cysts and P = 0.000005 vs mucinous cysts). Patients showing hyperenhanced solid components were finally diagnosed with malignancy (2 malignant intraductal papillary mucinous neoplasms, 2 cystic neuroendocrine tumors), in contrast to the patients with nonenhanced solid components who resulted to have either benign cysts with internal mucus clots (n = 10) or pseudocysts with internal debris (n = 8)., Conclusions: CH-EUS allowed differentiation between pseudocysts and other pancreatic cysts but not mucinous versus serous cysts. Malignant vegetations inside pancreatic cystic lesions were clearly shown by CH-EUS as solid components with features of hyperenhancement, directing EUS-fine needle aspiration of potential neoplastic areas and avoiding puncture of debris and mucus plugs.

Background: Intraductal papillary mucinous neoplasms of the pancreas are increasingly diagnosed. Due to their malignant potential, greater understanding of their nature is required., Aims: Define risk factors for malignancy in intraductal papillary mucinous neoplasms., Methods: An international, multicentre study was performed in Europe and the United States. Clinical databases were reviewed for patients with intraductal papillary mucinous neoplasms diagnosis., Results: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed a statistically significant association between cancer/high-grade dysplasia and the variables smoking history (OR 1.9, 95% CI [1.1-3.1]), body mass index (OR 1.1, 95% CI [1-1.1]), symptoms (OR 3.4, 95% CI [1.9-6]), jaundice (OR 0.1, 95% CI [0-0.3]), and steatorrhea (OR 0.3, 95% CI [0.1-0.8]). Univariate analysis showed no association between malignancy and the cyst number/location (p=0.3 and p=0.5, respectively) although a strong association was shown for cyst size (p<0.001). The presence and size of nodules (p<0.01) and main duct involvement (p<0.001) were also strongly related with malignancy., Conclusion: The presence of jaundice and steatorrhea, smoking, high body mass index, and imaging features such as cyst size, main duct involvement, and the presence and size of mural nodules are associated with high-grade neoplasia in intraductal papillary mucinous neoplasms., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Endoscopic ultrasound-guided fine needle aspiration is routinely used in the diagnostic work up of pancreatic cancer but has a low sensitivity. Studies showed that Pancreatic Duodenal Homeobox-1 (PDX-1) is expressed in pancreatic cancer, which is associated with a worse prognosis. We aimed to verify whether the assessment of PDX-1 in endoscopic ultrasound-guided fine needle aspiration samples may be helpful for the diagnosis of pancreatic cancer., Methods: mRNA of 54 pancreatic cancer and 25 cystic lesions was extracted. PDX-1 expression was assessed by Real-Time PCR., Results: In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative. The positivity was associated with a probability of 0.98 (95% CI 0.90-1.00) of having cancer and the negativity with one of 0.08 (95% CI 0.01-0.27). The probability of cancer rose to 1.00 (95% CI 0.97-1.00) for patients positive to both PDX-1 and cytology and fell to 0.0 (95% CI 0.00-0.15) in patients negative for both., Conclusions: PDX-1mRNA is detectable in samples of pancreatic cancer. Its quantification may be helpful to improve the diagnosis of pancreatic cancer., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: The differential diagnosis between primary pancreatic neoplasms versus pancreatic metastases (PM) is challenging. Endoscopic ultrasonography with fine-needle aspiration can be used to differentiate primary versus metastatic tumors although with a suboptimal accuracy. Recently, contrast harmonic EUS (CH-EUS) has been reported as an adjunct in the diagnosis of pancreatic neoplasms. We evaluated the potential role of CH-EUS in the differential diagnosis of PM., Methods: This study is a retrospective analysis of a prospectively maintained database. Of the 266 patients, 4.1% were diagnosed with PM. Endoscopic ultrasonography with fine-needle aspiration and/or surgical pathology represented our criterion standard., Results: The origins of PM were renal cancer (3 patients), colon cancer(2 patients), breast cancer (2 patients), ovarian cancer (1 patient), melanoma(1 patient), lymphoma (1 patient), and sarcoma (1 patient). All lesions appeared hypoechoic at standard EUS. At CH-EUS, of the 11 lesions, 6 appeared hypoenhancing (colon cancer, sarcoma, and breast and ovarian cancer), 4 were hyperenhancing (renal cancer and lymphoma),and 1 was isoenhancing (melanoma)., Conclusions: In our population, standard EUS features of PM were unremarkable. At CH-EUS, most of the PM appeared hypoenhancing suggesting a possible malignant origin. However, a subset of PM showed hyperenhancing pattern. In the appropriate context, particularly when cancer history is present, CH-EUS may add to the differential diagnosis and potentially spare endoscopic ultrasonography with fine-needle aspiration.

Background and Aim: Contrast harmonic endoscopic ultrasound (CH-EUS) was recently introduced to clinical practice; its reproducibility among endosonographers is unknown. Our aim was to assess the interobserver agreement (IA) in CH-EUS., Methods: Fifteen endosonographers (eight experienced and seven non-experienced) from 11 Italian EUS centers evaluated 80 video-cases (40 solid pancreatic lesions, 20 pancreatic cystic lesions and 20 submucosal lesions) of CH-EUS, according to the degree of enhancement, the pattern of distribution and the washout of the contrast agent. IA within each group and between the two groups of observers was assessed with the Fleiss kappa statistic., Results: Overall IA was moderate for the uptake and fair for the pattern of distribution and the washout. In solid pancreatic lesions, IA was moderate for the uptake and fair for the pattern and the washout. In cystic pancreatic lesions, IA was uniformly moderate for the assessment of uptake, slight for the pattern and fair for the washout. In submucosal tumors, IA was substantial for the uptake, slight for the pattern and fair for the washout. Non-experienced endosonographers demonstrated, in most cases, comparable IA with the experienced ones., Conclusions: Interobserver agreement among endosonographers for CH EUS was satisfactory. In particular, overall IA varied from slight to substantial, being fair in the majority of cases. Inherent structural features of the lesions, as well as technical differences between the variables assessed, could have accounted for the fluctuation of the results. Outcomes of IA were reproducible between experienced and non-experienced endosonographers., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background & Aims: Contrast harmonic echo (CHE) has been developed for endoscopic ultrasound (EUS). This new technique detects echo signals from microbubbles in vessels with very slow flow, without artifacts. We assessed whether CHE-EUS increases the accuracy of diagnosis of pancreatic solid lesions., Methods: At a tertiary-care EUS center, we examined 90 patients who were suspected of having pancreatic solid neoplasm. Radial and linear echoendoscopes were used with dedicated software for CHE. Sonovue (Bracco International BV, Amsterdam, The Netherlands) uptake, pattern, and washout were studied; data were compared for pancreatic lesions and adjacent parenchyma. The final diagnosis was obtained based on results of surgical pathology and/or EUS-fine needle aspiration (FNA) analyses., Results: The finding of a hypoenhancing mass with an inhomogeneous pattern was a sensitive and accurate identifier of patients with adenocarcinoma (96% and 82%, respectively) (49 of 51 patients with primary pancreatic adenocarcinoma had a hypoenhancing mass that was inhomogeneous and had fast washout). This finding was more accurate in diagnosis than the finding of a hypoechoic lesion using standard EUS (P < .000). Hyperenhancement specifically excluded adenocarcinoma (98%), although sensitivity was low (39%). Of neuroendocrine tumors, 11 of 13 were non-hypo-enhancing (9 hyperenhancing, 2 isoenhancing). Interestingly, CHE-EUS allowed detection of small lesions in 7 patients who had uncertain standard EUS findings because of biliary stents (n = 5) or chronic pancreatitis (n = 2). Targeted EUS-FNA was performed on these lesions., Conclusions: Detection of a hypoenhancing and inhomogeneous mass accurately identified patients with pancreatic adenocarcinoma. CHE-EUS increased the detection of malignant lesions in difficult cases (patients with chronic pancreatitis or biliary stents) and helped guide EUS-FNA. A hyperenhancing pattern could be used to rule out adenocarcinoma., (Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Biliary stents have been found to interfere with endoscopic ultrasound (EUS) tumor (T) and nodal (N) staging in patients with periampullary cancer. Our aim was to determine whether this also occurs in patients with pancreatic head cancer., Patients and Methods: We studied a consecutive series of patients who were undergoing preoperative EUS for diagnosis and staging of suspected pancreatic cancer, some of whom had biliary stents in situ and some of whom did not. The main end point was the uni- and multivariate association of biliary stenting with T and N mis-staging by EUS. The surgical T and N stages were used as gold standards., Results: A total of 65 patients were identified (19 with biliary stents in situ and 46 without). Surgical stage T4 was found more frequently in patients with stents (53% vs. 22%, P = 0.014). The T stage by EUS was correct in 85% of the patients without biliary stents and in 47% of the patients with stents. The frequency of mis-staging by EUS was significant only among patients with a biliary stent. The distribution by EUS N stage did not differ significantly from the surgical N-stage distribution in the two groups of patients. According to the multivariate analysis, patients with stents were 6.55 times more likely to be incorrectly T staged (95% confidence interval [CI] 1.69-25.49) and 3.71 times more likely to be incorrectly N staged (95% CI 1.11-12.45) than patients without stents., Conclusions: The results add support to the recommendation that EUS staging of pancreatic head neoplasms should be performed prior to stent placement.