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Despite the indisputable significance of human symbolic cognition and behavior, we still lack a detailed understanding of the mechanisms by which such capacities evolved during the Paleolithic. An important source of evidence is constituted by archaeological findings of intentional markings left on rock and bone surfaces, but these are often opaque with respect to their original meaning and function. Here we present experimental work that systematically addresses the relation between properties of intentional markings and their cognitive implications to support inferences about their past functions. Participants reproduced engraved markings dating to c. 100.000 years ago from the South African Blombos and Diepkloof sites in three conditions of cultural transmission: as part of an aesthetic, identity marking, and communicative activity. Their reproductions were then used as stimuli in a suite of five perceptual experiments to investigate differences in their cognitive implications over time and explore similarities with the archaeological record. [ABSTRACT FROM AUTHOR]

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. 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. 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). EUS-FNB outperforms bite-on-bite biopsy both in terms of diagnostic yield and safety profile. [ABSTRACT FROM AUTHOR]

It is unclear whether patients with intraductal papillary mucinous neoplasia harbor a higher risk of developing extrapancreatic malignancies. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

standard B-mode EUS assessment and EUS-guided tissue acquisition present sub-optimal diagnostic yield in the differential diagnosis of gastric submucosal tumors (SMTs). to evaluate the performances of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) to differentiate gastric SMTs and predict malignancy risk of gastrointestinal stromal tumors (GIST). a retrospective analysis was performed retrieving consecutive patients with gastric SMTs who underwent EUS between 2009 and 2014. Patients with available EUS video recordings and histological diagnosis were included. De-identified videos were presented to experts who made a diagnosis on B-mode EUS and CH-EUS. fifty-four patients (29 female, 64-year-old) were included. Final diagnoses were 40 GISTs (8 high-grade), 9 leiomyomas, 5 rare SMTs. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the differential diagnosis of GIST were 95.0% vs. 85.0%, 57.1% for both techniques, and 85.2% vs. 77.8%, respectively. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the estimation of the malignancy GISTs risk were 62.5% vs. 100%, 83.3% vs. 82.1%, and 78.9% vs. 86.1%, respectively. CH-EUS showed better diagnostic performance than B-mode EUS in differentiating leiomyomas and risk stratification of GIST. When considering high-grade GISTs, the addition of CH-EUS allowed an improvement in diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Percutaneous endoscopic gastrostomy (PEG) is the technique of choice for providing enteral nutrition in patients with functioning gastrointestinal tract. Available guidelines cover indications and procedural management for PEG placement, while there is no consensus about subsequent replacement with gastrostomy feeding tubes (GFT) and their management. We hypothesized that GFT replacement, according to a standardized protocol supervised by a trained gastroenterologist could be integrated into the home health care system. To evaluate the safety and cost-efficacy of home GFT replacement. All consecutive patients who underwent elective home GFT replacements from July 2016 to December 2019 were prospectively enrolled; all procedural details and outcomes have been recorded. Overall, 235 GFT replacements in 84 patients [40.5% male, 79.5 (74–94) years] were included. Among these, 230 (97.8%) were completed at patients' home while in five cases (2.2%) patients were referred to the hospital to confirm appropriate GFT placement. No adverse event occurred. An overall cost reduction of 46.8% was obtained, leading to €124 savings per procedure and up to €29,000 savings for the entire study period. When performed electively according to a standardized protocol, home GFT replacement is safe and effective, and leads to relevant cost reduction. [ABSTRACT FROM AUTHOR]

Material artefacts evolve by cumulative cultural evolution (CCE), the accumulation of adaptive modifications over time. We present a large-scale experiment investigating the CCE of a social artefact in transmission chains, each containing 8 adult human participants (N = 408). The social artefact is what Wittgenstein calls a ‘language game’, the subset of language used to perform a particular activity; in the present study the language game is to communicate a route on a map. Two social learning conditions were compared: Observational Learning and Social Coordinative Learning. Participants tried to accurately communicate a route on a map to the next person in their transmission chain. Over the experimental generations the routes were reproduced with progressively higher accuracy in both conditions, demonstrating the CCE of the language game. The rate of CCE was comparable across conditions, but route reproduction accuracy was consistently higher in the Social Coordination condition compared to the Observation condition. In both conditions performance improved due to the accumulation of adaptive patterns of verbal route descriptions, and the progressive elimination of non-adaptive patterns. Whereas change in the content of the language game was similar across conditions, change to the communication process differed between the Observation and Social Coordination conditions. In conclusion, like material artefacts, social artefacts, in our case the language game, evolve by cumulative cultural evolution. [ABSTRACT FROM AUTHOR]

Background Percutaneous endoscopic gastrostomy is the preferred option for providing enteral nutrition, allowing for an improvement in survival and quality of life. Aim To evaluate risk factors for early and delayed mortality after gastrostomy placement. Methods A single-center retrospective analysis of a prospectively-collected database including all patients undergoing gastrostomy placement for enteral nutrition was performed. Two operators performed all the procedures according to the most recent guidelines. Results Analysis included data on 438 patients [178 male; 80.5 (72–86) year-old]. Indications for PEG were stroke (34.0%), dementia (31.3%), neurodegenerative disorders (18.5%), coma (9.1%) and cancer (7.1%). No periprocedural adverse events was observed. Mean survival was 14.6 ± 3.4 months; 1-month and 3-month mortality rates were 4.0% and 8.1%, respectively. Severe hypernatremia (≥150 mmol/L) was independently related to 1-month mortality (odds ratio 25.4; P < 0.0001), while C-reactive protein level > 4.3 mg/dL was independently related to 3-month mortality (odds ratio 5.3; P = 0.003). Kaplan–Meier and Cox-regression analysis identified male gender (hazard ratio 2.32; P = 0.0002), severe hypernatremia (hazard ratio 4.3; P < 0.0001), C-reactive protein > 4.3 mg/dL (hazard ratio 3.5; P = 0.0014), leukocytosis (hazard ratio 1.97; P = 0.0036) and presence of underlying malignancy (hazard ratio 2.4; P = 0.0013) as independent risk factors for long-term mortality. Discussion Presence of severe hypernatremia and increased C-reactive protein levels were strongly correlated with early and delayed mortality in our population. Studies are necessary to understand whether correcting underlying dehydration and inflammation further improves patients’ outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Endoscopic ultrasound (EUS) is accurate for the diagnosis of choledocholithiasis; however, data are lacking regarding the prediction of stone number and size. Aims To evaluate the concordance between EUS and endoscopic retrograde cholangiopancreatography (ERCP) in stone number and size assessment. Methods We performed a retrospective analysis of consecutive patients undergoing ERCP due to detection of choledocholithiasis by EUS. Concordance between EUS and ERCP was defined as difference in stone diameter <30% and perfect match in stone number. Results Among 116 patients, 25% had sludge, 37.9% had single and 37.1% had multiple stones. Overall concordance was 62.9%. Sludge was correctly assessed in 85.7%, single stone in 81.3% and multiple stones in 45.1% ( P = 0.0001). EUS was accurate in 78.8% of patients who underwent both procedures in the same session, but only in 61.9% in those who underwent ERCP within 1 week. Multivariate analysis identified the single-session approach (odds ratio 2.894; P = 0.035) and multiple stones (odds ratio 0.244; P = 0.001) as independent predictors of concordance. Conclusions Concordance between EUS and ERCP was correlated to the single session approach and inversely correlated to the presence of multiple stones. EUS may predict potentially difficult ERCP allowing to plan the best treatment strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. Franseen and Fork-tip needles, particularly 22-gauge size, showed the highest performance for tissue sampling of pancreatic masses, with low confidence in estimates. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

BACKGROUND: Given the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD). STUDY DESIGN: An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle. SETTING & PARTICIPANTS: Prevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers. INTERVENTIONS: Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32). OUTCOMES & MEASUREMENTS: All-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method. RESULTS: There was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06 versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54 mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 +/- 0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03). LIMITATIONS: This is a small preliminary intervention study with a high dropout rate and problematic generalizability. CONCLUSION: On-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index. A larger study is required to confirm these results. Copyright © 2008 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Background: Gastric juice is usually discarded during upper-GI endoscopy. Objective: By using a novel device, the Mt 21-42, we evaluated the potential of this important organic fluid in clinical practice, exploring its contribution to the diagnosis of Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa (AGOM). Design and Patients: A multicenter study (17,907 patients; 10 endoscopy units) estimated the frequency of diagnosis of AGOM and H pylori infection in routine endoscopic practice. A prospective study (216 patients) at 1 of these units aimed to determine the real prevalence of these conditions and the possible benefits of gastric juice analysis. We considered gastric juice pH and ammonium concentration, endoscopic and histologic features, serologic parameters for atrophy and H pylori, gastric acid secretion, and costs. Results: We found that H pylori infection and, even more markedly, AGOM were greatly underdiagnosed in routine endoscopic practice (20.1% and 0.8% vs 49.1% and 12.5% in the prospective study, respectively), because of the intrinsic limitations of the conventional tests and lack/inappropriateness of biopsy planning. Gastric-juice analysis proved to be a cheap, simple, and effective way to prevent such underdiagnosis and allowed detection of atrophic gastritis and H pylori in 96% and 98% of cases, and saved costs (cost-effectiveness ratio 209 vs 274-5047). Conclusions: Gastric juice provided a valuable source of clinicopathologic information that, properly analyzed, allowed detection of the main risk factors for gastric cancer (H pylori and atrophic gastritis), overcoming the diagnostic limitations associated with these conditions and also producing time and cost savings. [Copyright &y& Elsevier]

Abstract: Endoscopic ultrasonography and endoscopic ultrasonography-guided fine needle aspiration are well-established techniques, encompassing a variety of diagnostic and therapeutic applications. Along with traditional indications that constitute everyday clinical practice in all endoscopic ultrasonography centres, new indications are emerging that resemble the continuing research carried on in this field. Some of these are innovative applications, developed by highly experienced endosonographers and with a putative role for clinical practice in the near future. Others are merely experimental applications, carried out on in animal models or in highly selected groups of patients, opening up new fascinating areas of research but not for imminent introduction in clinical practice. The purpose of this review, after summarising the present indications of endoscopic ultrasonography, is to focus on the future applications and try to establish their possible advent, either in the near or in the far future. [Copyright &y& Elsevier]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

EUS-guided FNA (EUS-FNA) is the criterion standard for the diagnosis of solid pancreatic lesions. Several studies assessed the role of repeat EUS-FNA (rEUS-FNA) after an inconclusive examination. Our aim was to evaluate the pooled diagnostic accuracy of rEUS-FNA after a nondiagnostic result. We conducted systematic research on electronic databases (Medline, PubMed, EMBASE) and a meta-analysis to obtain pooled sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. A summary receiver operating characteristic curve was used to calculate area under the curve. Subgroup analysis was used to assess the role of rapid on-site evaluation (ROSE). Twelve studies (505 patients) were included. Sensitivity was 77% (66%-86%), specificity 98% (78%-100%), and positive and negative predictive values 99% (98%-100%) and 61 (60%-63%), respectively. At 73% of disease prevalence (pretest probability), positive rEUS-FNA increased the disease probability to 99%, whereas a negative result decreased the disease probability to 39%. The sensitivity was 83% (64%-93%) and specificity 98% (80%-100%) when ROSE was available and 65% (57%-73%) and 94% (31%-100%) when not available. The number needed to diagnose was 1.2 (1.1-2.3) and 1.7 (1.4-8.3) in ROSE-positive and ROSE-negative cases, respectively. The number of correctly diagnosed cases increased from 6 (1-7) to 8 (4-9) of 10 patients without and with ROSE, respectively. This study objectively substantiated the added value of rEUS-FNA for the diagnosis of solid pancreatic masses in cases of a previous nondiagnostic or inconclusive result. Moreover, our data suggested that ROSE may be beneficial in this setting, because it increased the proportion of definitive diagnoses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]