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Objectives: Endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) for primary prophylaxis (PP) of gastric varices (GV) is controversial. This study evaluates the safety and efficacy of this intervention., Methods: Patients treated for PP of GV bleeding by EUS injection of CYA with or without coils were identified. Endoscopic techniques, outcomes, and adverse events (AEs) were reviewed and compared with a group treated for secondary prophylaxis (SP). Patients were followed until: (i) loss to follow-up; (ii) GV bleeding; (iii) interventional radiology or surgery decompression; (iv) liver transplant; or (v) death or comfort care., Results: One hundred and nineteen patients (61 men; mean 59 ± 12 years) underwent EUS for PP (n = 24) or SP (n = 95). The PP group was treated with CYA alone (n = 18) or with coils (n = 4). Eight (33%) mild (n = 6) or moderate (n = 2) AEs and no index GV bleeding occurred during a mean of 6.1 ± 5.9 months follow-up. Repeat EUS in 22 (92%) PP patients showed 7 (32%) residual GVs, which were retreated with CYA alone (n = 6) or with coils (n = 1). Two (29%) mild (n = 1) or moderate (n = 1) AEs occurred after repeat EUS and 1/22 (5%) index GV bleed occurred during a mean 23 ± 25 months follow-up. Compared to the SP group, the PP group had lower Model for End-stage Liver Disease (MELD) score (P = 0.03), fewer GV stigmata (P < 0.001), required less CYA (P = 0.019) during index EUS, and had a longer time between index and surveillance EUS (P = 0.014). The incidence of AEs and GV bleeding between the two groups were similar., Conclusion: Posttreatment GV bleeding and AEs are similar following EUS-guided primary and secondary GV prophylaxis., (© 2023 Japan Gastroenterological Endoscopy Society.)

The evolution of endoscopic ultrasound (EUS) from a diagnostic to a therapeutic procedure has resulted in a paradigm shift toward endoscopic management of disease states that previously required percutaneous or surgical approaches. The past few years have seen additional techniques and devices that have enabled endoscopists to expand its diagnostic and therapeutic capabilities. Some of these techniques initially were reported more than a decade ago; however, with further device development and refinement in techniques there is potential for expanding the application of these techniques and new technologies to a broader group of interventional gastroenterologists. Lack of formalized training, devices, and prospective data regarding their use in addition to a scarcity of guidelines on implementation of these technologies into clinical practice are contributing factors impeding the growth of the field of interventional EUS. In April 2019, the American Gastroenterological Association's Center for Gastrointestinal Innovation and Technology conducted its annual Tech Summit and a key session focused on interventional EUS. This article is a White Paper generated from the conference, discusses the published literature pertaining to the topic of interventional EUS, and outlines a proposed framework for the implementation of interventional EUS techniques into clinical practice. Three primary areas of interventional EUS are addressed: (1) EUS-guided access; (2) EUS-guided tumor ablation; and (3) endohepatology. There was general agreement among participants on several key components. The introduction of these novel interventions requires better tools, more data on safety/outcomes, and improved training for endoscopists. Participants also agreed that widespread implementation and use of these techniques will require support from Gastrointestinal Societies and other key stakeholders including payers. Continued work by the Gastrointestinal Societies and manufacturers to provide training programs, appropriate equipment/work environments, and policies that motivate endoscopists to adopt new techniques is essential for growing the field of interventional EUS., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic injection of cyanoacrylate into gastric varices may be performed by EUS-guided fine needle injection (EUS-FNI) or direct endoscopic injection (DEI). The aim of this study is to compare the rate of recurrent GV bleeding and adverse events between DEI and EUS-FNI for treatment of GV., Methods: In a single-center study, a retrospective cohort of patients with actively/recently bleeding or high-risk GV treated with DEI were compared with a prospective cohort of similar patients treated with EUS-FNI. Repeat endoscopy after index treatment was performed 3 months later or earlier if rebleeding occurred. The main outcomes assessed were rates of GV or overall rebleeding and adverse events., Results: Forty patients (mean age 57.2 ± 9.1 years, 73% male) and 64 patients (mean age 58.0 ± 12.5 years, 52% male) underwent DEI and EUS-FNI, respectively. Compared to the DEI group, the frequency of isolated gastric varices type 1 (IGV1) were higher (p < 0.001) but MELD scores were lower (p = 0.004) in the EUS-FNI group. At index endoscopy, EUS-FNI utilized a lower mean volume of cyanoacrylate (2.0 ± 0.8 mL vs. 3.3 ± 1.3 mL; p < 0.001) and injected a greater number of varices (1.6 ± 0.7 vs. 1.1 ± 0.4; p < 0.001) compared to DEI. Overall, GV rebleeding [5/57 (8.8%) vs. 9/38 (23.7%); p = 0.045] and non-GV-related gastrointestinal bleeding [7/64 (10.9%) vs. 11/40 (27.5%); p = 0.030] were less frequent in the EUS-FNI group compared to the DEI group, respectively. Adverse event rates were similar (20.3% vs. 17.5%, p = 0.723)., Conclusions: EUS-guided CYA injection of active or recently bleeding GV in patients with portal hypertension appears to decrease the rate of GV rebleeding despite injection of more varices and less CYA volume during the initial endoscopic procedure. Adverse events are similar between the two groups. EUS-FNI appears to be the preferred strategy for treatment of these patients.

Purpose of Review: Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined., Recent Findings: Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm.

Background and Aims: EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis., Methods: Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used., Results: A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively., Conclusions: EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: Incidental pancreatic cysts are often detected during abdominal imaging and require follow-up since some have malignant potential. Endoscopic ultrasound (EUS) is highly sensitive for pancreatic diseases, yet the prevalence of incidental pancreatic cysts discovered with EUS is unknown. The objective of the study was to determine its prevalence by EUS., Methods: A prospective cross-sectional study was conducted. Patients undergoing EUS for nonpancreatic indications and without known pancreatic abnormality were recruited to assess the prevalence of pancreatic cysts and its characteristics. Risk factors were determined by logistic regression., Results: We enrolled 341 patients (mean age, 59 years; 187 females) and found 46 incidental pancreatic cysts (median [range], 5 [2-80] mm) in 32 patients (9.4%). Branch duct intraductal papillary mucinous neoplasm was the most common finding. Seven cysts were larger than 1 cm and 1 adenocarcinoma was discovered. Multivariate logistic regression showed an association between pancreatic cysts and older age (odds ratio, 1.04 per year; 95% confidence interval, 1.01-1.08) and female sex (odds ratio, 3.08; 95% confidence interval, 1.25-7.45)., Conclusions: In our population, the prevalence of incidental pancreatic cyst discovered on EUS was 9.4% and the majority were less than 1 cm. Increasing age and female sex were associated with the development of pancreatic cysts.

Background: The accuracy of EUS in the locoregional assessment of ampullary lesions is unclear., Objectives: To compare EUS with ERCP and surgical pathology for the evaluation of intraductal extension and local staging of ampullary lesions., Design: Retrospective cohort study., Setting: Tertiary-care referral center., Patients: All patients who underwent EUS primarily for the evaluation of an ampullary lesion between 1998 and 2012., Intervention: EUS., Main Outcome Measurements: Comparison of EUS sensitivity/specificity for intraductal and local extension with ERCP and surgical pathology by using the area under the receiver-operating characteristic (AUROC) curves and outcomes of the subgroup referred for endoscopic papillectomy., Results: We identified 119 patients who underwent EUS for an ampullary lesion, of whom 99 (83%) had an adenoma or adenocarcinoma. Compared with ERCP (n = 90), the sensitivity/specificity of EUS for any intraductal extension was 56%/97% (AUROC = 0.77; 95% confidence interval [CI], 0.64-0.89). However, when using surgical pathology as the reference (n = 102), the sensitivity/specificity of EUS (80%/93%; AUROC = 0.87; 95% CI, 0.76-0.97) and ERCP (83%/93%; AUROC = 0.88; 95% CI, 0.77-0.99) were comparable. The overall accuracy of EUS for local staging was 90%. Of 58 patients referred for endoscopic papillectomy, complete resection was achieved in 53 (91%); in those having intraductal extension by EUS or ERCP, complete resection was achieved in 4 of 5 (80%) and 4 of 7 (57%), respectively., Limitation: Retrospective design., Conclusions: EUS and ERCP perform similarly in evaluating intraductal extension of ampullary adenomas. Additionally, EUS is accurate in T-staging ampullary adenocarcinomas. Future prospective studies should evaluate whether EUS can identify characteristics of ampullary lesions that appropriately direct patients to endoscopic or surgical resection., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Since the introduction of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA), EUS has assumed a growing role in the diagnosis and management of pancreatic ductal adenocarcinoma (PDAC). The objective of this review is to discuss the various applications of EUS and EUS-FNA in PDAC. Initially, its use for detection, diagnosis and staging will be described. EUS and EUS-FNA are highly accurate modalities for detection and diagnosis of PDAC, this high accuracy, however, is decreased in specific situations particularly in the presence of chronic pancreatitis. Novel techniques such as contrast-enhanced EUS, elastography and analysis of DNA markers such as k-ras mutation analysis in FNA samples are in progress and might improve the accuracy of EUS in the detection of PDAC in this setting and will be addressed. EUS and EUS-FNA have recently evolved from a diagnostic to a therapeutic technique in the management of PDAC. Significant developments in therapeutic EUS have occurred including advances in celiac plexus interventions with direct injection of ganglia and improved pain control, EUS-guided fiducial and brachytherapy seed placement, fine-needle injection of intra-tumoral agents and advances in EUS-guided biliary drainage. The future role of EUS and EUS in management of PDAC is still emerging.

Objectives: This study aimed to correlate endoscopic ultrasound (EUS) criteria and pathology in patients with chronic pancreatitis (CP)., Methods: Endoscopic ultrasound reports and pathology specimens were reviewed from patients with known or suspected CP who underwent surgery within 1 year of EUS. The following information was abstracted: EUS criteria for CP, corresponding pathology results, and histologic features. The EUS and pathology results were correlated., Results: One hundred patients (55 men; mean age, 54 years) underwent a pancreatic resection, median of 50 days (range, 1-363 days). The mean (SD) fibrosis scores in the head and body/tail specimens were 7.9 (3.0) and 6.4 (3.8), respectively (P = 0.02). The main pancreatic duct (MPD) dilation and irregularity were associated with moderate and severe fibrosis. Lobularity with honeycombing was associated with intralobular and interlobular fibrosis. Severe CP was associated with the following: lobularity with honeycombing, hyperechoic foci with shadowing, hyperechoic foci without shadowing, MPD dilation, MPD irregularity, and dilated side branches., Conclusions: Endoscopic ultrasound of the pancreas head may be considered in the evaluation of CP. The EUS criteria that were associated with severe CP included the following: lobularity with honeycombing, hyperechoic foci with shadowing, dilated MPD, irregular MPD, and dilated side branches. The importance of pancreatic ductal changes should not be minimized in the evaluation of CP.

Background: The presence of debris within a pseudocyst may impair success of endoscopic drainage., Objective: To compare the clinical outcomes and adverse-event rates of EUS-guided pseudocyst drainage with and without a nasocystic drain for the management of pancreatic pseudocysts with viscous solid debris-laden fluid., Design: Retrospective study., Setting: Single, tertiary-care referral center., Patients: Consecutive patients with pancreatic pseudocysts managed by EUS-guided drainage: those with solid debris who underwent drainage via nasocystic drains alongside stents (n = 63) and those with solid debris who underwent drainage via transmural stents only (n = 24)., Intervention: Drainage via nasocystic drains alongside stents or drainage via transmural stents only., Main Outcome Measurements: The primary outcomes were short-term success and long-term success of the procedures. The secondary outcomes were procedure-related adverse events and reintervention., Results: The patients with viscous solid debris-laden fluid whose pseudocysts were drained by both stents and nasocystic tubes had a 3 times greater short-term success rate compared with those who had drainage by stents alone (P = .03). On 12-month follow-up, complete resolution of pseudocysts with debris drained via stents alone was less (58%) compared with those with debris who underwent drainage via nasocystic drains alongside stents (79%; P = .059). The rate of stent occlusion was higher in cysts with debris drained by stents alone (33%) compared with those drained via nasocystic drains alongside stents (13%; P = .03)., Limitations: Retrospective design; limited sample size., Conclusion: In patients with pseudocysts with viscous debris-laden fluid, EUS-guided drainage by using a combination of a nasocystic drain and transmural stents improves clinical outcomes and lowers the stent occlusion rate compared with those who underwent drainage via stents alone., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Accurate preoperative diagnosis and staging of cholangiocarcinoma (CCA) remain difficult., Objective: To evaluate the utility of EUS in the diagnosis and preoperative evaluation of CCA., Design: Observational study of prospectively collected data., Setting: Single tertiary referral hospital in Indianapolis, Indiana., Patients: Consecutive patients with CCA from January 2003 through October 2009., Interventions: EUS and EUS-guided FNA (EUS-FNA)., Main Outcome Measurements: Sensitivity of EUS for the detection of a tumor and prediction of unresectability compared with CT and magnetic resonance imaging (MRI); sensitivity of EUS-FNA to provide tissue diagnosis, by using surgical pathology as a reference standard., Results: A total of 228 patients with biliary strictures undergoing EUS were identified. Of these, 81 (mean age 70 years, 45 men) had CCA. Fifty-one patients (63%) had distal and 30 (37%) had proximal CCA. For those with available imaging, tumor detection was superior with EUS compared with triphasic CT (76 of 81 [94%] vs 23 of 75 [30%], respectively; P < .001). MRI identified the tumor in 11 of 26 patients (42%; P = .07 vs EUS). EUS identified CCA in all 51 (100%) distal and 25 (83%) of 30 proximal tumors (P < .01). EUS-FNA (median, 5 passes; range, 1-12 passes) was performed in 74 patients (91%). The overall sensitivity of EUS-FNA for the diagnosis of CCA was 73% (95% confidence interval, 62%-82%) and was significantly higher in distal compared with proximal CCA (81% vs 59%, respectively; P = .04). Fifteen tumors were definitely unresectable. EUS correctly identified unresectability in 8 of 15 and correctly identified the 38 of 39 patients with resectable tumors (53% sensitivity and 97% specificity for unresectability). CT and/or MRI failed to detect unresectability in 6 of these 8 patients., Limitation: Single-center study., Conclusion: EUS and EUS-FNA are sensitive for the diagnosis of CCA and very specific in predicting unresectability. The sensitivity of EUS-FNA is significantly higher in distal than in proximal CCA., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Pancreatic neuroendocrine tumors (PNTs) are rare tumors with malignant potential. EUS and EUS-guided FNA (EUS-FNA) have been shown to be superior to other imaging methods in the preoperative localization and diagnosis of PNTs., Objectives: To evaluate the clinical presentation, EUS morphology, and sensitivity of EUS-FNA cytology in a large consecutive cohort with histologically and/or cytologically confirmed PNTs., Design: Retrospective study of all consecutive patients from July 1995 to November 2006 who underwent EUS for a known or suspected PNT and had a subsequently histologically confirmed PNT., Setting: Tertiary referral center., Patients: Ninety-two patients with suspected PNT., Interventions: EUS evaluation with or without EUS-FNA of PNTs., Main Outcome Measurements: Clinical and EUS features of PNTs and sensitivity of EUS-FNA for the diagnosis of PNTs., Results: Ninety-two patients underwent EUS; 76 patients had confirmed histopathology, of whom 69 (91%) were symptomatic. Patients with functional PNTs presented with diarrhea, peptic ulcer disease, and hypoglycemia. Tumor locations and echogenic features were similar except that nonfunctional PNTs tended to be larger and have cystic features. Patients with malignant PNTs were older (P = .03), presented with abdominal pain, and had larger tumors (P = .0006) with irregular margins. Eighty-nine percent of patients underwent EUS-FNA. Sensitivity of EUS-FNA for the diagnosis of a PNT was 87%. Sensitivity of EUS-FNA was similar in functional and nonfunctional PNTs. The sensitivity of EUS-FNA was higher for malignant PNTs (P = .008)., Limitations: Retrospective single tertiary center., Conclusions: EUS and EUS-FNA are sensitive tools, especially in cases of suspected symptomatic PNTs in which other imaging modalities have failed., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: EUS has less than optimal interobserver agreement for the diagnosis of chronic pancreatitis. The newly developed Rosemont consensus scoring system includes weighted criteria and stricter definitions for individual features., Objective: The primary aim was to compare the interobserver agreement of standard and Rosemont scoring., Setting: Multiple tertiary-care institutions., Intervention: Fifty EUS videos were interpreted by 14 experts. Each expert interpreted the videos on two occasions: First, the videos were read by using standard scoring (9 criteria). Second, after viewing a presentation of the Rosemont classification, the same experts re-read the videos by using Rosemont scoring., Main Outcome Measurements: Fleiss' kappa (K) statistics are reported with 95% confidence intervals (CI)., Results: The interobserver agreement was "substantial" (K = 0.65 [95% CI, 0.52-0.77]) for Rosemont scoring and "moderate" (K = 0.54 [95% CI, 0.44-0.66]) for standard scoring; however, the difference was not statistically significant (P = 0.12)., Limitations: The sample size does not allow detection of differences in K of <0.25., Conclusion: Use of the Rosemont classification did not significantly increase interobserver agreement for EUS diagnosis of chronic pancreatitis compared with standard scoring., (2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Bispectral index monitoring (BIS) is a quantitative assessment of brain cortical activity. The aim of this study was to determine if BIS-guided nurse-administered propofol sedation would decrease by > or = 20% both recovery time and propofol dose compared to standard propofol sedation for endoscopic ultrasound (EUS). Prospectively, eligible outpatients were randomized to BIS-guided or standard propofol sedation during EUS. Propofol was given by nurses in intermittent boluses with sedation targeted at a BIS score of < 65-75. For the control group, the nurse was blinded to BIS scores and sedation was titrated to a modified observer's assessment of alertness/sedation scale (MOAA/S) score < or = 3. Of 50 patients enrolled, data for 44 randomized to BIS-guidance (n = 24) and the control group (n = 20) were evaluated. Between the BIS-guided and control group there was no difference between the mean procedure duration, total propofol dose, recovery time, mean intraoperative MOAA/S, and mean BIS score. Compared to standard propofol sedation for EUS, BIS-guided propofol sedation offers no significant decrease in postprocedure recovery times or propofol doses.

Context: Endoscopic ultrasound (EUS) with EUS-guided fine needle aspiration (EUS-FNA) has been increasingly utilized to differentiate malignant/pre-malignant pancreatic cysts from those that are benign or have low malignant potential., Objective: To determine the utility of EUS morphology, EUS-FNA cytology and cyst fluid analysis to distinguish mucinous cystic neoplasms from non-mucinous cystic neoplasms based on histopathology following surgical resection., Design: A retrospective, single center case series., Participants: Patients who underwent EUS and EUS-FNA of known or suspected pancreatic cysts followed by surgical resection. The final diagnosis was based on histopathology., Setting: Patients were divided in two groups: mucinous cystic neoplasms and non-mucinous cystic neoplasms. Patients with intraductal papillary mucinous tumors were excluded., Main Outcome Measures: Clinical profiles and EUS findings., Results: Forty-eight patients (mean age: 52 years; 29 females, 19 males) were identified: 16 mucinous cystic neoplasms and 32 non-mucinous cystic neoplasms. There were more women in the mucinous cystic neoplasm group compared to the non-mucinous cystic neoplasm group (88% vs. 47%; P=0.011) but the two groups were otherwise similar. The sensitivity, specificity and frequency of cases correctly identified of EUS-FNA cytology for the diagnosis of mucinous cystic neoplasms were 12.5% (95% CI: 2.2-37.2%), 90.6% (95% CI: 75.0-97.5%) and 64.6% (95% CI: 50.4-77.0%), respectively. Median cyst fluid CEA for the mucinous cystic neoplasm group (277 ng/mL; n=14) was significantly higher (P=0.002) than the non-mucinous cystic neoplasm group (1.5 ng/mL; n=21). Cyst fluid CEA greater than 800 ng/mL had a sensitivity of 42.9% (95% CI: 21.3-67.4%) and specificity of 95.2% (95% CI: 75.6-99.9%) for the diagnosis of mucinous cystic neoplasm. On the other hand, a cyst fluid CEA greater than a best cut-off ranging from 3.5 to 8.5 ng/mL had a sensitivity of 92.9% (95% CI: 66.5-100%), a specificity of 66.7% (14/21; 95% CI: 45.2-83.0%), and an accuracy of 81.1% with a frequency of cases correctly identified of 77.1% (95% CI: 60.7-88.2%)., Conclusions: EUS-FNA cytology and cyst fluid CEA greater than 800 ng/mL are insensitive but highly specific for differentiating mucinous cystic neoplasms from non-mucinous cystic neoplasms. EUS morphology alone cannot distinguish between the two groups.

Despite technical advances in staging non-small cell lung cancer (NSCLC), accurate staging remains a challenge. Endoscopic ultrasound is useful in staging NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role in the absence of lymphadenopathy on CT has not been well defined. Therefore, we sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and followed prospectively. EUS-guided fine-needle aspiration was performed on sites that were suspicious for metastases. Surgical pathology after thoracotomy was used as the reference standard for assessing accuracy. Sixty-two (86%) patients underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients (12%) and influenced management in 18 (25%) of all patients in this study. EUS detected malignant mediastinal lymphadenopathy more frequently in patients with lower lobe and hilar cancers combined compared with upper lobe cancers (p = 0.004). EUS played a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC compared with upper lobe NSCLC.