Sensitivity Of Endoscopic Ultrasound-guided Fine-needle Aspiration Research Articles

The impact of biliary stents on the diagnostic yield of endoscopic ultrasound-guided fine needle aspiration for solid pancreatic lesions: A single-center retrospective study and meta-analysis.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is widely used for the pathological diagnosis of solid pancreatic lesions but in cases with obstructive jaundice, transpapillary sampling can be performed during endoscopic retrograde cholangiopancreatography with transpapillary biliary stent placement. Thus, it is still controversial whether EUS-FNA should be performed prior to endoscopic retrograde cholangiopancreatography with biliary stent placement or only after negative transpapillary sampling. The accuracy, sensitivity, and specificity of EUS-FNA for solid pancreatic lesions with or without indwelling biliary stents were retrospectively studied in patients undergoing EUS-FNA between January 2017 and December 2021. We also conducted a meta-analysis including our data to compare the accuracy and sensitivity of EUS-FNA with or without biliary stents. A total of 509 patients (40 with biliary stents and 469 without biliary stents) were included. The accuracy (77.5% vs. 94.5%, p < 0.001) and sensitivity (71.0% vs. 91.7%, p < 0.001) were lower in EUS-FNA with biliary stents. A meta-analysis confirmed that accuracy (odds ratio [OR] of 0.43, 95% confidence interval [CI] 0.29-0.62, p < 0.001) and sensitivity (OR of 0.46, 95% CI 0.33-0.64, p < 0.001) were lower in EUS-FNA with biliary stents. There were no statistically significant differences between plastic stents and self-expandable metallic stents for accuracy or sensitivity. The presence of biliary stents had a negative impact on the diagnostic performance of EUS-FNA, and EUS-FNA prior to endoscopic retrograde cholangiopancreatography with biliary stent placement should be considered in cases with obstructive jaundice.

Contrast-Enhanced Harmonic Endoscopic Ultrasound-Guided Puncture for the Patients with Pancreatic Masses

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is useful for the diagnosis of pancreatic masses. According to three meta-analyses, the sensitivity, specificity, and accuracy of EUS-FNA are 84-92%, 96-98%, and 86-91%, respectively. However, the occurrence of false-negative and false-positive results indicates that the diagnostic performance of EUS-FNA needs to be improved. Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is used for the characterization of pancreatic masses and can be applied to improve the performance of EUS-FNA. When CH-EUS is used to evaluate intratumor blood flow, an avascular area inside the pancreatic mass that is considered to be fibrosis is often detected. This area can be avoided by performing EUS-FNA under CH-EUS guidance. In this review, we summarize the data on contrast-enhanced harmonic endoscopic ultrasound-guided fine-needle aspiration (CH-EUS-FNA), which suggest that its benefit is still a matter of debate. Of eight studies analyzed, only one showed that CH-EUS improved the sensitivity of EUS-FNA. The future challenge is to determine under what circumstances CH-EUS-FNA is useful.

Evaluation of preoperative diagnostic methods for resectable pancreatic cancer: a diagnostic capability and impact on the prognosis of endoscopic ultrasound-guided fine needle aspiration

BackgroundA pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified.AimsTo evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer.MethodsBetween January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis.ResultsThe diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) (p < 0.001). The adverse event rate in ERCP was 10.2%, which was significantly higher than EUS-FNA (1.3%) (p = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not.ConclusionsEUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.

Clinical dilemma of endoscopic ultrasound-guided fine needle aspiration for resectable pancreatic body and tail cancer.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a first-line procedure for definitive tissue diagnosis of pancreatic cancer because of its high accuracy and low complication rate. The overall sensitivity of EUS-FNA for the diagnosis of pancreatic cancer is approximately 90%; however, its diagnostic ability for small lesions (<10 mm) remains limited. Although EUS-FNA is a relatively safe procedure, with an overall morbidity of ≤2%, it should be noted that needle tract seeding (NTS) can occur after EUS-FNA, which may affect the patient prognosis negatively. In patients with resected pancreatic tumors, preoperative EUS-FNA is not associated with an increased risk of postoperative recurrence. However, NTS after EUS-FNA for resectable pancreatic body and tail cancer has been highlighted recently, particularly by Japanese endoscopists. Thus, the use of preoperative EUS-FNA for the diagnosis of resectable pancreatic body and tail cancer has become a clinical dilemma that challenges gastroenterologists and must be carefully considered on a case-by-case basis by weighing the benefits and risks. This review summarizes the pros and cons of performing EUS-FNA in patients with resectable pancreatic body and tail cancer and provides valuable insight for gastroenterologists treating pancreatic cancer.

Factors influencing diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic and biliary tumors

Background and aim Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. Methods In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. Results A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8–71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0–74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. Conclusions The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

High Diagnostic Accuracy and Safety of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Malignant Lymph Nodes: A Systematic Review and Meta-Analysis

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is increasingly being used for diagnosing lymphadenopathy. We aim to systematically review the accuracy of EUS-FNA in differentiating benign and malignant mediastinal and abdominal lymph nodes (LNs). A comprehensive literature search was performed on multiple electronic databases through February 2020. A random or fixed effect model generated the pooled sensitivity, specificity, likelihood ratio (LR), and diagnostic odds ratio (DOR) of EUS-FNA. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. Twenty-six studies involving 2753 patients with 2833 LNs were included. In the differential diagnosis of benign and malignant LNs, EUS-FNA had a pooled sensitivity, specificity, positive LR, and negative LR of 87% (95% confidence interval [CI] 86-90%), 100% (95% CI 99-100%), 68.98 (95% CI 42.10-113.02), and 0.14 (95% CI 0.11-0.17), respectively. The pooled rate of adverse events associated with EUS-FNA was 1.57% (95% CI 1.06-2.24%). The summary receiver operating characteristic (SROC) yielded an area under the curve (AUC) of 0.9912. EUS-FNA performed in mediastinal LNs gained a sensitivity of 85% (95% CI 81-88%), while in abdominal LNs, it reached 87% (95% CI 82-91%). The sensitivity of the subgroup with rapid on-site evaluation (ROSE) was 91% (95% CI 89-93%), while non-ROSE was 85% (95% CI 82-87%). EUS-FNA is a sensitive, highly specific, and safe method for distinguishing benign and malignant mediastinal or abdominal LNs. However, the sensitivity of EUS-FNA still varies significantly among different centers.

2812 Impact of Rapid On-Site Evaluation (ROSE) on Endoscopic Ultrasound-Guided FNA of Pancreatic Cysts: A Five-Year Comparative Study Between Two Academic Institutions

INTRODUCTION: Endoscopic Ultrasound Guided-Fine Needle Aspiration (EUS-FNA) is considered the modality of choice for diagnosing intermediate pancreatic lesions. Rapid-on site evaluation (ROSE), when performed by a cytopathologist, has been suggested to improve the diagnostic yield of EUS-FNA. Prior studies were inconsistent regarding the benefit of ROSE. In our study, we evaluated the diagnostic yield of EUS-FNA in the presence of an on-site cytopathologist providing real-time feedback to the endoscopist compared to EUS-FNA alone in two academic hospitals. METHODS: We conducted a 2010-2015 retrospective chart review of all EUS-FNA performed at two academic medical centers (UT and UR). The policy at UT is to perform all EUS-FNA with ROSE, whereas it is not routinely done at UR. Cases where included when surgical pathology was available. Patients’ demographics, pancreatic cyst characteristics and EUS techniques were analyzed. EUS-FNA were considered valuable when it provided a classifying cytopathologic diagnosis. Student T-test and Analysis of Variance (ANOVA) were performed when appropriate for descriptive purposes. RESULTS: Forty-five cases (13 at UT, 32 at UR) were identified. EUS FNAs coupled with ROSE (UT) rendered 100% (13/13) valuable diagnoses, while those done with no cytopathologist on site (UR) had valuable diagnosis in 37.5% of the cases (12/32, P &lt; 0.0001). The sensitivity of EUS-FNA at UT was 85% compared to 33% at UR. There was no statistically significant difference in gender, age, site or size of the tumor. The mean number of needle passes at UT was 1.9 (range 1-6) vs. 1.1 (range 1-3) at UR. The majority of needles used were 19G (55%) at UT vs 22G (83%) at UR (P &lt; 0.001). Only one patient at UR had a minor cyst bleeding to the main pancreatic duct that required no therapeutic action. CONCLUSION: The results highlight the advantage of bed-side cytopathologist interaction with the endoscopist during EUS-FNA of pancreatic cysts. Absence of malignant cells despite suspicious ultrasound findings may have prompted more needle passes. The use of 19G needle may have improved outcomes with no significant increase of complications. In addition to the small sample size and the retrospective nature, the study is limited by the variability in personnel experience (endoscopists and cytopathologists) and the techniques used, indicating that further studies are necessary to confirm these findings.

Diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration for cystic and non-cystic pancreatic neuroendocrine tumors

Background and study aims Pancreatic neuroendocrine tumors (P-NENs) are rare tumors with malignant potential. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been shown to be superior to other imaging methods in preoperative localization and diagnosis of P-NENs. The objective of this study was to describe the EUS features of non-metastatic cystic and non-cystic P-NENs seen at a referral center and to evaluate the performance of EUS-FNA in diagnosis of P-NENs. Patients and methods All patients with histologically confirmed, non-metastatic P-NENs, which underwent EUS-FNA prior to surgical resection at the Moffitt Cancer Center between Jan 2005 and Dec 2012 were included. Clinical, endoscopic and pathologic information was abstracted from electronic medical records. Results Thirty-nine patients, all with non-functional P-NENs, were included in this study. Thirteen tumors were cystic and 26 were solid. Among the cystic tumors, 50 % were partly cystic and partly solid, and 50 % were fully cystic. The cystic tumors were more commonly seen at the body/tail, and the solid tumors were more uniformly distributed. Fluid could be aspirated from 50 % of the cystic tumors, all with a carcinoembryonic antigen level < 192 ng/mL. With surgical pathology as the gold standard, overall sensitivity of EUS-FNA in diagnosing cystic tumors was 62.5 %, and for solid tumors, 95 % ( P < 0.03). Conclusions EUS-FNA is much more sensitive in diagnosing solid P-NENs than cystic PNETs. Our results indicate that EUS-FNA may have higher sensitivity for diagnosis of cystic P-NENs than the reported sensitivity of EUS-FNA for all pancreatic cystic tumors.

Per-Pass Performance Characteristics of Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Malignant Solid Pancreatic Masses in a Large Multicenter Cohort.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely performed for the evaluation of pancreatic masses. We evaluated the performance characteristics of EUS-FNA in obtaining a diagnosis of pancreatic malignancy. We performed a multicenter study of patients who underwent EUS-FNA for a solid pancreatic mass. Endoscopic ultrasound-guided FNA was standardized using a 25-gauge needle, slow-pull stylet technique for specimen acquisition, and on-site cytopathology. For the primary analysis, only malignant cytology was regarded as positive. A secondary analysis was performed in which malignant and/or suspicious cytology was regarded as positive. A total of 138 patients underwent EUS-FNA. In the primary analysis, the sensitivity of EUS-FNA for malignancy was 56.7% on first pass, 73.3% on second pass, 83.3% on third pass, 89.2% on fourth pass, and 90.8% on fifth pass, with no increase beyond the fifth pass. In the secondary analysis, the sensitivity was 75.0% on first pass, 89.2% on second pass, 93.3% on third pass, and 95.8% on fourth pass, with no increase beyond the fourth pass. No significant relationship was seen between lesion size and diagnostic yield. Using a 25-gauge needle, the maximal diagnostic yield of EUS-FNA for a solid pancreatic mass is reached after 4 needle passes.

KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the cytologic diagnosis of pancreatic masses. The specificity of EUS-FNA approaches 100%, but the sensitivity is still low, and the high rate of indeterminate (atypical and suspicious) and false-negative results needs improvement. KRAS gene is frequently mutated in pancreatic ductal adenocarcinoma (PDAC) (up to 90%), and mutation analysis of KRAS has been proposed as diagnostic biomarker of PDAC. In most laboratories, KRAS mutation testing is performed by Sanger sequencing or real time-quantitative polymerase chain reaction (RT-qPCR), but these methods may give false-negative results in routine samples, mainly due to low cellularity. In order to increase the sensitivity of EUS-FNA, we propose a sequential approach for detecting KRAS mutations using mutant enriched-PCR (ME-PCR, sensitivity up to 0.1%) in cytologically indeterminate and negative samples tested wild-type by RT-qPCR. EUS-FNA specimens from 107 patients with pancreatic masses (51 males, 56 females, mean age 67 years) were cytologically examined. According to the Papanicolaou Society of Cytopathology guidelines, 50 cases (47%) were classified malignant, 15 (14%) suspicious, 13 (12%) atypical and 10 (9%) negative for malignancy; 18 cases (17%) were non-diagnostic. The overall specificity and sensitivity of cytological examination were 100% and 61%, respectively, when only negative and positive cases were considered; when atypical and suspicious were added to positive cases, the sensitivity increased to 95.1% and the specificity decreased to 85.7%. In all the cases, DNA was extracted from the cell-block and KRAS mutations were investigated by RT-qPCR, followed by ME-PCR in non-amplifiable and negative cases. The overall sensitivity and specificity of KRAS mutation testing alone were 79.3% and 100%; when KRAS mutation testing was performed in indeterminate and negative cytology, the sensitivity increased to 90% with specificity to 100%. Our data indicate that conventional cytology from EUS-FNA samples is highly specific for the diagnosis of pancreatic cancer. Indeterminate and negative cases need to be screened for KRAS mutations; this two-step approach may greatly improve the diagnostic accuracy of this method.

Esophageal Endosonography for the Diagnosis of Intrapulmonary Tumors: A Systematic Review and Meta-Analysis

Background: Biopsy-based diagnosis in patients with paraesophageal intrapulmonary tumors suspected of lung cancer is crucial for adequate treatment planning. Objective: To evaluate the performance of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis of intrapulmonary tumors located near or adjacent to the esophagus. Methods: We performed a systematic review (PROSPERO, CRD42016033737) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science on September 22, 2016, without date or language restrictions. We included studies that evaluated the yield and/or sensitivity of EUS-FNA for diagnosing intrapulmonary tumors. Yield was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis (malignant or nonmalignant) relative to the total number of patients on whom EUS-FNA was performed. Sensitivity was defined as the number of patients in whom EUS-FNA made a biopsy-proven diagnosis of malignancy relative to the total number of patients in whom the tumor was found to be malignant. We performed a random-effects meta-analysis. Results: Of 3,320 search results, 11 studies were included. Ten had a high risk of bias. The total number of patients was 313; the proportion of patients with malignancy ranged from 87 to 100% across these studies. The average yield was 0.90 (95% CI 0.82-0.95) and the average sensitivity was 0.92 (0.83-0.96). In the subgroup of prospective studies (n = 3), the average yield was 0.80 (0.56-0.93) and the average sensitivity was 0.83 (0.58-0.95). EUS-FNA-induced complications were reported for 5/256 patients (2.0%) for whom this information was available. Conclusions: Although the number of high-quality studies is limited, these findings suggest that EUS-FNA is safe and has a high yield for diagnosing intrapulmonary tumors.

Effect of the time of day and queue position in the endoscopic schedule on the performance characteristics of endoscopic ultrasound-guided fine-needle aspiration for diagnosing pancreatic malignancies.

Background and Objectives:Recent reports have indicated that the time of day may impact the detection rate of abnormal cytology on gynecologic cytology samples. The aim of this study was to determine if procedure time or queue position affected the performance characteristics of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing solid pancreatic malignancies.Patients and Methods:We conducted a retrospective study evaluating patients with solid pancreatic lesions in whom EUS-FNA was performed. Three timing variables were evaluated as surrogate markers for endoscopist fatigue: Procedure start times, morning versus afternoon procedures, and endoscopy queue position. Statistical analyses were performed to determine whether the timing variables predicted performance characteristics of EUS-FNA.Results:We identified 609 patients (mean age: 65.8 years, 52.1% males) with solid pancreatic lesions who underwent EUS-FNA. The sensitivity of EUS-FNA was 100% for procedures that started at 7 AM while cases that started at 4 PM had a sensitivity of 81%. Using start time on a continuous scale, each elapsed hour was associated with a 1.9% decrease in EUS-FNA sensitivity (P = 0.003). Similarly, a 10% reduction in EUS-FNA sensitivity was detected between morning and afternoon procedures (92% vs. 82% respectively, P = 0.0006). A linear regression comparing the procedure start time and diagnostic accuracy revealed a decrease of approximately 1.7% in procedure accuracy for every hour later a procedure was started. A 16% reduction in EUS-FNA accuracy was detected between morning and afternoon procedures (100% vs. 84% respectively, P = 0.0009). When the queue position was assessed, a 2.4% reduction in accuracy was noted for each increase in the queue position (P = 0.013).Conclusion:Sensitivity and diagnostic accuracy of EUS-FNA for solid pancreatic lesions decline with progressively later EUS starting times and increasing numbers of procedures before a given EUS, potentially from endoscopist fatigue and cytotechnologist fatigue.

Tu1635 A Randomized Multicenter Trial Comparing Capillary Suction and Standard Suction for Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) of Solid Pancreatic Lesions

Tu1635 A Randomized Multicenter Trial Comparing Capillary Suction and Standard Suction for Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) of Solid Pancreatic Lesions Payal Saxena*, Mohamad H. El Zein, Tyler Stevens, Ahmed Abdelgelil, Sepideh Besharati, Ahmed A. Messallam, Vivek Kumbhari, Alba Azola, Saowanee Ngamruengphong, Jennifer Brainard, Eun Ji Shin, Anne Marie Lennon, Vikesh K. Singh, Mouen Khashab Johns Hopkins, Baltimore, MD; Digestive Disease Institute, Cleveland Clinic, Cleveland, OH; Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH Background: Standard EUS-FNA procedures involve use of no-suction or suction (ST) aspiration techniques. A new aspiration method, the capillary suction technique (CT), involves pulling the needle stylet back slowly to create minimum negative pressure. A prior retrospective study showed higher sensitivity for diagnosis of pancreatic masses using the CT technique. There have been no randomized trials comparing the efficacy of the CT with standard ST Aim: 1) Primary aim was to compare the sensitivity of EUS-FNA using ST or CT for solid pancreatic lesions using a standard 22g needle. 2) Secondary endpoints were first pass diagnostic rate and acquisition of core tissue. Methods: All consecutive patients presenting for EUS-FNA of a solid pancreatic mass at two tertiary academic centers from 9/2013 to 11/2014 were randomized to CT or ST using a 22g needle (Expect, Boston Scientific). CT was performed with an assistant withdrawing 50% of the stylet length. ST was performed with a 10mL suction syringe. Both techniques were standardized to 15 to-and-fro movements for each pass until an adequate specimen was achieved as determined by rapid onsite cytology examination (ROSE). Fanning was performed at the discretion of the endoscopist. Patients were crossed-over to the alternate technique after 4 non-diagnostic passes. All visible core specimens were measured. Positive cytology or surgical histopathology was considered gold standard for malignancy. Negative cytology was confirmed with clinical data and/or imaging at 6 month followup. Results: Of 147 patients screened, 119 (mean age 65yr, 58% male) met inclusion criteria and were randomized to CT (nZ59) or ST (nZ60) (Figure 1). Baseline patient characteristics, including mean mass size, (2.9cm vs 3.2cm, pZ0.22) were similar in both groups. Malignant and benign diagnoses, use of fanning technique, technical success rates (96.6% vs 100%, pZ0.24) and cross-over rates (18.6% vs 18.3%, pZ0.97) were comparable. There were no adverse events. In an intention-totreat analysis, there was no difference in first pass diagnosis rate (40.7% vs 38.3%, pZns) or core specimen acquisition rates (59.3% vs 46.6%, pZns). Mean number of passes to diagnosis (1.9 vs 1.6, pZ 0.22) were equivalent. There was no significant difference in the sensitivity (90 % vs 89%, pZ 1.0), specificity (100% vs 100%, pZ 1.0), or diagnostic accuracy (88.1% vs 85%, pZ0.79) (table 1). Fanning was a not a predictor of diagnostic yield in either group (OR 2.29, pZ0.350 and OR 0.78, pZ0.75). Conclusion: Both capillary suction and standard suction techniques offer high and comparable diagnostic sensitivity of 90% with an average of less than 2 passes required for diagnosis of solid pancreatic lesions. The endosonographer may choose either technique; however, the suction technique may be preferable as coordination with an assistant is not required during FNA.

Improving the Diagnostic Accuracy of Endoscopic Ultrasound–Guided Fine-Needle Aspiration Using MicroRNAs

Brand RE, Adai AT, Centeno BA, et al. A microRNA-based test improves endoscopic ultrasound–guided cytologic diagnosis of pancreatic cancer. Clin Gastroenterol Hepatol 2014;12:1717–1723. Owing to its safety profile, diagnostic accuracy, and low risk of tumor seeding, endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) represents the preferred modality for achieving a tissue confirmation of pancreatic ductal adenocarcinoma (PDAC; J Cancer Res Clin Oncol 2012;138: 1433–1441; Gastrointest Endosc 2003;58:690–595; Endoscopy 2011;43:897–912). In a recent metaanalysis that included 41 studies and 4766 procedures, EUS-FNA had a pooled sensitivity of 87% and specificity 96% for the diagnosis of malignant pancreatic lesions (Pancreas 2013;42: 20–26). However, the sensitivity of EUS-FNA is lower in the setting of chronic pancreatitis (CP), where false-negative rates may be as high as 40% (Gastrointest Endosc 2005;62: 728–736l; Gastrointest Endosc 2009;70:70–79). Thus, there is substantial interest in improving the accuracy of cytopathology for diagnosing PDAC—and potentially informing long-term prognosis of this deadly cancer—using novel molecular markers such as microRNAs (miRNAs; Clin Cancer Res 2011;17:5812–5821). miRNAs are small, noncoding RNAs (17–25 nucleotides long) that regulate gene expression post-transcriptionally. These molecules are stable and easily recovered from tissue or blood, making EUS-FNA specimens suitable for analysis (Clin Chem 2008;54:1716–1724). Unique miRNA “signatures” have been evaluated using formalin-fixed, paraffin-embedded specimens, having >90% accuracy in distinguishing PDAC from CP and normal pancreata in limited studies (Clin Cancer Res 2011;17:5812–5821; Clin Chem 2008;54:1716–1724; Int J Cancer 2012;131:E86–95; Expert Rev Mol Diagn 2011;11:249–257). Using samples (n = 95) derived from formalin-fixed, paraffin-embedded tissues of PDAC and CP, Brand et al (Clin Gastroenterol Hepatol 2014;12:1717–1723) developed a miRNA panel and then analyzed its utility as a diagnostic test using pancreas tissue specimens (n = 229) derived from EUS-FNA. Starting with 11 candidate miRNAs applied to formalin-fixed, paraffin-embedded specimens (PDAC, n =52; CP, n = 43), the authors identified a panel of 5 miRNAs (−24, −130b, −135b, −148a, and −196a) having >95% agreement compared with standard histopathology when the miRNA classifier score was ≥0.5. Then, the authors applied this panel using polymerase chain reaction amplification techniques to EUS-FNA specimens prospectively collected at 8 participating centers. Only 1 FNA pass was dedicated for miRNA analysis, yet the rate of failed polymerase chain reaction amplification was only 1 in 229 (0.4%). Based on standard histopathology, the pretest probability of cancer was 202 in 228 (89%), with 184 of 202 cancers being PDAC (excluding non-PDAC cancers, the pre-test probability of PDAC was 184 of 202 [88%]). Although the prevalence of concomitant CP is not provided—the most common scenario in which the sensitivity of EUS-FNA is diminished—the sensitivity of cytopathology for detecting PDAC was 79% (145/184). By comparison, the miRNA panel correctly diagnosed PDAC in 152 of 184 patients (83%). The combination of cytopathology + miRNA resulted in a sensitivity/specificity of 167 of 184 (91%) and 25 of 26 (96%). Including 1 case of cholangiocarcinoma, the miRNA panel accurately detected adenocarcinoma in 130 of the 146 cases detected by cytopathology, with an 11% false-negative rate. In the setting of negative cytopathology and an miRNA panel score of <0.5, the posttest probability of PDAC (the false-negative rate of EUS-FNA cytopathology + miRNA) was 17 of 43 (40%). Because the sensitivity of achieving a diagnosis of PDAC increased from 79% using cytopathology alone to 91% when cytopathology was combined with an elevated miRNA panel, the authors concluded that a 5-miRNA classifier panel improves the performance characteristics of EUS-FNA.

Transesophageal pulmonary nodule biopsy using endoscopic ultrasonography

Parenchymal pulmonary nodules located in proximity to the mediastinum, vertebral column, major vessels, or behind the heart can be technically challenging and dangerous to biopsy using traditional image-guided techniques. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) can be used to access some of these difficult to reach lesions. The purpose of the present study was to report our experience with this technique in a consecutive cohort of selected patients. This was a retrospective cohort study. Eligible patients were identified from a prospective database. A transesophageal approach under real-time EUS guidance was performed using a 22-gauge needle. All patients underwent postprocedural chest radiography and were followed up at 30 days. During a 31-month period, 55 patients underwent EUS-guided lung biopsy. Confirmatory visual correlation of nodule localization within the lung parenchyma between computed tomography and EUS was possible in 100% of cases. The lung nodule distribution was 41.5% right upper lung, 18.9% right lower lung, 28.3% left upper lung, and 11.3% left lower lung. Histologic and cytologic sampling was adequate in 52 of the 55 procedures (94.5%). In all patients with adequate biopsy sampling, accurate pathocytologic diagnoses of the target parenchymal nodules were obtained. The accuracy and sensitivity of EUS-FNA were both 94.5% and consistent with the diagnosis on pathologic resection or clinical progression of disease, or both. No morbidity resulted from the procedure nor was observed at 30 days. EUS-FNA of parenchymal pulmonary nodules is safe and accurate and allows for biopsy of perimediastinal lung lesions not attainable using traditional techniques.

How Good Is Endoscopic Ultrasound–Guided Fine-Needle Aspiration in Diagnosing the Correct Etiology for a Solid Pancreatic Mass?

The objective of this study was to evaluate the accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in diagnosing the correct etiology for a solid pancreatic mass. Data extracted from EUS-FNA studies with a criterion standard (either confirmed by surgery or appropriate follow-up) were selected. Articles were searched in MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews. Pooling was conducted by both fixed- and random-effects models. Initial search identified 3610 reference articles, of these 360 relevant articles were selected and reviewed. Data were extracted from 41 studies (N = 4766) which met the inclusion criteria. Pooled sensitivity of EUS-FNA in diagnosing the correct etiology for solid pancreatic mass was 86.8% (95% confidence interval [CI], 85.5-87.9). Endoscopic ultrasound-guided FNA had a pooled specificity of 95.8% (95% CI, 94.6-96.7). Positive likelihood ratio of EUS was 15.2 (95% CI, 8.5-27.3), and the negative likelihood ratio was 0.17 (95% CI, 0.13-0.21). Endoscopic ultrasound-guided FNA is an excellent diagnostic tool to detect the correct etiology for solid pancreatic masses. When available, EUS-FNA should be strongly considered as the first diagnostic tool for sampling these lesions to optimize patient management.

Increased diagnostic yield of endoscopic ultrasound‐guided fine needle aspirates with flow cytometry and immunohistochemistry

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most sensitive and specific test for establishing a tissue diagnosis for many gastrointestinal malignancies; however, cytologic morphology alone may not be definitive for subsets of tumors. Our aim was to quantify the impact of the broad application of flow cytometry (FC) and immunohistochemistry (IHC) on EUS-FNA diagnostic yield. A retrospective chart review was performed on EUS procedures at a tertiary referral, academic medical center. All EUS-FNA cases performed over a 21-month period were examined. Of 606 EUS procedures reviewed during the period of study, 264 utilized FNA. After pancreatic cyst cases were excluded, 235 EUS-FNA cases for 221 patients were selected for analysis. For cases with subsequent histological evaluation, including the subset utilizing FC/IHC, the sensitivity of EUS-FNA was 89%, specificity was 100%, and accuracy was 91%. One quarter (58/235, 25%) of the tissue specimens underwent further testing by FC/IHC. There were 48 definitive diagnoses made in the subset utilizing FC/IHC. In 20 of the 48 diagnoses (42%), FC/IHC was deemed critical to the diagnosis, and without FC/IHC testing in those cases, the overall sensitivity and accuracy of EUS-FNA would be reduced to 74 and 77%, respectively. FC/IHC allowed for six diagnoses rarely or not previously described by EUS-FNA. Application of FC/IHC improves characterization predominantly for nonadenocarcinoma tumor subtypes and may lead to a diagnostic result for tumors not previously characterized by EUS-FNA. With an adequate tissue sample, broad application of FC/IHC increases the diagnostic yield of EUS-FNA.

Unusual, metastatic, or neuroendocrine tumor of the pancreas: A diagnosis with endoscopic ultrasound-guided fine-needle aspiration and immunohistochemistry

Background/Aim:To determine the yield of endoscopic ultrasound–guided fine-needle aspiration (EUS–FNA) in combination with immunostains in diagnosing unusual solid pancreatic masses (USPM) in comparison with pancreatic adenocarcinoma (ACP).Patients and Methods:All EUS–FNA of solid pancreatic masses performed with a 22-gauge needle were included. Data on clinical presentations, mass characteristics, presence of pancreatitis, yield of tissue, and final diagnosis were compared between the two groups. On site cytopathology was provided and additional passes were requested to perform immunostains.Results:Two hundred and twenty-nine cases with either adenocarcinoma or USPM were included. The median age of the cohort was 65 years. ACP (210/229, 92%) accounted for the majority of the cases. The USPM included neuroendocrine (NET) masses (n=13), metastatic renal carcinoma (n=3), metastatic melanoma (n=1), lymphoma (n=1), and malignant fibrous histiocytoma (n=1). Subjects with ACP were significantly more likely to present with loss of weight (P=0.02) or obstructive jaundice (P<0.001). Subjects with ACP were more likely to have suspicious/atypical FNA biopsy results as compared with USPM (10% vs 0%). The sensitivity of EUS–FNA with immunostains was 93% in ACP as compared with 100% in USPM. Diagnostic accuracy was higher in USPM as compared with ACP (100% vs 93%).Conclusions:EUS–FNA using a 22-gauge needle with immunostains has excellent diagnostic yield in patients with USPMs, which is comparable if not superior to the yield in pancreatic adenocarcinoma.

Molecular Biologic Approach to the Diagnosis of Pancreatic Carcinoma Using Specimens Obtained by EUS-Guided Fine Needle Aspiration

We review the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), a rapid, safe, cost-effective, and accurate diagnostic modality for evaluating pancreatic tumors. EUS-FNA is currently used for the diagnosis and staging of pancreatic tumors. The sensitivity of EUS-FNA for pancreatic malignancy ranges from 75% to 94%, and its specificity approaches 100% in most studies. However, EUS-FNA has some limitations in the diagnosis of well-differentiated or early-stage cancers. Recent evidence suggests that molecular biological analysis using specimens obtained by EUS-FNA improves diagnostic sensitivity and specificity, especially in borderline cytological cases. It was also reported that additional information regarding patient response to chemotherapy, surgical resectability, time to metastasis, and overall survival was acquired from the genetic analysis of specimens obtained by EUS-FNA. Other studies have revealed that the analysis of KRAS, MUC, p53, p16, S100P, SMAD4, and microRNAs is helpful in making the diagnosis of pancreatic carcinoma. In this paper, we describe the present state of genetic diagnostic techniques for use with EUS-FNA samples in pancreatic diseases. We also discuss the role of molecular biological analyses for the diagnosis of pancreatic carcinoma.

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy. Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy. Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70). Immunohistochemical staining for p53 and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.