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Best Practices in Endoscopic Ultrasound–Guided Fine-Needle Aspiration
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:697–703
PERSPECTIVES IN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Best Practices in Endoscopic Ultrasound–Guided Fine-Needle Aspiration SHYAM VARADARAJULU,* PAUL FOCKENS,‡ and ROBERT H. HAWES§ *Division of Gastroenterology-Hepatology, University of Alabama at Birmingham, Birmingham, Alabama; ‡Division of Gastroenterology-Hepatology, Academic Medical Center, Amsterdam, The Netherlands; §Florida Hospitals Institute for Minimally Invasive Therapy, University of Central Florida, Orlando, Florida
Over the past 2 decades, endoscopic ultrasound– guided fine-needle aspiration has evolved to become an indispensable tool for tissue acquisition in patients with gastrointestinal tumors. The technique is useful for biopsy of mucosal and submucosal lesions in which prior endoscopic biopsies have been nondiagnostic; to sample peri-intestinal structures such as lymph nodes; and to sample masses in the pancreas, liver, adrenal glands, gallbladder, and bile duct. Also, with the advent of neoadjuvant therapies for diseases such as pancreatic cancer, most patients require a tissue diagnosis before initiating treatment. This review provides a perspective on technical issues that are key for best practices in endoscopic ultrasound-guided fine-needle aspiration. Keywords: Cytopathology; Tissue Collection Procedure; Suction; Histology.
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here are several factors that may determine the outcomes of endoscopic ultrasound (EUS)– guided fine-needle aspiration (FNA): the degree of technical difficulty, the gauge of an FNA needle, use of suction to aspirate tissue, use of a stylet in the needle assembly, special maneuvers to procure better quality tissue, presence or absence of an onsite cytopathologist, need for histology when cytology is indeterminate or insufficient, and, finally, the experience and skills of an endosonographer performing the procedure. In this review we summarize evidence-based answers to the basic questions that an endosonographer is facing on a daily basis.
Does the Degree of Difficulty Vary Between Endoscopic Ultrasound–FineNeedle Aspiration Procedures? The degree of technical difficulty varies depending on the location of the lesion being targeted (Figure 1). In general, transesophageal and transgastric FNAs are technically easier and transduodenal FNAs are more challenging. When a lesion such as a mediastinal lymph node or pancreatic body mass is being sampled, the tip of the echoendoscope is relatively straight and there is no difficulty in puncturing the mass. On the other hand, when a pancreatic uncinate or a bile duct mass is targeted via the transduodenal route, the tip of the echoendoscope is acutely angulated, resulting in 2 challenges, as follows: (1) the needle assembly cannot be secured freely to the biopsy channel, and/or (2) the FNA needle cannot be advanced
freely into the target lesion. The first challenge can be overcome easily by withdrawing the echoendoscope and thereby straighten its shaft, and with the “up/down” dial deflected completely down, the needle is secured to the biopsy channel. The echoendoscope then is advanced into the duodenum for performing an FNA. The most common reason for not being able to advance a needle into the target lesion is because the tip of the needle is bent in line with the curvature of the torqued echoendoscope and this generates resistance to free passage of the needle (Figure 2A). This technical limitation can be overcome by advancing the echoendoscope to the second portion of the duodenum and then shortening it (endoscopic retrograde cholangiopancreatography maneuver) so that the tip of the echoendoscope is straight. This would enable a free range of movement for the needle (Figure 2B). The disadvantage with a short scope position is that the echoendoscope is relatively unstable and tends to recoil into the stomach during the motion of an FNA. Although a thin-caliber (25G) or a more flexible larger needle can be used to achieve better range of movement, the needle must never be advanced forcefully because it inadvertently can puncture the scope or get itself bent out of shape.
Bottom Line Transduodenal sampling of pancreatic or bile duct masses is technically more difficult than other FNA procedures. It is imperative that the tip of the echoendoscope is kept as straight as possible to facilitate easy puncture of the mass.
Is the Gauge of a Needle Important? Cytology EUS-guided FNA can be performed with 25G, 22G, or 19G needles. When choosing a particular needle, there are several considerations: (1) which needle will provide the optimal yield of cells, (2) how much flexibility is required to access a lesion, and (3) which will minimize complications? Four randomized trials have attempted to identify the optimal needle for performing FNAs (Table 1). Of the 3 studies that compared Abbreviations used in this paper: EUS, endoscopic ultrasound; FNA, fine-need aspiration; TNB, Trucut needle biopsy. © 2012 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2012.03.017
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Figure 1. Illustration of the degree of technical difficulty with EUSguided FNA.
the 22G and 25G needles,1–3 although there was no significant difference in diagnostic accuracy, there was a trend toward better performance with the 25G needle for FNA of pancreatic head masses. In one study that compared the 19G and 22G needles, better diagnostic accuracy and superior cellular material were acquired using the 19G needle.4 However, there was a significantly higher technical failure rate with the 19G needle for FNA of pancreatic head masses. Although not a randomized trial, another study prospectively compared the 19G Trucut needle and the 22G and 25G FNA needles for sampling of pancreatic mass lesions in 24 patients.5 The overall diagnostic accuracy of the 25G, 22G, and 19G Trucut needle was 91.7%, 79.7%, and 54.1%, respectively. When the diagnostic accuracy of the 25G, 22G, and 19G Trucut needles were assessed in relationship to the location of the mass in the pancreas, for head/ uncinate lesions, these were 83.3%, 58.3%, and 8.3%, respectively. There was no significant difference between the 3 needle types for evaluation of pancreatic body and tail masses. In all the earlier-described studies, the safety profile of the FNA needles was excellent without any significant difference in complication rates.
Histology There are 2 limitations to EUS-guided FNA: (1) the diagnostic accuracy is impacted by the presence of an onsite cytopathologist to render diagnosis, and (2) certain neoplasms such as stromal cell tumors and lymphomas may be difficult to diagnose without histologic samples because their tissue architecture and morphology are essential for accurate pathologic assessment.6 Also, histologic tissue can provide a definitive diagnosis for benign diseases that may not always be possible with cytologic samples. To overcome these limitations and to improve diagnostic accuracy, a 19G Trucut needle biopsy (EUSTNB; Cook Endoscopy, Winston-Salem, NC) was developed to procure larger amounts of tissue with conserved architecture that would enable histologic analysis.6 The overall diagnostic accuracy of the EUS-TNB for evaluating suspicious lesions at various sites in the body is reported to be 75% to 84%7,8 and 61% to 67.5% for pancreatic masses.8,9 Although the EUS-TNB technique has some advantages over FNA, the rigidity induced by its 19G caliber and the mechanical friction of the firing mechanism produced by the torqued echoendoscope limits its use for evaluating pancreatic head and duodenal lesions.8,9 To overcome this limitation, a new 19G EUS-FNA device recently was
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developed (ProCore; Cook Endoscopy) with reverse bevel technology to enable the acquisition of core specimens for histologic analysis. In a large prospective study from Europe, histologic samples were obtained successfully with this new 19G FNB device in a majority of patients with diagnostic accuracy of more than 90%.10 However, some technical difficulties were encountered when performing transduodenal passes. The same FNB device also is available in a 22G platform to facilitate easy transduodenal sampling. The role of the standard 19G FNA needle for yielding histologic samples was assessed prospectively in a recent study.11 Of the 120 patients who underwent EUS-guided tissue acquisition, the procedure was technically successful in 119 patients (98.9%) and an adequate histologic sample was obtained in 116 patients (97.5%). A major limitation of the study was that patients with pancreatic head or uncinate masses were excluded. Because the standard 19G needle is too stiff to navigate the transduodenal route, a flexible 19G needle (Flex 19; Boston Scientific, Natick, MA) made of nitinol recently was introduced. Clinical studies evaluating its efficacy are currently underway.
Bottom Line Although the performance of the 22G and 25G needles is equivalent for FNA of all lesions including pancreatic body/ tail masses, because of its thin caliber, the 25G needle appears to be marginally better for sampling pancreatic head/uncinate lesions. A standard 19G or the 19G ProCore needle can procure histologic specimens in more than 90% of cases with the caveat that transduodenal sampling can be technically difficult.
Does Suction Have a Role in Endoscopic Ultrasound–Guided FineNeedle Aspiration? The role of suction at EUS-guided FNA remains debated. It is thought that suction, although increasing the quantity, diminishes the quality of an aspirate. Two randomized trials12,13 have attempted to address this issue and included FNA of lymph nodes and pancreatic masses (Table 2). In both trials, the use of suction did not improve the diagnostic yield of FNA. In one trial, the use of suction yielded better cellularity but did not improve the likelihood of obtaining a correct diagnosis.12
Figure 2. (A) The echoendoscope is in the long-scope position with an acutely angulated tip. This precludes free passage of the needle to deploy fiducials within a bile duct mass. (B) The echoendoscope is in the short-scope position with a straightened tip. The needle passage is much easier, facilitating fiducial placements within the bile duct mass.
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Table 1. Randomized Trials Comparing the Different Gauge Needles for EUS-Guided FNA of Solid Mass Lesions Study
Number
Camellini et al1
127
Fabbri et al2 Siddiqui et al3 Song et al4
50 131 117
Type of lesion
Needles
Diagnostic accuracy
Remarks
All lesions
22G vs 25G
77.8% vs 78.1%; P ⫽ NS
Pancreatic masses
22G vs 25G
86% vs 94%; P ⫽ NS
All lesions Pancreatic/peripancreatic masses
22G vs 25G 22G vs 19G
87.5% vs 95.5%, P ⫽ NS 78.9% vs 94.5%; P ⫽ .01
25G was better for uncinate masses and 22G was better for subepithelial masses Trend toward better yield with 25G — Technical success for FNA of pancreatic head masses was significantly less with the 19G needle. The 19G needle yielded significantly better cellular material
NS, not significant.
Bottom Line
Bottom Line
The use of suction at EUS-guided FNA yields specimens that are more bloody and without any improvement in diagnostic yield. For this reason, FNA of solid lesions or lymph nodes must be initiated without suction. If the aspirate obtained is scant, such as in chronic pancreatitis, then suction can be used to procure a better aspirate.
Are There Advantages to Use of a Stylet in Endoscopic Ultrasound–Guided Fine-Needle Aspiration? The presence of a stylet in an FNA assembly is to prevent the tip of the needle from being blocked by a plug of digestive wall tissue before entering the target lesion. However, the use of the stylet during individual FNA passes can be labor-intensive and may increase the risk of accidental needlestick injury. Three randomized trials14 –16 have evaluated the role of a stylet during EUS-guided FNA (Table 3). In all 3 trials, the use of a stylet did not improve the diagnostic yield for malignancy. In one study, the sample adequacy was better when a stylet was not used,14 and in all 3 trials the use of a stylet increased the bloodiness of the specimen. Table 2. Randomized Trials Evaluating the Role of Suction in EUS-Guided FNA Study Wallace et al12a Diagnostic yield Blood in specimen Cellularity Puri et al13b Diagnostic yield Blood in specimen Cellularity aFNA bFNA
Patients, n
Suction
No suction
P
43 Not improved More blood
Same No
.73 .0004
Better
Same
.01
52
of lymph node. of pancreatic mass.
92.3% 76.9% 100%
80% 88.5% 100%
.10 .14 1.0
There is no advantage to using a stylet during EUSFNA. The sample tends to be more bloody and without any difference in diagnostic yield. Because the FNA needle already is preloaded with a stylet, it is all right that the first pass be performed with a stylet but it should be removed for subsequent passes. However, the stylet should not be discarded because it is very useful for controlled expression of aspirates on to the slides.
Do Specific Maneuvers Improve the Diagnostic Yield of Endoscopic Ultrasound–Guided Fine-Needle Aspiration The center of a cancerous mass is usually more necrotic than the periphery and hence is more likely to yield nondiagnostic tissue when sampled.17 Therefore, to overcome this limitation, it has been suggested that aspiration of lesions at the periphery or in multiple areas may improve the diagnostic accuracy.18 Some endosonographers use a “fanning” technique Table 3. Randomized Trials Evaluating the Role of a Stylet in EUS-Guided FNA Study
No.
Sahai et al14 Sensitivity for malignancy Bloody specimen Sample adequacy Rastogi et al15 Minimal blood Diagnosis of malignancy ⬎50% cellularity Wani et al16 Minimal blood Diagnosis of malignancy ⬎50% cellularity
111
NS, not significant.
Stylet
No stylet
P
87%
83%
NS
75% 75%
52% 87%
⬍.0001 .01
50% 23%
41% 28%
.04 .29
15%
16%
NS
18.9% 38.7%
7.4% 36.1%
.02 .48
50%
45.9%
NS
101
162
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Figure 3. Illustration of the fanning technique of FNA in which the needle samples 4 different areas within a tumor mass.
of FNA, in which the needle is positioned at 4 different areas within a mass and then moved back and forth multiple times in each area to procure tissue (Supplementary Video 1). Sampling usually is initiated at the left margin of the tumor mass and then fanned until the right margin of the tumor is sampled (Figure 3) or multiple passes can be made in different areas of the mass to procure tissue. The trajectory of the needle can be altered using either the “up/down” endoscope dial or the elevator.
Bottom Line It appears that targeting the periphery of a mass as well as using the fanning principle is superior to the standard approach for EUS-guided FNA of pancreatic masses.
Does the Presence of an Onsite Cytopathologist Help? All studies published (Table 4) have shown that the presence of a cytopathologist during EUS-guided FNA improves diagnostic yield, decreases unsatisfactory samples, reduces the need for more passes, and, consequently, reduces the procedural duration.19 –21 In a recent study, 182 patients with pancreatic masses underwent EUS-guided FNA with (n ⫽ 95) or without (n ⫽ 87) an onsite cytopathologist.22 The presence of an onsite cytopathologist was associated with a significantly lower number of inadequate samples (1% vs 12.6%) and a higher diagnostic sensitivity (96.2% vs 78.2%). Also, a significantly higher number of needle passes was performed when an onsite cytopathologist was not available. In another study that compared the performance of a cytotechnician and an endoscopy
nurse for assessment of specimen adequacy, the rates of definitive diagnosis were significantly better and an inconclusive diagnosis occurred significantly less often when specimens were evaluated by a cytotechnician.23 In the United States, more than 50 advanced endoscopy fellows graduate annually with expertise in EUS. As the job market saturates in major metropolis and in academic medical centers, several of these novice endosonographers relocate to smaller cities where access to onsite cytopathology is limited. Despite being adequately trained, because of this limitation, their diagnostic yield at EUS-guided FNA suffers. Several steps can be undertaken to overcome this limitation. First, when an onsite cytopathologist is not available, most studies recommend that at least 3 passes be performed on lymph nodes and 6 to 7 passes on pancreatic masses to maximize the diagnostic yield.12,24,25 A dedicated pass must be performed for cell block should there be a need for additional studies such as flow cytometry or immunohistochemical staining. Second, procuring a histologic sample using a 19G or the reversely beveled needle can establish a diagnosis in more than 90% of patients.10,11 Third, every attempt must be made to obtain a high-quality specimen by adapting a fanning technique. Fourth, if possible, a trained cytotechnician must be used or the endosonographer should consider training himself or herself in the basics of cytopathology to ascertain specimen adequacy. Details on processing an FNA specimen is beyond the scope of this review. However, knowing the basic details is important to improve the outcomes of the procedure. In general, 2 types of smears can be prepared from the FNA specimen: air dried or alcohol fixed. Air dried smears are stained rapidly with DiffQuik (Dade Diagnostics, Miami, FL) and used for rapid onsite cytologic evaluation. Alcohol fixation preserves nuclear features and is stained by Papanicolaou or H&E stains. However, for lesions that may require special staining, cell block preparation is recommended. For cell block, the FNA specimen is placed into liquid media and sent to the laboratory where it is spun into a pellet, formalin-fixed, paraffin-embedded, and sectioned for standard H&E staining. Liquid-based cytology (Thin prep; Cytyc, Inc, Marlborough, MA, and SurePath; TriPath, Inc, Burlington, NC) is an automated process designed to minimize the technical problems associated with manual preparation. This method provides high cell preservation and uniform monolayer dispersion of cells into a confined area of the slide.26 However, disadvantages of this method include increased cost and inability to provide immediate cytologic assessment to the endosonographer unless the specimen is split into 2 parts, one for Diff-Quik and the other for liquid prep. This preparation also may lead to loss of background mucin, which is problematic because this is an important diagnostic clue for mucin-producing pancreatic tumors. In cases in which initial cytology is indeterminate, combining routine cytology with fluorescence in
Table 4. Select Studies Evaluating the Role of Onsite Cytopathology Service at EUS-Guided FNA Study
Patients, n
Diagnostic yield, OP vs no OP
Indeterminate samples, OP vs no OP
Unsatisfactory, OP vs no OP
Klapman et al19 Iglesias–Garcia et al22 Alsohaibani et al23
195 182 104
78% vs 32%, P ⫽ .001 97% vs 86%, P ⫽ .01 77% vs 53%, P ⫽ .01
10% vs 12%, P ⫽ .9 2.1% vs 10.3%, P ⫽ .02 23% vs 47%, P ⫽ .001
9% vs 20%, P ⫽ .003 1% vs 13%, P ⫽ .002 0% vs 17%, P ⫽ NS
OP, onsite pathology; NS, not significant.
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Table 5. Studies Evaluating the Value of Repeat EUS-Guided FNA Study
Proportion of repeat EUS-guided FNA cases
Indication
Diagnostic accuracy or impact
Eloubeidi et al29 DeWitt et al30 Nicaud et al31
24 of 517 (4.6%) pancreatic masses 73 of 8396 (0.8%) EUS examinations 30 of 3895 (0.77%) EUS examinations
Pancreatic masses 55% pancreatic masses Pancreatic masses
84% 63% 61%
situ hybridization and K-ras/p53 analysis may improve the diagnostic yield.27
Bottom Line The presence of an onsite cytopathologist or cytotechnician is a major determinant of diagnostic sensitivity in EUSFNA. If onsite cytopathology is not available, performing an adequate number of FNA passes using the fanning technique and procuring an additional specimen for histopathology/cell block can improve the diagnostic yield.
What if the Fine-Needle Aspiration Is Indeterminate? An FNA can be indeterminate even in the hands of an expert endosonographer. This is encountered more commonly when the following occurs: (1) performing an EUS-guided FNA of pancreatic mass lesions in the background of chronic pancreatitis, (2) if the lesion is in the uncinate process of the pancreas it may be difficult to visualize the lesion and/or obtain tissue, and (3) when cytology interpretation is indeterminate or difficult to interpret.28 In our experience, the diagnostic yield of EUS-guided FNA plateaus after 7 to 8 passes and then reaches a point of diminishing yield. Persisting with the procedure beyond this point yields a specimen that is mostly bloody and nondiagnostic. At present, there is no universally accepted protocol on how to manage patients with a high clinical suspicion for pancreatic cancer, but have negative cytology by EUS-guided FNA. The 3 most viable options are as follows: (1) clinical observation with repeat EUS-guided FNA in 2 to 4 months, (2) surgical exploration, or (3) CT-guided biopsy. CT-guided biopsy is less favorable owing to risk of seeding the needle track and causing a worse outcome even in patients who are not surgical candidates. If the suspicion of malignancy is very high and the patient is a good surgical candidate, and the lesion appears to be resectable, then the best option is often surgical resection. As the degree of suspicion for malignancy decreases, the health status of the patient is marginal, and the resectability is borderline, then repeat EUS-guided FNA is probably the best course of action. Also, if the patient or surgeon is reluctant to move forward with an open or laparoscopic exploration, then repeat EUS-guided FNA is a reasonable option. Three studies29 –31 have shown that a repeat EUS-guided FNA under such circumstances yields a correct diagnosis in 61% to 84% of patients (Table 5). Two of 3 studies comprised only of pancreatic masses and more than 50% of patients in another study also included pancreatic lesions. Also, combining fluorescence in situ hybridization and K-ras/p53 analysis may improve the diagnostic yield in such patients.27,32
Bottom Line The most common indication for repeat EUS-guided FNA is for evaluation of pancreatic masses. Performing a repeat
EUS guided-FNA (after a failed index procedure) in patients with high clinical suspicion of cancer appears to be a reasonable approach given the excellent safety profile of the procedure and a diagnostic accuracy of more than 60% under such circumstances.
Does Surgeon Experience Influence the Outcomes of a Procedure? Because FNAs of pancreatic masses are more technically challenging than other lesions, 2 studies have examined the learning curve of EUS-guided FNA in this patient cohort.33,34 In the first study of 57 patients with pancreatic mass lesions who underwent EUS-guided FNA by a self-taught endosonographer, the diagnostic sensitivities for malignancy from the first to last 10 quintiles were 30%, 40%, 70%, 90%, and 80%, respectively.33 In another study of 300 consecutive patients with pancreatic mass lesions who underwent EUS-guided FNA by an endosonographer with advanced endoscopy training, when the patients were divided into 3 groups (100 each), the median number of passes required to establish a diagnosis decreased significantly with surgeon experience.34 However, there was no significant difference in diagnostic accuracy between the 3 groups (group 1, 92%; group 2, 92%; group 3, 95%).
Bottom Line There certainly is a learning curve, at least, for EUSFNA of pancreatic masses. Although the diagnostic accuracy may plateau after a threshold number of procedures, the procedural expertise continues to improve with experience.
Are There Other Specific Recommendations to Optimize Endoscopic Ultrasound–Fine-Needle Aspiration Outcomes? Cyst Lesions Although uncommon, infection may develop secondary to aspiration of cystic lesions in the pancreas, mediastinum, and elsewhere.35 Performing multiple needle passes into a cyst appears to increase the risk of infection, as does failure to aspirate all the cyst fluid completely. It is recommended that prophylactic antibiotics be administered and continued for up to 48 hours for EUS-guided FNA of cyst lesions.36 In patients with complex cyst lesions in whom the clinical suspicion for malignancy is high, the solid component of the cyst must be aspirated for cytologic analysis. For the sake of efficiency, a 19G needle is most suited for performing cyst aspirations. However, if the cyst is small (⬍2 cm), a 22G needle may be used for aspiration. When aspirating a cyst, a change in echogenicity, from anechoic to hyperechoic, is indicative of intracystic hemorrhage.37 If this is observed, the procedure should be terminated and the patient monitored for hemodynamic stability for
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2 hours after the procedure. Clinically significant hemorrhage has not been reported in the literature and these incidences of intracystic bleeding almost always seem to be self-contained.
Conclusions In this review, we have attempted to provide a perspective on best practices in EUS-guided FNA. It is important to be cognizant that EUS-guided FNA is a multistep procedure. There is no one answer or single strategy to the different challenges that one encounters in clinical practice. However, by being attentive to the different steps involved and by adapting the best practices outlined in this review, one can expect to have optimal technical and clinical outcomes in a majority of their procedures.
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36. Adler DG, Jacobson BC, Davila RE, et al. ASGE guideline: complications of EUS. Gastrointest Endosc 2005;61:8 –12. 37. Varadarajulu S, Eloubeidi MA. Frequency and significance of acute intracystic hemorrhage during EUS-FNA of cystic lesions of the pancreas. Gastrointest Endosc 2004;60:631– 635.
Reprint requests Address requests for reprints to: Shyam Varadarajulu, MD, Division of Gastroenterology-Hepatology, University of Alabama School of Medicine, JT 664, 625-19th Street S, Birmingham, Alabama 35249. e-mail: [email protected]; fax: (205) 975-6381. Conflicts of interest The authors disclose the following: all authors are consultants for Boston Scientific Corporation, Olympus Corporation.
PERSPECTIVES IN CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Best Practices in Endoscopic Ultrasound–Guided Fine-Needle Aspiration SHYAM VARADARAJULU,* PAUL FOCKENS,‡ and ROBERT H. HAWES§ *Division of Gastroenterology-Hepatology, University of Alabama at Birmingham, Birmingham, Alabama; ‡Division of Gastroenterology-Hepatology, Academic Medical Center, Amsterdam, The Netherlands; §Florida Hospitals Institute for Minimally Invasive Therapy, University of Central Florida, Orlando, Florida
Over the past 2 decades, endoscopic ultrasound– guided fine-needle aspiration has evolved to become an indispensable tool for tissue acquisition in patients with gastrointestinal tumors. The technique is useful for biopsy of mucosal and submucosal lesions in which prior endoscopic biopsies have been nondiagnostic; to sample peri-intestinal structures such as lymph nodes; and to sample masses in the pancreas, liver, adrenal glands, gallbladder, and bile duct. Also, with the advent of neoadjuvant therapies for diseases such as pancreatic cancer, most patients require a tissue diagnosis before initiating treatment. This review provides a perspective on technical issues that are key for best practices in endoscopic ultrasound-guided fine-needle aspiration. Keywords: Cytopathology; Tissue Collection Procedure; Suction; Histology.
T
here are several factors that may determine the outcomes of endoscopic ultrasound (EUS)– guided fine-needle aspiration (FNA): the degree of technical difficulty, the gauge of an FNA needle, use of suction to aspirate tissue, use of a stylet in the needle assembly, special maneuvers to procure better quality tissue, presence or absence of an onsite cytopathologist, need for histology when cytology is indeterminate or insufficient, and, finally, the experience and skills of an endosonographer performing the procedure. In this review we summarize evidence-based answers to the basic questions that an endosonographer is facing on a daily basis.
Does the Degree of Difficulty Vary Between Endoscopic Ultrasound–FineNeedle Aspiration Procedures? The degree of technical difficulty varies depending on the location of the lesion being targeted (Figure 1). In general, transesophageal and transgastric FNAs are technically easier and transduodenal FNAs are more challenging. When a lesion such as a mediastinal lymph node or pancreatic body mass is being sampled, the tip of the echoendoscope is relatively straight and there is no difficulty in puncturing the mass. On the other hand, when a pancreatic uncinate or a bile duct mass is targeted via the transduodenal route, the tip of the echoendoscope is acutely angulated, resulting in 2 challenges, as follows: (1) the needle assembly cannot be secured freely to the biopsy channel, and/or (2) the FNA needle cannot be advanced
freely into the target lesion. The first challenge can be overcome easily by withdrawing the echoendoscope and thereby straighten its shaft, and with the “up/down” dial deflected completely down, the needle is secured to the biopsy channel. The echoendoscope then is advanced into the duodenum for performing an FNA. The most common reason for not being able to advance a needle into the target lesion is because the tip of the needle is bent in line with the curvature of the torqued echoendoscope and this generates resistance to free passage of the needle (Figure 2A). This technical limitation can be overcome by advancing the echoendoscope to the second portion of the duodenum and then shortening it (endoscopic retrograde cholangiopancreatography maneuver) so that the tip of the echoendoscope is straight. This would enable a free range of movement for the needle (Figure 2B). The disadvantage with a short scope position is that the echoendoscope is relatively unstable and tends to recoil into the stomach during the motion of an FNA. Although a thin-caliber (25G) or a more flexible larger needle can be used to achieve better range of movement, the needle must never be advanced forcefully because it inadvertently can puncture the scope or get itself bent out of shape.
Bottom Line Transduodenal sampling of pancreatic or bile duct masses is technically more difficult than other FNA procedures. It is imperative that the tip of the echoendoscope is kept as straight as possible to facilitate easy puncture of the mass.
Is the Gauge of a Needle Important? Cytology EUS-guided FNA can be performed with 25G, 22G, or 19G needles. When choosing a particular needle, there are several considerations: (1) which needle will provide the optimal yield of cells, (2) how much flexibility is required to access a lesion, and (3) which will minimize complications? Four randomized trials have attempted to identify the optimal needle for performing FNAs (Table 1). Of the 3 studies that compared Abbreviations used in this paper: EUS, endoscopic ultrasound; FNA, fine-need aspiration; TNB, Trucut needle biopsy. © 2012 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2012.03.017
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Figure 1. Illustration of the degree of technical difficulty with EUSguided FNA.
the 22G and 25G needles,1–3 although there was no significant difference in diagnostic accuracy, there was a trend toward better performance with the 25G needle for FNA of pancreatic head masses. In one study that compared the 19G and 22G needles, better diagnostic accuracy and superior cellular material were acquired using the 19G needle.4 However, there was a significantly higher technical failure rate with the 19G needle for FNA of pancreatic head masses. Although not a randomized trial, another study prospectively compared the 19G Trucut needle and the 22G and 25G FNA needles for sampling of pancreatic mass lesions in 24 patients.5 The overall diagnostic accuracy of the 25G, 22G, and 19G Trucut needle was 91.7%, 79.7%, and 54.1%, respectively. When the diagnostic accuracy of the 25G, 22G, and 19G Trucut needles were assessed in relationship to the location of the mass in the pancreas, for head/ uncinate lesions, these were 83.3%, 58.3%, and 8.3%, respectively. There was no significant difference between the 3 needle types for evaluation of pancreatic body and tail masses. In all the earlier-described studies, the safety profile of the FNA needles was excellent without any significant difference in complication rates.
Histology There are 2 limitations to EUS-guided FNA: (1) the diagnostic accuracy is impacted by the presence of an onsite cytopathologist to render diagnosis, and (2) certain neoplasms such as stromal cell tumors and lymphomas may be difficult to diagnose without histologic samples because their tissue architecture and morphology are essential for accurate pathologic assessment.6 Also, histologic tissue can provide a definitive diagnosis for benign diseases that may not always be possible with cytologic samples. To overcome these limitations and to improve diagnostic accuracy, a 19G Trucut needle biopsy (EUSTNB; Cook Endoscopy, Winston-Salem, NC) was developed to procure larger amounts of tissue with conserved architecture that would enable histologic analysis.6 The overall diagnostic accuracy of the EUS-TNB for evaluating suspicious lesions at various sites in the body is reported to be 75% to 84%7,8 and 61% to 67.5% for pancreatic masses.8,9 Although the EUS-TNB technique has some advantages over FNA, the rigidity induced by its 19G caliber and the mechanical friction of the firing mechanism produced by the torqued echoendoscope limits its use for evaluating pancreatic head and duodenal lesions.8,9 To overcome this limitation, a new 19G EUS-FNA device recently was
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developed (ProCore; Cook Endoscopy) with reverse bevel technology to enable the acquisition of core specimens for histologic analysis. In a large prospective study from Europe, histologic samples were obtained successfully with this new 19G FNB device in a majority of patients with diagnostic accuracy of more than 90%.10 However, some technical difficulties were encountered when performing transduodenal passes. The same FNB device also is available in a 22G platform to facilitate easy transduodenal sampling. The role of the standard 19G FNA needle for yielding histologic samples was assessed prospectively in a recent study.11 Of the 120 patients who underwent EUS-guided tissue acquisition, the procedure was technically successful in 119 patients (98.9%) and an adequate histologic sample was obtained in 116 patients (97.5%). A major limitation of the study was that patients with pancreatic head or uncinate masses were excluded. Because the standard 19G needle is too stiff to navigate the transduodenal route, a flexible 19G needle (Flex 19; Boston Scientific, Natick, MA) made of nitinol recently was introduced. Clinical studies evaluating its efficacy are currently underway.
Bottom Line Although the performance of the 22G and 25G needles is equivalent for FNA of all lesions including pancreatic body/ tail masses, because of its thin caliber, the 25G needle appears to be marginally better for sampling pancreatic head/uncinate lesions. A standard 19G or the 19G ProCore needle can procure histologic specimens in more than 90% of cases with the caveat that transduodenal sampling can be technically difficult.
Does Suction Have a Role in Endoscopic Ultrasound–Guided FineNeedle Aspiration? The role of suction at EUS-guided FNA remains debated. It is thought that suction, although increasing the quantity, diminishes the quality of an aspirate. Two randomized trials12,13 have attempted to address this issue and included FNA of lymph nodes and pancreatic masses (Table 2). In both trials, the use of suction did not improve the diagnostic yield of FNA. In one trial, the use of suction yielded better cellularity but did not improve the likelihood of obtaining a correct diagnosis.12
Figure 2. (A) The echoendoscope is in the long-scope position with an acutely angulated tip. This precludes free passage of the needle to deploy fiducials within a bile duct mass. (B) The echoendoscope is in the short-scope position with a straightened tip. The needle passage is much easier, facilitating fiducial placements within the bile duct mass.
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Table 1. Randomized Trials Comparing the Different Gauge Needles for EUS-Guided FNA of Solid Mass Lesions Study
Number
Camellini et al1
127
Fabbri et al2 Siddiqui et al3 Song et al4
50 131 117
Type of lesion
Needles
Diagnostic accuracy
Remarks
All lesions
22G vs 25G
77.8% vs 78.1%; P ⫽ NS
Pancreatic masses
22G vs 25G
86% vs 94%; P ⫽ NS
All lesions Pancreatic/peripancreatic masses
22G vs 25G 22G vs 19G
87.5% vs 95.5%, P ⫽ NS 78.9% vs 94.5%; P ⫽ .01
25G was better for uncinate masses and 22G was better for subepithelial masses Trend toward better yield with 25G — Technical success for FNA of pancreatic head masses was significantly less with the 19G needle. The 19G needle yielded significantly better cellular material
NS, not significant.
Bottom Line
Bottom Line
The use of suction at EUS-guided FNA yields specimens that are more bloody and without any improvement in diagnostic yield. For this reason, FNA of solid lesions or lymph nodes must be initiated without suction. If the aspirate obtained is scant, such as in chronic pancreatitis, then suction can be used to procure a better aspirate.
Are There Advantages to Use of a Stylet in Endoscopic Ultrasound–Guided Fine-Needle Aspiration? The presence of a stylet in an FNA assembly is to prevent the tip of the needle from being blocked by a plug of digestive wall tissue before entering the target lesion. However, the use of the stylet during individual FNA passes can be labor-intensive and may increase the risk of accidental needlestick injury. Three randomized trials14 –16 have evaluated the role of a stylet during EUS-guided FNA (Table 3). In all 3 trials, the use of a stylet did not improve the diagnostic yield for malignancy. In one study, the sample adequacy was better when a stylet was not used,14 and in all 3 trials the use of a stylet increased the bloodiness of the specimen. Table 2. Randomized Trials Evaluating the Role of Suction in EUS-Guided FNA Study Wallace et al12a Diagnostic yield Blood in specimen Cellularity Puri et al13b Diagnostic yield Blood in specimen Cellularity aFNA bFNA
Patients, n
Suction
No suction
P
43 Not improved More blood
Same No
.73 .0004
Better
Same
.01
52
of lymph node. of pancreatic mass.
92.3% 76.9% 100%
80% 88.5% 100%
.10 .14 1.0
There is no advantage to using a stylet during EUSFNA. The sample tends to be more bloody and without any difference in diagnostic yield. Because the FNA needle already is preloaded with a stylet, it is all right that the first pass be performed with a stylet but it should be removed for subsequent passes. However, the stylet should not be discarded because it is very useful for controlled expression of aspirates on to the slides.
Do Specific Maneuvers Improve the Diagnostic Yield of Endoscopic Ultrasound–Guided Fine-Needle Aspiration The center of a cancerous mass is usually more necrotic than the periphery and hence is more likely to yield nondiagnostic tissue when sampled.17 Therefore, to overcome this limitation, it has been suggested that aspiration of lesions at the periphery or in multiple areas may improve the diagnostic accuracy.18 Some endosonographers use a “fanning” technique Table 3. Randomized Trials Evaluating the Role of a Stylet in EUS-Guided FNA Study
No.
Sahai et al14 Sensitivity for malignancy Bloody specimen Sample adequacy Rastogi et al15 Minimal blood Diagnosis of malignancy ⬎50% cellularity Wani et al16 Minimal blood Diagnosis of malignancy ⬎50% cellularity
111
NS, not significant.
Stylet
No stylet
P
87%
83%
NS
75% 75%
52% 87%
⬍.0001 .01
50% 23%
41% 28%
.04 .29
15%
16%
NS
18.9% 38.7%
7.4% 36.1%
.02 .48
50%
45.9%
NS
101
162
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Figure 3. Illustration of the fanning technique of FNA in which the needle samples 4 different areas within a tumor mass.
of FNA, in which the needle is positioned at 4 different areas within a mass and then moved back and forth multiple times in each area to procure tissue (Supplementary Video 1). Sampling usually is initiated at the left margin of the tumor mass and then fanned until the right margin of the tumor is sampled (Figure 3) or multiple passes can be made in different areas of the mass to procure tissue. The trajectory of the needle can be altered using either the “up/down” endoscope dial or the elevator.
Bottom Line It appears that targeting the periphery of a mass as well as using the fanning principle is superior to the standard approach for EUS-guided FNA of pancreatic masses.
Does the Presence of an Onsite Cytopathologist Help? All studies published (Table 4) have shown that the presence of a cytopathologist during EUS-guided FNA improves diagnostic yield, decreases unsatisfactory samples, reduces the need for more passes, and, consequently, reduces the procedural duration.19 –21 In a recent study, 182 patients with pancreatic masses underwent EUS-guided FNA with (n ⫽ 95) or without (n ⫽ 87) an onsite cytopathologist.22 The presence of an onsite cytopathologist was associated with a significantly lower number of inadequate samples (1% vs 12.6%) and a higher diagnostic sensitivity (96.2% vs 78.2%). Also, a significantly higher number of needle passes was performed when an onsite cytopathologist was not available. In another study that compared the performance of a cytotechnician and an endoscopy
nurse for assessment of specimen adequacy, the rates of definitive diagnosis were significantly better and an inconclusive diagnosis occurred significantly less often when specimens were evaluated by a cytotechnician.23 In the United States, more than 50 advanced endoscopy fellows graduate annually with expertise in EUS. As the job market saturates in major metropolis and in academic medical centers, several of these novice endosonographers relocate to smaller cities where access to onsite cytopathology is limited. Despite being adequately trained, because of this limitation, their diagnostic yield at EUS-guided FNA suffers. Several steps can be undertaken to overcome this limitation. First, when an onsite cytopathologist is not available, most studies recommend that at least 3 passes be performed on lymph nodes and 6 to 7 passes on pancreatic masses to maximize the diagnostic yield.12,24,25 A dedicated pass must be performed for cell block should there be a need for additional studies such as flow cytometry or immunohistochemical staining. Second, procuring a histologic sample using a 19G or the reversely beveled needle can establish a diagnosis in more than 90% of patients.10,11 Third, every attempt must be made to obtain a high-quality specimen by adapting a fanning technique. Fourth, if possible, a trained cytotechnician must be used or the endosonographer should consider training himself or herself in the basics of cytopathology to ascertain specimen adequacy. Details on processing an FNA specimen is beyond the scope of this review. However, knowing the basic details is important to improve the outcomes of the procedure. In general, 2 types of smears can be prepared from the FNA specimen: air dried or alcohol fixed. Air dried smears are stained rapidly with DiffQuik (Dade Diagnostics, Miami, FL) and used for rapid onsite cytologic evaluation. Alcohol fixation preserves nuclear features and is stained by Papanicolaou or H&E stains. However, for lesions that may require special staining, cell block preparation is recommended. For cell block, the FNA specimen is placed into liquid media and sent to the laboratory where it is spun into a pellet, formalin-fixed, paraffin-embedded, and sectioned for standard H&E staining. Liquid-based cytology (Thin prep; Cytyc, Inc, Marlborough, MA, and SurePath; TriPath, Inc, Burlington, NC) is an automated process designed to minimize the technical problems associated with manual preparation. This method provides high cell preservation and uniform monolayer dispersion of cells into a confined area of the slide.26 However, disadvantages of this method include increased cost and inability to provide immediate cytologic assessment to the endosonographer unless the specimen is split into 2 parts, one for Diff-Quik and the other for liquid prep. This preparation also may lead to loss of background mucin, which is problematic because this is an important diagnostic clue for mucin-producing pancreatic tumors. In cases in which initial cytology is indeterminate, combining routine cytology with fluorescence in
Table 4. Select Studies Evaluating the Role of Onsite Cytopathology Service at EUS-Guided FNA Study
Patients, n
Diagnostic yield, OP vs no OP
Indeterminate samples, OP vs no OP
Unsatisfactory, OP vs no OP
Klapman et al19 Iglesias–Garcia et al22 Alsohaibani et al23
195 182 104
78% vs 32%, P ⫽ .001 97% vs 86%, P ⫽ .01 77% vs 53%, P ⫽ .01
10% vs 12%, P ⫽ .9 2.1% vs 10.3%, P ⫽ .02 23% vs 47%, P ⫽ .001
9% vs 20%, P ⫽ .003 1% vs 13%, P ⫽ .002 0% vs 17%, P ⫽ NS
OP, onsite pathology; NS, not significant.
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Table 5. Studies Evaluating the Value of Repeat EUS-Guided FNA Study
Proportion of repeat EUS-guided FNA cases
Indication
Diagnostic accuracy or impact
Eloubeidi et al29 DeWitt et al30 Nicaud et al31
24 of 517 (4.6%) pancreatic masses 73 of 8396 (0.8%) EUS examinations 30 of 3895 (0.77%) EUS examinations
Pancreatic masses 55% pancreatic masses Pancreatic masses
84% 63% 61%
situ hybridization and K-ras/p53 analysis may improve the diagnostic yield.27
Bottom Line The presence of an onsite cytopathologist or cytotechnician is a major determinant of diagnostic sensitivity in EUSFNA. If onsite cytopathology is not available, performing an adequate number of FNA passes using the fanning technique and procuring an additional specimen for histopathology/cell block can improve the diagnostic yield.
What if the Fine-Needle Aspiration Is Indeterminate? An FNA can be indeterminate even in the hands of an expert endosonographer. This is encountered more commonly when the following occurs: (1) performing an EUS-guided FNA of pancreatic mass lesions in the background of chronic pancreatitis, (2) if the lesion is in the uncinate process of the pancreas it may be difficult to visualize the lesion and/or obtain tissue, and (3) when cytology interpretation is indeterminate or difficult to interpret.28 In our experience, the diagnostic yield of EUS-guided FNA plateaus after 7 to 8 passes and then reaches a point of diminishing yield. Persisting with the procedure beyond this point yields a specimen that is mostly bloody and nondiagnostic. At present, there is no universally accepted protocol on how to manage patients with a high clinical suspicion for pancreatic cancer, but have negative cytology by EUS-guided FNA. The 3 most viable options are as follows: (1) clinical observation with repeat EUS-guided FNA in 2 to 4 months, (2) surgical exploration, or (3) CT-guided biopsy. CT-guided biopsy is less favorable owing to risk of seeding the needle track and causing a worse outcome even in patients who are not surgical candidates. If the suspicion of malignancy is very high and the patient is a good surgical candidate, and the lesion appears to be resectable, then the best option is often surgical resection. As the degree of suspicion for malignancy decreases, the health status of the patient is marginal, and the resectability is borderline, then repeat EUS-guided FNA is probably the best course of action. Also, if the patient or surgeon is reluctant to move forward with an open or laparoscopic exploration, then repeat EUS-guided FNA is a reasonable option. Three studies29 –31 have shown that a repeat EUS-guided FNA under such circumstances yields a correct diagnosis in 61% to 84% of patients (Table 5). Two of 3 studies comprised only of pancreatic masses and more than 50% of patients in another study also included pancreatic lesions. Also, combining fluorescence in situ hybridization and K-ras/p53 analysis may improve the diagnostic yield in such patients.27,32
Bottom Line The most common indication for repeat EUS-guided FNA is for evaluation of pancreatic masses. Performing a repeat
EUS guided-FNA (after a failed index procedure) in patients with high clinical suspicion of cancer appears to be a reasonable approach given the excellent safety profile of the procedure and a diagnostic accuracy of more than 60% under such circumstances.
Does Surgeon Experience Influence the Outcomes of a Procedure? Because FNAs of pancreatic masses are more technically challenging than other lesions, 2 studies have examined the learning curve of EUS-guided FNA in this patient cohort.33,34 In the first study of 57 patients with pancreatic mass lesions who underwent EUS-guided FNA by a self-taught endosonographer, the diagnostic sensitivities for malignancy from the first to last 10 quintiles were 30%, 40%, 70%, 90%, and 80%, respectively.33 In another study of 300 consecutive patients with pancreatic mass lesions who underwent EUS-guided FNA by an endosonographer with advanced endoscopy training, when the patients were divided into 3 groups (100 each), the median number of passes required to establish a diagnosis decreased significantly with surgeon experience.34 However, there was no significant difference in diagnostic accuracy between the 3 groups (group 1, 92%; group 2, 92%; group 3, 95%).
Bottom Line There certainly is a learning curve, at least, for EUSFNA of pancreatic masses. Although the diagnostic accuracy may plateau after a threshold number of procedures, the procedural expertise continues to improve with experience.
Are There Other Specific Recommendations to Optimize Endoscopic Ultrasound–Fine-Needle Aspiration Outcomes? Cyst Lesions Although uncommon, infection may develop secondary to aspiration of cystic lesions in the pancreas, mediastinum, and elsewhere.35 Performing multiple needle passes into a cyst appears to increase the risk of infection, as does failure to aspirate all the cyst fluid completely. It is recommended that prophylactic antibiotics be administered and continued for up to 48 hours for EUS-guided FNA of cyst lesions.36 In patients with complex cyst lesions in whom the clinical suspicion for malignancy is high, the solid component of the cyst must be aspirated for cytologic analysis. For the sake of efficiency, a 19G needle is most suited for performing cyst aspirations. However, if the cyst is small (⬍2 cm), a 22G needle may be used for aspiration. When aspirating a cyst, a change in echogenicity, from anechoic to hyperechoic, is indicative of intracystic hemorrhage.37 If this is observed, the procedure should be terminated and the patient monitored for hemodynamic stability for
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2 hours after the procedure. Clinically significant hemorrhage has not been reported in the literature and these incidences of intracystic bleeding almost always seem to be self-contained.
Conclusions In this review, we have attempted to provide a perspective on best practices in EUS-guided FNA. It is important to be cognizant that EUS-guided FNA is a multistep procedure. There is no one answer or single strategy to the different challenges that one encounters in clinical practice. However, by being attentive to the different steps involved and by adapting the best practices outlined in this review, one can expect to have optimal technical and clinical outcomes in a majority of their procedures.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at doi:10.1016/ j.cgh.2012.03.017. References 1. Camellini L, Carlinfante G, Azzolini F, et al. A randomized clinical trial comparing 22G and 25G needles in endoscopic ultrasoundguided fine-needle aspiration of solid lesions. Endoscopy 2011; 43:709 –715. 2. Fabbri C, Polifemo AM, Luigiano C, et al. Endoscopic ultrasoundguided fine needle aspiration with 22- and 25-gauge needles in solid pancreatic masses: a prospective comparative study with randomisation of needle sequence. Dig Liver Dis 2011;43:647– 652. 3. Siddiqui UD, Rossi F, Rosenthal LS, et al. EUS-guided FNA of solid pancreatic masses: a prospective, randomized trial comparing 22-gauge and 25-gauge needles. Gastrointest Endosc 2009;70: 1093–1097. 4. Song TJ, Kim JH, Lee SS, et al. The prospective randomized, controlled trial of endoscopic ultrasound-guided fine-needle aspiration using 22G and 19G aspiration needles for solid pancreatic or peripancreatic masses. Am J Gastroenterol 2010;105:1739 – 1745. 5. Sakamoto H, Kitano M, Komaki T, et al. Prospective comparative study of the EUS guided 25-gauge FNA needle with the 19-gauge trucut needle and 22-gauge FNA needle in patients with solid pancreatic masses. J Gastroenterol Hepatol 2009;24:384 –390. 6. Levy MJ. Endoscopic ultrasound-guided trucut biopsy of the pancreas: prospects and problems. Pancreatology 2007;7:163– 166. 7. Ginès A, Wiersema MJ, Clain JE, et al. Prospective study of a trucut needle for performing EUS-guided biopsy with EUS-guided FNA rescue. Gastrointest Endosc 2005;62:597– 601. 8. Thomas T, Kaye PV, Ragunath K, et al. Efficacy, safety, and predictive factors for a positive yield of EUS-guided Trucut biopsy: a large tertiary referral center experience. Am J Gastroenterol 2009;104:584 –591. 9. Larghi A, Verna EC, Stavropoulos SN, et al. EUS-guided trucut needle biopsies in patients with solid pancreatic masses: a prospective study. Gastrointest Endosc 2004;59:185–190. 10. Iglesias-Garcia J, Poley JW, Larghi A, et al. Feasibility and yield of a new EUS histology needle: results from a multicenter, pooled, cohort study. Gastrointest Endosc 2011;73:1189 –1196. 11. Larghi A, Verna EC, Ricci R, et al. EUS-guided fine-needle tissue acquisition by using a 19-gauge needle in a selected patient population: a prospective study. Gastrointest Endosc 2011;74: 504 –510.
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12. Wallace MB, Kennedy T, Durkalski V, et al. Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy. Gastrointest Endosc 2001;54:441– 447. 13. Puri R, Vilmann P, Sa ˘ ftoiu A, et al. Randomized controlled trial of endoscopic ultrasound-guided fine-needle sampling with or without suction for better cytological diagnosis. Scand J Gastroenterol 2009;44:499 –504. 14. Sahai AV, Paquin SC, Gariépy G. A prospective comparison of endoscopic ultrasound-guided fine needle aspiration results obtained in the same lesion, with and without the needle stylet. Endoscopy 2010;42:900 –903. 15. Rastogi A, Wani S, Gupta N, et al. A prospective, single-blind, randomized, controlled trial of EUS-guided FNA with and without a stylet. Gastrointest Endosc 2011;74:58 – 64. 16. Wani S, Gupta N, Gaddam S, et al. A comparative study of endoscopic ultrasound guided fine needle aspiration with and without a stylet. Dig Dis Sci 2011;56:2409 –2414. 17. Polkowski M, Larghi A, Weynand B, et al. Learning, techniques, and complications of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) technical guideline. Endoscopy 2012;44: 190 –206. 18. Ekberg O, Bergenfeldt M, Aspelin P, et al. Reliability of ultrasound-guided fine-needle biopsy of pancreatic masses. Acta Radiol 1988;29:535–539. 19. Klapman JB, Logrono R, Dye CE, et al. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration. Am J Gastroenterol 2003;98:1289 – 1294. 20. Chang KJ, Katz KD, Durbin TE, et al. Endoscopic ultrasoundguided fine-needle aspiration. Gastrointest Endosc 1994;40: 694 – 699. 21. Erickson RA, Sayage-Rabie L, Beissner RS. Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies. Gastrointest Endosc 2000;51:184 – 190. 22. Iglesias-Garcia J, Dominguez-Munoz JE, Abdulkader I, et al. Influence of on-site cytopathology evaluation on the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 2011; 106:1705–1710. 23. Alsohaibani F, Girgis S, Sandha GS. Does onsite cytotechnology evaluation improve the accuracy of endoscopic ultrasound-guided fine-needle aspiration biopsy? Can J Gastroenterol 2009;23: 26 –30. 24. LeBlanc JK, Ciaccia D, Al-Assi MT, et al. Optimal number of EUS-guided fine needle passes needed to obtain a correct diagnosis. Gastrointest Endosc 2004;59:475– 481. 25. Nguyen YP, Maple JT, Zhang Q, et al. Reliability of gross visual assessment of specimen adequacy during EUS-guided FNA of pancreatic masses. Gastrointest Endosc 2009;69:1264 –1270. 26. Lee KR, Papillo JL, St John T, et al. Evaluation of the ThinPrep processor for fine needle aspiration specimens. Acta Cytol 1996; 40:895– 899. 27. Reicher S, Boyar FZ, Albitar M, et al. Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses. Pancreas 2011;40:1057–1062. 28. Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc 2005;62:728 – 736. 29. Eloubeidi MA, Varadarajulu S, Desai S, et al. Value of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer. J Gastroenterol-Hepatol 2008;23: 567–570.
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30. DeWitt J, McGreevy K, Sherman S, et al. Utility of a repeated EUS at a tertiary-referral center. Gastrointest Endosc 2008;67:610 – 619. 31. Nicaud M, Hou W, Collins D, et al. The utility of repeat endoscopic ultrasound-guided fine needle aspiration for suspected pancreatic cancer. Gastroenterol Res Pract 2010;2010:268 – 290. 32. Kubiliun N, Ribeiro A, Fan YS, et al. EUS-FNA with rescue fluorescence in situ hybridization for the diagnosis of pancreatic carcinoma in patients with inconclusive on-site cytopathology results. Gastrointest Endosc 2011;74:541–547. 33. Mertz H, Gautam S. The learning curve for EUS-guided FNA of pancreatic cancer. Gastrointest Endosc 2004;59:33–37. 34. Eloubeidi MA, Tamhane A. EUS-guided FNA of solid pancreatic masses: a learning curve with 300 consecutive procedures. Gastrointest Endosc 2005;61:700 –708. 35. Annema JT, Veseliç M, Versteegh MI, et al. Mediastinitis caused by EUS-FNA of a bronchogenic cyst. Endoscopy 2003;35:791–793.
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36. Adler DG, Jacobson BC, Davila RE, et al. ASGE guideline: complications of EUS. Gastrointest Endosc 2005;61:8 –12. 37. Varadarajulu S, Eloubeidi MA. Frequency and significance of acute intracystic hemorrhage during EUS-FNA of cystic lesions of the pancreas. Gastrointest Endosc 2004;60:631– 635.
Reprint requests Address requests for reprints to: Shyam Varadarajulu, MD, Division of Gastroenterology-Hepatology, University of Alabama School of Medicine, JT 664, 625-19th Street S, Birmingham, Alabama 35249. e-mail: [email protected]; fax: (205) 975-6381. Conflicts of interest The authors disclose the following: all authors are consultants for Boston Scientific Corporation, Olympus Corporation.