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A prospective, single-blind, randomized, controlled trial of EUS-guided FNA with and without a stylet
ORIGINAL ARTICLE: Clinical Endoscopy
A prospective, single-blind, randomized, controlled trial of EUS-guided FNA with and without a stylet Amit Rastogi, MD, Sachin Wani, MD, Neil Gupta, MD, Vikas Singh, MD, Srinivas Gaddam, MD, Savio Reddymasu, MD, Ozlem Ulusarac, MD, Fang Fan, MD, Maria Romanas, MD, Katie L. Dennis, MD, Prateek Sharma, MD, Ajay Bansal, MD, Melissa Oropeza-Vail, RN, Mojtaba Olyaee, MD Kansas City, Kansas, USA
Background: Most endosonographers use an EUS needle with an internal stylet during EUS-guided FNA (EUS-FNA). Reinserting the stylet into the needle after every pass is tedious and time-consuming, and there are no data to suggest that it improves the quality of the cytology specimen. Objective: To compare the samples obtained by EUS-FNA with and without a stylet for (1) the degree of cellularity, adequacy, contamination, and amount of blood and (2) the diagnostic yield of malignancy. Design: Prospective,single-blind, randomized, controlled trial. Setting: Two tertiary care referral centers. Patients: Patients referred for EUS-FNA of solid lesions. Intervention: Patients underwent EUS-FNA of the solid lesions, and 2 passes each were made with a stylet and without a stylet in the needle. The order of the passes was randomized, and the cytopathologists reviewing the slides were blinded to the stylet status of passes. Main Outcome Measurements: Degree of cellularity, adequacy, contamination, amount of blood, and the diagnostic yield of malignancy in the specimens. Results: A total of 101 patients with 118 lesions were included in final analysis; 236 FNA passes were made, each with and without a stylet. No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), contamination (P ⫽ .92), or significant amount of blood (P ⫽ .61) between specimens obtained with and without a stylet. The diagnostic yield of malignancy was 55 of 236 specimens (23%) in the with-stylet group compared with 66 of 236 specimens (28%) in the without-stylet group (P ⫽ .29). Limitations: Endosonographers were not blinded to the stylet status of the passes. Conclusions: Using a stylet during EUS-FNA does not confer any significant advantage with regard to the quality of the specimen obtained or the diagnostic yield of malignancy. (Clinical trial registration number: NCT 01213290). (Gastrointest Endosc 2011;74:58-64.)
EUS and EUS-guided FNA (EUS-FNA) have emerged as safe and accurate modalities for the diagnosis and staging of GI and certain non-GI malignancies.1 Real-time tissue sampling by EUS-FNA can provide expedited diagnostic and prognostic information relating to the presence or
absence of malignancy, as well as the staging.2,3 Several factors can affect the diagnostic yield and accuracy of EUS-FNA such as the skill and experience of the endosonographer, the presence of an on-site cytopathologist, the diameter of the needle, the use of suction during
Abbreviation: EUS-FNA, EUS-guided FNA.
(A.R., S.W., N.G., S.R., F.F., K.L.D., P.S., A.B., M.O.-V., M.O.), Kansas City, Kansas, USA.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright © 2011 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2011.02.015
Presented at the Annual Scientific Meeting of the American College of Gastroenterology, 2010, San Antonio, Tex.
Received December 13, 2010. Accepted February 16, 2011.
Reprint requests: Amit Rastogi, MD, University of Kansas School of Medicine, Gastroenterology (111), Kansas City Veterans Affairs Medical Center, 4801 E. Linwood Blvd., Kansas City, MO 64128-2295.
Current affiliations: Veterans Affairs Medical Center (A.R., S.W., N.G., V.S., S.G., S.R., O.U., M.R., P.S., A.B.), University of Kansas School of Medicine
If you would like to chat with an author of this article, you may contact Dr. Rastogi at [email protected].
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FNA, and the number of passes.4-10 Conventionally, most endosonographers use an EUS needle with an internal stylet during EUS-FNA. The use of this removable stylet is based on the theoretical belief that it helps prevent clogging of the lumen of the needle by the GI wall tissue as the needle traverses this to reach the target lesion. Blockage of the needle with gut wall tissue can impair the ability to aspirate cells from the target lesion and thus negatively affect the quality and the diagnostic yield of the specimen obtained by EUS-FNA. Although this assumption favoring the use of a stylet seems logical, there is no concrete evidence supporting its use during EUS-FNA. Moreover, the use of a stylet is labor-intensive and time-consuming and makes the procedure more tedious because the stylet must be withdrawn after puncturing the lesion and then reinserted into the needle before the next pass.11 The aims of this study were to compare the samples obtained by EUS-FNA with and without a stylet for (1) the degree of cellularity, adequacy, contamination, and amount of blood and (2) the diagnostic yield of malignancy.
METHODS Design This was a prospective, single-blind, randomized, controlled trial conducted at 2 tertiary care referral centers. The study was approved by the local institutional review board at both centers.
Randomized, controlled trial of EUS-FNA with and without a stylet
Take-home Message ●
●
This randomized, controlled trial showed no significant differences between the specimens obtained by EUS-FNA with and without a stylet with regard to cellularity, adequacy of the specimen, contamination, significant amount of blood, and diagnostic yield of malignancy. If these findings are confirmed by other studies, then the use of a stylet can be avoided during EUS-FNA.
size, shape, margins (regular, irregular, well defined, poorly defined), and echogenicity of the lesions were recorded on a case report form. After localizing the lesion, a 22-gauge needle (EUS N-3; Cook Medical, Winston Salem, NC) was used for EUS-FNA. For the passes made with a stylet, the latter was left inside the needle, slightly retracted from the tip. After puncturing the lesion, the stylet was pushed in beyond the needle tip and then removed. If the next pass was also designated to be with the stylet, then it was reinserted in the needle. For passes made without a stylet, there was no stylet in the needle throughout that entire pass. For all passes, the needle was passed through the GI tract wall into the lesion followed by approximately 10 to 12 backward and forward movements while keeping the needle tip in the lesion. Continuous suction using a 10-mL syringe was applied. This was turned off before withdrawing the needle from the lesion.
Study population Patients referred for EUS-FNA of solid lesions were prospectively enrolled in this study. Patients were enrolled from August 2009 to May 2010. Written informed consent was obtained from all patients. The inclusion criteria were age older than 18 years, ability to provide informed consent, and the presence of a solid lesion-like mediastinal or intra-abdominal lymph nodes or mass, solid pancreatic mass, left adrenal mass, GI submucosal lesion, or liver lesion confirmed by at least a single investigational modality like CT, magnetic resonance imaging, and endoscopy. The exclusion criteria were severe coagulopathy (international normalized ratio ⬎1.5) or thrombocytopenia (platelet count ⬍50,000), inability to sample the lesion because of the presence of intervening blood vessels, results of EUS-FNA would not affect patient management, and the inability to provide informed consent.
Randomization Each lesion was sampled for a minimum of 4 needle passes: 2 passes with a stylet in place and 2 without a stylet. The order of these passes was determined by a preprinted randomization sequence kept in an opaque sealed envelope that was opened by a research coordinator after enrollment.
Cytopathology
All procedures were performed by 2 experienced endosonographers (A.R. and M.O.). The curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus Medical Systems, Center Valley, Pa, or EG-3630U; Pentax, Montvale, NJ) were used. The procedures were performed with the patients in the left lateral position under moderate sedation with intravenous midazolam and intravenous meperidine or fentanyl or intravenous propofol. The location,
Each procedure was performed with a cytopathologist or cytotechnologist in the room. After each pass, the sample from the needle was expressed using a 10-mL air-filled syringe onto a glass slide until no further material could be expressed. Then using another glass slide, the sample was spread out to make 2 slides. These slides were numbered according to the number of the pass. One slide was air dried and stained with Diff-Quik stain for immediate onsite interpretation. The other slide was fixed in alcohol (95% ethanol) and stained later with Papanicolaou stain. The residual contents of the needle after every pass were flushed with 5 to 10 mL of sterile saline solution into the Saccomano or cytolyte solution. After flushing the needle, the exterior of the needle was wiped with sterile gauze soaked in saline solution to reduce cross-contamination between the passes. There was no communication between the endosonographer and the cytopathologist regarding the ade-
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TABLE 1. Cytological results of samples obtained with and without stylet
Parameter
With a stylet (n ⴝ 236)
Without a stylet (n ⴝ 236)
P value
Cellularity % area of slide that contains cells of the representative lesion
.97
No representative cells present
74 (31%)
70 (30%)
Representative cells present in ⬍25% of the slide
84 (36%)
84 (35%)
Representative cells present in ⬍25%-50% of the slide
42 (18%)
45 (19%)
Representative cells present in ⬎50 % of the slide
36 (15%)
37 (16%)
No. of cells per slide
.99
Fair (⬍100 cells/slide)
116 (49%)
118 (50%)
Good (100-1000 cells/slide)
73 (31%)
72 (31%)
Excellent (⬎1000 cells/slide)
46 (20%)
46 (19%)
Adequacy of specimen
.26
Inadequate
102 (43%)
89 (38%)
Adequate
133 (57%)
146 (62%)
Contamination % area of slide that represents GI contamination
.92
No contaminations seen
83 (35%)
79 (33%)
Contamination present in ⬍25% of the slide
115 (49%)
122 (52%)
Contamination present in 25%-50% of the slide
32 (14%)
30 (13%)
6 (2%)
5 (2%)
Minimal
119 (50%)
96 (41%)
.04
Moderate
78 (33%)
105 (45%)
.01
Significant
39 (17%)
34 (14%)
.61
Contamination present in ⬎50% of the slide Amount of blood
Diagnosis
.75
Benign
38 (16%)
41 (17%)
Atypical
28 (12%)
24 (10%)
Suspicious
18 (8%)
18 (8%)
Malignant
55 (23%)
66 (28%)
Inadequate for reporting
97 (41%)
87 (37%)
quacy of the specimen or diagnosis until all 4 passes had been completed. The on-site evaluation of smears was performed to assess cellular adequacy and to assess the need for any additional passes, ie, after the first 4 passes. The cytology slides were evaluated by 4 cytopathologists who were all blinded to the stylet status of the passes. All of the slides from 1 patient were evaluated by 1 cytopathologist. The slides for each pass were assessed using strict predefined criteria for the following (Table 1): cellu-
larity, adequacy of the specimen, contamination, amount of blood, and diagnosis. These criteria were agreed on by consensus of the 4 cytopathologists and were described previously.12 The final diagnosis of malignancy was made by reviewing all of the slides prepared from the lesion by passes made with and without the stylet, any additional passes, as well as from the cell block. The results were entered on a case report form and then transferred to an ACCESS database.
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Randomized, controlled trial of EUS-FNA with and without a stylet
Figure 1. Enrollment of patients.
Outcome variables The primary outcome of this study was the degree of cellularity, adequacy, contamination, and amount of blood in the samples obtained by EUS-FNA with and without the stylet. The secondary outcome was the diagnostic yield of malignancy in the specimens obtained by EUS-FNA with and without stylet.
categorical data when 2 outcomes were possible. A 2-sided P value ⬍.05 was considered significant. The results are reported in accordance to the CONSORT 2010 statement13 and Standards for Reporting of Diagnostic Accuracy (STARD) Guidelines.14
RESULTS
Statistical analysis
Patients and lesions
A target sample size of 100 patients was decided a priori. Lack of good prospective data comparing the 2 techniques (EUS-FNA with and without stylet) precluded us from making formal assumptions to calculate a valid sample size. We assumed that a sample size of 100 patients would provide enough pilot data that can be used to conduct larger multicenter, randomized trials in the future. If EUS-FNA was performed on more than 1 lesion in a patient, then for statistical analysis, these lesions were considered as independent observations. The statistical software program STATA/IC version 10.1 (StataCorp, College Station, Tex) was used for analysis. The Fisher exact test was used to compare categorical variables for analysis based on individual FNA passes such as degree of cellularity, contamination, amount of blood, adequacy of sample, and final diagnosis. McNemar’s test was used to compare paired
A total of 109 patients were enrolled from August 2009 to May 2010 (Fig. 1). Eight patients were excluded; 6 patients took their cytology slides for review to another institution before they could be reviewed for the study and 2 patients underwent only 3 FNA passes. Of the 101 patients included in this analysis, 70 (69%) were males, 86 (85%) were white, 11 (11%) were African Americans, and 4 (4%) were Hispanics. The mean age was 63.1 years (standard deviation 13.8). A total of 118 lesions underwent EUS-FNA: 61 pancreatic masses (52%), 31 lymph nodes (26%), 6 liver lesions (5%), 5 left adrenal masses (4%), and 15 others (13%) (1 submucosal lesion in the esophagus, 4 gastric submucosal lesions, 1 rectal submucosal lesion, 2 ampullary masses, 5 peripancreatic or porta hepatis masses, 1 right lung mass, 1 retroperitoneal mass). The mean size of the lesions was 2.75 cm (standard deviation
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1.8 cm). The shape of the lesions was irregular in 43 (36%), round in 36 (31%), oval in 34 (29%), and triangular in 5 (4%). The margins of the lesions were regular in 70 (59%) and irregular in 48 (41%). A total of 89 lesions (75%) were hypoechoic. The final cytological diagnosis was malignant in 55 lesions (47%), suspicious for malignancy in 8 lesions (6%), atypical cells in 15 lesions (13%), benign in 27 lesions (23%), and inadequate sample in 13 lesions (11%). In all lesions, at least 2 passes were made with a stylet and 2 without a stylet. Hence, a total of 236 passes with a stylet were compared with 236 passes made without a stylet. There were no instances of needle malfunction or clogging reported during this study.
Cytopathology No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), contamination (P ⫽ 0.92), and significant amount of blood (P ⫽ .61) between the specimens obtained with and without a stylet (Table 1). The EUS-FNA with-stylet group had a higher proportion of specimens with minimal amount of blood (P ⫽ .04) and a lower proportion of specimens with a moderate amount of blood (P ⫽ .01) compared with EUS-FNA without a stylet. Diagnostic yield of malignancy was 55 of 236 specimens (23%) in the with-stylet group compared with 66 of 236 specimens (28%) in the without-stylet group (P ⫽ .29). Similarly, if specimens diagnosed as suspicious for malignancy were included in the malignant group, then also there was no significant difference seen between the 2 groups (with stylet: 73/236 [31%] vs without stylet: 84/236 [36%], P ⫽ .33). A final diagnosis of malignancy was made in 55 of 118 lesions (47%). Per-lesion analysis shows that in the withstylet group, diagnosis of malignancy was made in 35 of these 55 lesions (64%), whereas in the without-stylet group, it was made in 43 of these 55 lesions (78%) (P ⫽ .13). Therefore, 20 malignant lesions (36%) were missed by the with-stylet passes, whereas only 12 (22%) were missed by the without-stylet passes. This difference was not statistically significant (P ⫽ .13). Twenty-eight of the 55 malignant lesions (51%) were diagnosed as malignant by both EUS-FNA techniques. Of the 20 malignant lesions missed by the with-stylet passes, 14 were pancreatic cancers, 2 were malignant lymph nodes, and 4 were others. Of the 12 malignant lesions missed by the without-stylet passes, 6 were pancreatic cancers, 2 were malignant lymph nodes, and 4 were others. If the lesions diagnosed as suspicious for malignancy were included in the malignant category, then a total of 63 of 118 lesions (53%) would be deemed malignant. Of these, 49 lesions (78%) would have been diagnosed in the with-stylet group, whereas 50 (80%) would have been diagnosed in the without-stylet group (P ⫽ 1.00). Therefore, 14 malignant/suspicious lesions were missed by the withstylet passes and 13 were missed by the without-stylet 62 GASTROINTESTINAL ENDOSCOPY Volume 74, No. 1 : 2011
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passes. Forty-two of these lesions were diagnosed as malignant or suspicious by both techniques. Furthermore, we compared the cellularity, adequacy of the specimen, contamination, amount of blood, and diagnostic yield of malignancy between the specimens obtained with and without a stylet from different types of lesions, ie, pancreas, lymph nodes, and others. For the 61 pancreatic masses, there were no significant differences seen in the cellularity (P ⫽ .26), adequacy of the specimen (P ⫽ .23), contamination (P ⫽ .58), significant amount of blood (P ⫽ 1.0), and diagnostic yield of malignancy (P ⫽ .30) between 122 specimens obtained each with and without a stylet. Similarly, for lymph nodes, there were no significant differences seen in the cellularity (P ⫽ .35), adequacy of the specimen (P ⫽ .85), contamination (P ⫽ .75), significant amount of blood (P ⫽ .68), and the diagnostic yield of malignancy (P ⫽ .69) between the specimens obtained with and without a stylet. Last, for the rest of the lesions combined, there were also no significant differences seen in the cellularity (P ⫽ .93), adequacy of the specimen (P ⫽ .44), contamination (P ⫽ .50), significant amount of blood (P ⫽ .78), and the diagnostic yield of malignancy (P ⫽ .78) between the specimens obtained with and without a stylet.
DISCUSSION EUS-FNA is being increasingly used for the diagnosis and staging of both GI and non-GI malignancies. Although the technique of EUS-FNA and the type of needle used varies between different endosonographers, most still use a stylet in the needle. The use of a stylet is based on conventional wisdom that it improves the quality of specimens obtained and hence the diagnostic yield. This is based on the premise that a stylet prevents clogging of the lumen of the needle by the GI wall tissue as the needle traverses this. There are, however, no data to suggest that the use of a stylet is beneficial in any way. Moreover, there are several disadvantages to using a stylet. Reinserting the stylet in the needle after every pass is time-consuming, tedious, and cumbersome for the technician assisting with the procedure. It may also increase the risk of unintentional needle stick injury. In certain situations, it may be difficult, if not impossible, to advance or remove the stylet once the target lesion has been punctured, especially if there is a loop in the echoendoscope, the needle is bent, or a 19-gauge needle is being used. Reinserting the stylet in the needle can become increasingly difficult with each pass if there is a kink or a bend in the needle sheath. We conducted a prospective, single-blind, randomized, controlled trial to compare the specimens obtained by EUS-FNA with and without a stylet for the degree of cellularity, adequacy, contamination, amount of blood, and diagnostic yield of malignancy. All slides were reviewed by cytopathologists who were blinded to the stylet status. A total of 236 passes each were made with and www.giejournal.org
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without a stylet in 118 lesions. The cytological characteristics were compared using well-defined comprehensive criteria. No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), and contamination (P ⫽ .92) between specimens obtained with and without a stylet. EUS-FNA in the without-stylet group had a lower proportion of specimens with minimal amount of blood and a higher proportion of specimens with a moderate amount of blood compared with the with-stylet group. However, there was no difference in the significant amount of blood (P ⫽ .61) between specimens obtained by the 2 techniques. Although the diagnostic yield of malignancy was higher in the passes made without a stylet by 14%, the difference was not statistically significant (P ⫽ .13). Our results thus challenge the premise that using a stylet during EUS-FNA improves the quality or diagnostic yield of specimen obtained. There are limited data comparing EUS-FNA with and without a stylet. In a recent study, Sahai et al11 compared the yield of malignancy and quality of the specimens obtained during EUS-FNA with and without a stylet. A total of 135 lesions in 111 patients were sampled by a single endosonographer using a 22-gauge needle with a systematic assignment of with and without stylet passes in a 1:2 ratio. All slides in this study were read by a single, blinded cytopathologist for bloodiness, adequacy, and presence of malignancy. The proportion of adequate samples was lower (75% vs 87%, P ⫽ .013) and the proportion of bloody samples higher (75% vs 52%, P ⫽ .0001) in the with-stylet group compared with the without-stylet group. Therefore, in this study, the use of a stylet was actually associated with an inferior sample quality. In 46 lesions in which an equal number of passes was made with and without a stylet, the yield for malignancy was similar in the 2 techniques. The investigators thus questioned the value and utility of using a stylet during EUS-FNA. Because this study used the needles manufactured by Olympus, the conclusions appear to be valid for needles from different manufacturers. Another retrospective study, still in abstract form,15 compared the yield and number of passes required to obtain adequate samples among cases with and without a stylet. A total of 54 sites in 47 consecutive patients were sampled with a 25-gauge needle, and no differences were seen in the cellularity, contamination, and diagnostic yield in the 2 techniques. In an earlier study from our institution,12 we retrospectively compared the quality of the specimens and the diagnostic yield of malignancy between samples obtained with and without a stylet. EUSFNA procedures were performed with a stylet (106 lesions) and without a stylet (122 lesions) in 2 different time periods. The slides were retrieved, de-identified, and evaluated by 2 cytopathologists blinded to the FNA technique. No significant differences were seen in the 2 techniques in the cellularity (P ⫽ .37), contamination (P ⫽ .18), significant amount of blood (P ⫽ .42), and adequacy of the specimen (P ⫽ .45). Furthermore, the diagnostic yield of www.giejournal.org
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malignancy was not different (P ⫽ .48). Another prospective study, still in abstract form,16 in 37 patients with pancreatic mass showed no difference in the adequacy of the specimen obtained with and without a stylet. Thus, there is growing evidence suggesting the futility of using a stylet during EUS-FNA, whereas there are no data to support its use. Our study has a few limitations. Although we used very comprehensive, predefined criteria to assess the cytological characteristics of the specimens obtained with and without a stylet, there remains subjectivity in their assessment by the cytopathologists. However, all of the slides from 1 patient were evaluated by 1 cytopathologist who was blinded to the stylet status of the passes. Hence, all cytopathologists evaluated equal numbers of slides obtained by the 2 techniques. We did not assess for the interobserver agreement among the cytopathologists in the assessment of EUS-FNA specimens. Only 22-gauge needles were used in this study, and hence the results may not be generalizable to needles of other sizes (19 or 25 gauge). Continuous suction was used for all passes, and this may have affected the amount of blood. The endosonographers were not blinded to the stylet status of each pass, as logistically this was not possible. Deliberate efforts were made, however, to ensure that apart from the use of a stylet, there was no difference in the technique for each of the 4 passes made in the lesion. We did not follow the patients longitudinally to address the issue of sensitivity, specificity, and accuracy of the 2 techniques in detecting malignancy. In conclusion, this prospective, randomized, controlled, single-blind study shows that using a stylet during EUS-FNA does not confer any significant advantage with regard to the quality of the specimen obtained or the diagnostic yield of malignancy. If these results are confirmed by endosonographers at other centers, it would be reasonable not to use a stylet during EUS-FNA, potentially making the procedure less tedious and more efficient.
REFERENCES 1. Erickson RA. EUS-guided FNA. Gastrointest Endosc 2004;60:267-79. 2. Kulesza P, Eltoum IA. Endoscopic ultrasound-guided fine-needle aspiration: sampling, pitfalls, and quality management. Clin Gastroenterol Hepatol 2007;5:1248-54. 3. Bardales RH, Stelow EB, Mallery S, et al. Review of endoscopic ultrasound-guided fine-needle aspiration cytology. Diagn Cytopathol 2006;34:140-75. 4. Mertz H, Gautam S. The learning curve for EUS-guided FNA of pancreatic cancer. Gastrointest Endosc 2004;59:33-7. 5. 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;98:1289-94. 6. 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;70:1093-7. 7. Yusuf TE, Ho S, Pavey DA, et al. Retrospective analysis of the utility of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in
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8.
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pancreatic masses, using a 22-gauge or 25-gauge needle system: a multicenter experience. Endoscopy 2009;41:445-8. 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 and peripancreatic masses. Am J Gastroenterol 2010;105:1739-45. Puri R, Vilmann P, Saftoiu 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. 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: 441-7. Sahai AV, Paquin SC, Gariepy 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;42:900-3.
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12. Wani SB, Gupta N, Gaddam S, et al. Is the use of stylet during endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) worth the effort? A comparative study of EUS-FNA with and without a stylet [abstract]. Gastrointest Endosc 2010;71:AB286. 13. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010;152:726-32. 14. Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003;326:41-4. 15. Devicente N, Hawes R, Hoffman B, et al. The yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is not affected by leaving out the stylet [abstract]. Gastrointest Endosc 2009;69:AB335. 16. Chin MW, Coss A, Mcloughlin M, et al. Stylet use does not affect adequacy of specimen of pancreatic EUS FNA: a prospective, single blinded, randomized, control trial [abstract]. Gastrointest Endosc 2010:71:AB285.
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A prospective, single-blind, randomized, controlled trial of EUS-guided FNA with and without a stylet Amit Rastogi, MD, Sachin Wani, MD, Neil Gupta, MD, Vikas Singh, MD, Srinivas Gaddam, MD, Savio Reddymasu, MD, Ozlem Ulusarac, MD, Fang Fan, MD, Maria Romanas, MD, Katie L. Dennis, MD, Prateek Sharma, MD, Ajay Bansal, MD, Melissa Oropeza-Vail, RN, Mojtaba Olyaee, MD Kansas City, Kansas, USA
Background: Most endosonographers use an EUS needle with an internal stylet during EUS-guided FNA (EUS-FNA). Reinserting the stylet into the needle after every pass is tedious and time-consuming, and there are no data to suggest that it improves the quality of the cytology specimen. Objective: To compare the samples obtained by EUS-FNA with and without a stylet for (1) the degree of cellularity, adequacy, contamination, and amount of blood and (2) the diagnostic yield of malignancy. Design: Prospective,single-blind, randomized, controlled trial. Setting: Two tertiary care referral centers. Patients: Patients referred for EUS-FNA of solid lesions. Intervention: Patients underwent EUS-FNA of the solid lesions, and 2 passes each were made with a stylet and without a stylet in the needle. The order of the passes was randomized, and the cytopathologists reviewing the slides were blinded to the stylet status of passes. Main Outcome Measurements: Degree of cellularity, adequacy, contamination, amount of blood, and the diagnostic yield of malignancy in the specimens. Results: A total of 101 patients with 118 lesions were included in final analysis; 236 FNA passes were made, each with and without a stylet. No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), contamination (P ⫽ .92), or significant amount of blood (P ⫽ .61) between specimens obtained with and without a stylet. The diagnostic yield of malignancy was 55 of 236 specimens (23%) in the with-stylet group compared with 66 of 236 specimens (28%) in the without-stylet group (P ⫽ .29). Limitations: Endosonographers were not blinded to the stylet status of the passes. Conclusions: Using a stylet during EUS-FNA does not confer any significant advantage with regard to the quality of the specimen obtained or the diagnostic yield of malignancy. (Clinical trial registration number: NCT 01213290). (Gastrointest Endosc 2011;74:58-64.)
EUS and EUS-guided FNA (EUS-FNA) have emerged as safe and accurate modalities for the diagnosis and staging of GI and certain non-GI malignancies.1 Real-time tissue sampling by EUS-FNA can provide expedited diagnostic and prognostic information relating to the presence or
absence of malignancy, as well as the staging.2,3 Several factors can affect the diagnostic yield and accuracy of EUS-FNA such as the skill and experience of the endosonographer, the presence of an on-site cytopathologist, the diameter of the needle, the use of suction during
Abbreviation: EUS-FNA, EUS-guided FNA.
(A.R., S.W., N.G., S.R., F.F., K.L.D., P.S., A.B., M.O.-V., M.O.), Kansas City, Kansas, USA.
DISCLOSURE: All authors disclosed no financial relationships relevant to this publication. Copyright © 2011 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2011.02.015
Presented at the Annual Scientific Meeting of the American College of Gastroenterology, 2010, San Antonio, Tex.
Received December 13, 2010. Accepted February 16, 2011.
Reprint requests: Amit Rastogi, MD, University of Kansas School of Medicine, Gastroenterology (111), Kansas City Veterans Affairs Medical Center, 4801 E. Linwood Blvd., Kansas City, MO 64128-2295.
Current affiliations: Veterans Affairs Medical Center (A.R., S.W., N.G., V.S., S.G., S.R., O.U., M.R., P.S., A.B.), University of Kansas School of Medicine
If you would like to chat with an author of this article, you may contact Dr. Rastogi at [email protected].
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FNA, and the number of passes.4-10 Conventionally, most endosonographers use an EUS needle with an internal stylet during EUS-FNA. The use of this removable stylet is based on the theoretical belief that it helps prevent clogging of the lumen of the needle by the GI wall tissue as the needle traverses this to reach the target lesion. Blockage of the needle with gut wall tissue can impair the ability to aspirate cells from the target lesion and thus negatively affect the quality and the diagnostic yield of the specimen obtained by EUS-FNA. Although this assumption favoring the use of a stylet seems logical, there is no concrete evidence supporting its use during EUS-FNA. Moreover, the use of a stylet is labor-intensive and time-consuming and makes the procedure more tedious because the stylet must be withdrawn after puncturing the lesion and then reinserted into the needle before the next pass.11 The aims of this study were to compare the samples obtained by EUS-FNA with and without a stylet for (1) the degree of cellularity, adequacy, contamination, and amount of blood and (2) the diagnostic yield of malignancy.
METHODS Design This was a prospective, single-blind, randomized, controlled trial conducted at 2 tertiary care referral centers. The study was approved by the local institutional review board at both centers.
Randomized, controlled trial of EUS-FNA with and without a stylet
Take-home Message ●
●
This randomized, controlled trial showed no significant differences between the specimens obtained by EUS-FNA with and without a stylet with regard to cellularity, adequacy of the specimen, contamination, significant amount of blood, and diagnostic yield of malignancy. If these findings are confirmed by other studies, then the use of a stylet can be avoided during EUS-FNA.
size, shape, margins (regular, irregular, well defined, poorly defined), and echogenicity of the lesions were recorded on a case report form. After localizing the lesion, a 22-gauge needle (EUS N-3; Cook Medical, Winston Salem, NC) was used for EUS-FNA. For the passes made with a stylet, the latter was left inside the needle, slightly retracted from the tip. After puncturing the lesion, the stylet was pushed in beyond the needle tip and then removed. If the next pass was also designated to be with the stylet, then it was reinserted in the needle. For passes made without a stylet, there was no stylet in the needle throughout that entire pass. For all passes, the needle was passed through the GI tract wall into the lesion followed by approximately 10 to 12 backward and forward movements while keeping the needle tip in the lesion. Continuous suction using a 10-mL syringe was applied. This was turned off before withdrawing the needle from the lesion.
Study population Patients referred for EUS-FNA of solid lesions were prospectively enrolled in this study. Patients were enrolled from August 2009 to May 2010. Written informed consent was obtained from all patients. The inclusion criteria were age older than 18 years, ability to provide informed consent, and the presence of a solid lesion-like mediastinal or intra-abdominal lymph nodes or mass, solid pancreatic mass, left adrenal mass, GI submucosal lesion, or liver lesion confirmed by at least a single investigational modality like CT, magnetic resonance imaging, and endoscopy. The exclusion criteria were severe coagulopathy (international normalized ratio ⬎1.5) or thrombocytopenia (platelet count ⬍50,000), inability to sample the lesion because of the presence of intervening blood vessels, results of EUS-FNA would not affect patient management, and the inability to provide informed consent.
Randomization Each lesion was sampled for a minimum of 4 needle passes: 2 passes with a stylet in place and 2 without a stylet. The order of these passes was determined by a preprinted randomization sequence kept in an opaque sealed envelope that was opened by a research coordinator after enrollment.
Cytopathology
All procedures were performed by 2 experienced endosonographers (A.R. and M.O.). The curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus Medical Systems, Center Valley, Pa, or EG-3630U; Pentax, Montvale, NJ) were used. The procedures were performed with the patients in the left lateral position under moderate sedation with intravenous midazolam and intravenous meperidine or fentanyl or intravenous propofol. The location,
Each procedure was performed with a cytopathologist or cytotechnologist in the room. After each pass, the sample from the needle was expressed using a 10-mL air-filled syringe onto a glass slide until no further material could be expressed. Then using another glass slide, the sample was spread out to make 2 slides. These slides were numbered according to the number of the pass. One slide was air dried and stained with Diff-Quik stain for immediate onsite interpretation. The other slide was fixed in alcohol (95% ethanol) and stained later with Papanicolaou stain. The residual contents of the needle after every pass were flushed with 5 to 10 mL of sterile saline solution into the Saccomano or cytolyte solution. After flushing the needle, the exterior of the needle was wiped with sterile gauze soaked in saline solution to reduce cross-contamination between the passes. There was no communication between the endosonographer and the cytopathologist regarding the ade-
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TABLE 1. Cytological results of samples obtained with and without stylet
Parameter
With a stylet (n ⴝ 236)
Without a stylet (n ⴝ 236)
P value
Cellularity % area of slide that contains cells of the representative lesion
.97
No representative cells present
74 (31%)
70 (30%)
Representative cells present in ⬍25% of the slide
84 (36%)
84 (35%)
Representative cells present in ⬍25%-50% of the slide
42 (18%)
45 (19%)
Representative cells present in ⬎50 % of the slide
36 (15%)
37 (16%)
No. of cells per slide
.99
Fair (⬍100 cells/slide)
116 (49%)
118 (50%)
Good (100-1000 cells/slide)
73 (31%)
72 (31%)
Excellent (⬎1000 cells/slide)
46 (20%)
46 (19%)
Adequacy of specimen
.26
Inadequate
102 (43%)
89 (38%)
Adequate
133 (57%)
146 (62%)
Contamination % area of slide that represents GI contamination
.92
No contaminations seen
83 (35%)
79 (33%)
Contamination present in ⬍25% of the slide
115 (49%)
122 (52%)
Contamination present in 25%-50% of the slide
32 (14%)
30 (13%)
6 (2%)
5 (2%)
Minimal
119 (50%)
96 (41%)
.04
Moderate
78 (33%)
105 (45%)
.01
Significant
39 (17%)
34 (14%)
.61
Contamination present in ⬎50% of the slide Amount of blood
Diagnosis
.75
Benign
38 (16%)
41 (17%)
Atypical
28 (12%)
24 (10%)
Suspicious
18 (8%)
18 (8%)
Malignant
55 (23%)
66 (28%)
Inadequate for reporting
97 (41%)
87 (37%)
quacy of the specimen or diagnosis until all 4 passes had been completed. The on-site evaluation of smears was performed to assess cellular adequacy and to assess the need for any additional passes, ie, after the first 4 passes. The cytology slides were evaluated by 4 cytopathologists who were all blinded to the stylet status of the passes. All of the slides from 1 patient were evaluated by 1 cytopathologist. The slides for each pass were assessed using strict predefined criteria for the following (Table 1): cellu-
larity, adequacy of the specimen, contamination, amount of blood, and diagnosis. These criteria were agreed on by consensus of the 4 cytopathologists and were described previously.12 The final diagnosis of malignancy was made by reviewing all of the slides prepared from the lesion by passes made with and without the stylet, any additional passes, as well as from the cell block. The results were entered on a case report form and then transferred to an ACCESS database.
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Randomized, controlled trial of EUS-FNA with and without a stylet
Figure 1. Enrollment of patients.
Outcome variables The primary outcome of this study was the degree of cellularity, adequacy, contamination, and amount of blood in the samples obtained by EUS-FNA with and without the stylet. The secondary outcome was the diagnostic yield of malignancy in the specimens obtained by EUS-FNA with and without stylet.
categorical data when 2 outcomes were possible. A 2-sided P value ⬍.05 was considered significant. The results are reported in accordance to the CONSORT 2010 statement13 and Standards for Reporting of Diagnostic Accuracy (STARD) Guidelines.14
RESULTS
Statistical analysis
Patients and lesions
A target sample size of 100 patients was decided a priori. Lack of good prospective data comparing the 2 techniques (EUS-FNA with and without stylet) precluded us from making formal assumptions to calculate a valid sample size. We assumed that a sample size of 100 patients would provide enough pilot data that can be used to conduct larger multicenter, randomized trials in the future. If EUS-FNA was performed on more than 1 lesion in a patient, then for statistical analysis, these lesions were considered as independent observations. The statistical software program STATA/IC version 10.1 (StataCorp, College Station, Tex) was used for analysis. The Fisher exact test was used to compare categorical variables for analysis based on individual FNA passes such as degree of cellularity, contamination, amount of blood, adequacy of sample, and final diagnosis. McNemar’s test was used to compare paired
A total of 109 patients were enrolled from August 2009 to May 2010 (Fig. 1). Eight patients were excluded; 6 patients took their cytology slides for review to another institution before they could be reviewed for the study and 2 patients underwent only 3 FNA passes. Of the 101 patients included in this analysis, 70 (69%) were males, 86 (85%) were white, 11 (11%) were African Americans, and 4 (4%) were Hispanics. The mean age was 63.1 years (standard deviation 13.8). A total of 118 lesions underwent EUS-FNA: 61 pancreatic masses (52%), 31 lymph nodes (26%), 6 liver lesions (5%), 5 left adrenal masses (4%), and 15 others (13%) (1 submucosal lesion in the esophagus, 4 gastric submucosal lesions, 1 rectal submucosal lesion, 2 ampullary masses, 5 peripancreatic or porta hepatis masses, 1 right lung mass, 1 retroperitoneal mass). The mean size of the lesions was 2.75 cm (standard deviation
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1.8 cm). The shape of the lesions was irregular in 43 (36%), round in 36 (31%), oval in 34 (29%), and triangular in 5 (4%). The margins of the lesions were regular in 70 (59%) and irregular in 48 (41%). A total of 89 lesions (75%) were hypoechoic. The final cytological diagnosis was malignant in 55 lesions (47%), suspicious for malignancy in 8 lesions (6%), atypical cells in 15 lesions (13%), benign in 27 lesions (23%), and inadequate sample in 13 lesions (11%). In all lesions, at least 2 passes were made with a stylet and 2 without a stylet. Hence, a total of 236 passes with a stylet were compared with 236 passes made without a stylet. There were no instances of needle malfunction or clogging reported during this study.
Cytopathology No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), contamination (P ⫽ 0.92), and significant amount of blood (P ⫽ .61) between the specimens obtained with and without a stylet (Table 1). The EUS-FNA with-stylet group had a higher proportion of specimens with minimal amount of blood (P ⫽ .04) and a lower proportion of specimens with a moderate amount of blood (P ⫽ .01) compared with EUS-FNA without a stylet. Diagnostic yield of malignancy was 55 of 236 specimens (23%) in the with-stylet group compared with 66 of 236 specimens (28%) in the without-stylet group (P ⫽ .29). Similarly, if specimens diagnosed as suspicious for malignancy were included in the malignant group, then also there was no significant difference seen between the 2 groups (with stylet: 73/236 [31%] vs without stylet: 84/236 [36%], P ⫽ .33). A final diagnosis of malignancy was made in 55 of 118 lesions (47%). Per-lesion analysis shows that in the withstylet group, diagnosis of malignancy was made in 35 of these 55 lesions (64%), whereas in the without-stylet group, it was made in 43 of these 55 lesions (78%) (P ⫽ .13). Therefore, 20 malignant lesions (36%) were missed by the with-stylet passes, whereas only 12 (22%) were missed by the without-stylet passes. This difference was not statistically significant (P ⫽ .13). Twenty-eight of the 55 malignant lesions (51%) were diagnosed as malignant by both EUS-FNA techniques. Of the 20 malignant lesions missed by the with-stylet passes, 14 were pancreatic cancers, 2 were malignant lymph nodes, and 4 were others. Of the 12 malignant lesions missed by the without-stylet passes, 6 were pancreatic cancers, 2 were malignant lymph nodes, and 4 were others. If the lesions diagnosed as suspicious for malignancy were included in the malignant category, then a total of 63 of 118 lesions (53%) would be deemed malignant. Of these, 49 lesions (78%) would have been diagnosed in the with-stylet group, whereas 50 (80%) would have been diagnosed in the without-stylet group (P ⫽ 1.00). Therefore, 14 malignant/suspicious lesions were missed by the withstylet passes and 13 were missed by the without-stylet 62 GASTROINTESTINAL ENDOSCOPY Volume 74, No. 1 : 2011
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passes. Forty-two of these lesions were diagnosed as malignant or suspicious by both techniques. Furthermore, we compared the cellularity, adequacy of the specimen, contamination, amount of blood, and diagnostic yield of malignancy between the specimens obtained with and without a stylet from different types of lesions, ie, pancreas, lymph nodes, and others. For the 61 pancreatic masses, there were no significant differences seen in the cellularity (P ⫽ .26), adequacy of the specimen (P ⫽ .23), contamination (P ⫽ .58), significant amount of blood (P ⫽ 1.0), and diagnostic yield of malignancy (P ⫽ .30) between 122 specimens obtained each with and without a stylet. Similarly, for lymph nodes, there were no significant differences seen in the cellularity (P ⫽ .35), adequacy of the specimen (P ⫽ .85), contamination (P ⫽ .75), significant amount of blood (P ⫽ .68), and the diagnostic yield of malignancy (P ⫽ .69) between the specimens obtained with and without a stylet. Last, for the rest of the lesions combined, there were also no significant differences seen in the cellularity (P ⫽ .93), adequacy of the specimen (P ⫽ .44), contamination (P ⫽ .50), significant amount of blood (P ⫽ .78), and the diagnostic yield of malignancy (P ⫽ .78) between the specimens obtained with and without a stylet.
DISCUSSION EUS-FNA is being increasingly used for the diagnosis and staging of both GI and non-GI malignancies. Although the technique of EUS-FNA and the type of needle used varies between different endosonographers, most still use a stylet in the needle. The use of a stylet is based on conventional wisdom that it improves the quality of specimens obtained and hence the diagnostic yield. This is based on the premise that a stylet prevents clogging of the lumen of the needle by the GI wall tissue as the needle traverses this. There are, however, no data to suggest that the use of a stylet is beneficial in any way. Moreover, there are several disadvantages to using a stylet. Reinserting the stylet in the needle after every pass is time-consuming, tedious, and cumbersome for the technician assisting with the procedure. It may also increase the risk of unintentional needle stick injury. In certain situations, it may be difficult, if not impossible, to advance or remove the stylet once the target lesion has been punctured, especially if there is a loop in the echoendoscope, the needle is bent, or a 19-gauge needle is being used. Reinserting the stylet in the needle can become increasingly difficult with each pass if there is a kink or a bend in the needle sheath. We conducted a prospective, single-blind, randomized, controlled trial to compare the specimens obtained by EUS-FNA with and without a stylet for the degree of cellularity, adequacy, contamination, amount of blood, and diagnostic yield of malignancy. All slides were reviewed by cytopathologists who were blinded to the stylet status. A total of 236 passes each were made with and www.giejournal.org
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without a stylet in 118 lesions. The cytological characteristics were compared using well-defined comprehensive criteria. No significant differences were seen in the cellularity (P ⫽ .98), adequacy of the specimen (P ⫽ .26), and contamination (P ⫽ .92) between specimens obtained with and without a stylet. EUS-FNA in the without-stylet group had a lower proportion of specimens with minimal amount of blood and a higher proportion of specimens with a moderate amount of blood compared with the with-stylet group. However, there was no difference in the significant amount of blood (P ⫽ .61) between specimens obtained by the 2 techniques. Although the diagnostic yield of malignancy was higher in the passes made without a stylet by 14%, the difference was not statistically significant (P ⫽ .13). Our results thus challenge the premise that using a stylet during EUS-FNA improves the quality or diagnostic yield of specimen obtained. There are limited data comparing EUS-FNA with and without a stylet. In a recent study, Sahai et al11 compared the yield of malignancy and quality of the specimens obtained during EUS-FNA with and without a stylet. A total of 135 lesions in 111 patients were sampled by a single endosonographer using a 22-gauge needle with a systematic assignment of with and without stylet passes in a 1:2 ratio. All slides in this study were read by a single, blinded cytopathologist for bloodiness, adequacy, and presence of malignancy. The proportion of adequate samples was lower (75% vs 87%, P ⫽ .013) and the proportion of bloody samples higher (75% vs 52%, P ⫽ .0001) in the with-stylet group compared with the without-stylet group. Therefore, in this study, the use of a stylet was actually associated with an inferior sample quality. In 46 lesions in which an equal number of passes was made with and without a stylet, the yield for malignancy was similar in the 2 techniques. The investigators thus questioned the value and utility of using a stylet during EUS-FNA. Because this study used the needles manufactured by Olympus, the conclusions appear to be valid for needles from different manufacturers. Another retrospective study, still in abstract form,15 compared the yield and number of passes required to obtain adequate samples among cases with and without a stylet. A total of 54 sites in 47 consecutive patients were sampled with a 25-gauge needle, and no differences were seen in the cellularity, contamination, and diagnostic yield in the 2 techniques. In an earlier study from our institution,12 we retrospectively compared the quality of the specimens and the diagnostic yield of malignancy between samples obtained with and without a stylet. EUSFNA procedures were performed with a stylet (106 lesions) and without a stylet (122 lesions) in 2 different time periods. The slides were retrieved, de-identified, and evaluated by 2 cytopathologists blinded to the FNA technique. No significant differences were seen in the 2 techniques in the cellularity (P ⫽ .37), contamination (P ⫽ .18), significant amount of blood (P ⫽ .42), and adequacy of the specimen (P ⫽ .45). Furthermore, the diagnostic yield of www.giejournal.org
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malignancy was not different (P ⫽ .48). Another prospective study, still in abstract form,16 in 37 patients with pancreatic mass showed no difference in the adequacy of the specimen obtained with and without a stylet. Thus, there is growing evidence suggesting the futility of using a stylet during EUS-FNA, whereas there are no data to support its use. Our study has a few limitations. Although we used very comprehensive, predefined criteria to assess the cytological characteristics of the specimens obtained with and without a stylet, there remains subjectivity in their assessment by the cytopathologists. However, all of the slides from 1 patient were evaluated by 1 cytopathologist who was blinded to the stylet status of the passes. Hence, all cytopathologists evaluated equal numbers of slides obtained by the 2 techniques. We did not assess for the interobserver agreement among the cytopathologists in the assessment of EUS-FNA specimens. Only 22-gauge needles were used in this study, and hence the results may not be generalizable to needles of other sizes (19 or 25 gauge). Continuous suction was used for all passes, and this may have affected the amount of blood. The endosonographers were not blinded to the stylet status of each pass, as logistically this was not possible. Deliberate efforts were made, however, to ensure that apart from the use of a stylet, there was no difference in the technique for each of the 4 passes made in the lesion. We did not follow the patients longitudinally to address the issue of sensitivity, specificity, and accuracy of the 2 techniques in detecting malignancy. In conclusion, this prospective, randomized, controlled, single-blind study shows that using a stylet during EUS-FNA does not confer any significant advantage with regard to the quality of the specimen obtained or the diagnostic yield of malignancy. If these results are confirmed by endosonographers at other centers, it would be reasonable not to use a stylet during EUS-FNA, potentially making the procedure less tedious and more efficient.
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pancreatic masses, using a 22-gauge or 25-gauge needle system: a multicenter experience. Endoscopy 2009;41:445-8. 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 and peripancreatic masses. Am J Gastroenterol 2010;105:1739-45. Puri R, Vilmann P, Saftoiu 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. 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: 441-7. Sahai AV, Paquin SC, Gariepy 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;42:900-3.
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12. Wani SB, Gupta N, Gaddam S, et al. Is the use of stylet during endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) worth the effort? A comparative study of EUS-FNA with and without a stylet [abstract]. Gastrointest Endosc 2010;71:AB286. 13. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 2010;152:726-32. 14. Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. BMJ 2003;326:41-4. 15. Devicente N, Hawes R, Hoffman B, et al. The yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is not affected by leaving out the stylet [abstract]. Gastrointest Endosc 2009;69:AB335. 16. Chin MW, Coss A, Mcloughlin M, et al. Stylet use does not affect adequacy of specimen of pancreatic EUS FNA: a prospective, single blinded, randomized, control trial [abstract]. Gastrointest Endosc 2010:71:AB285.
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