Editorial
Endoscopic ultrasound-guided fine needle aspiration or fine needle biopsy: the beauty is in the eye of the beholder
Authors
Bronte Holt, Shyam Varadarajulu
Institution
Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA
submitted 8. July 2014 accepted 15. July 2014
The impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) on pancreatic tissue acquisition has been so profound that the technique is regarded as a disruptive innovation [1]. However, EUS-FNA has two major limitations: the diagnostic performance is dependent on the availability of a cytopathologist to render rapid onsite evaluation and it doesn’t provide histology, which may be required to establish a conclusive diagnosis when FNA cytology alone is insufficient. The ProCore biopsy needle was developed to overcome these limitations. In this issue of the journal, two randomized trials compare the diagnostic performance of the ProCore and standard FNA needles for tissue acquisition in solid pancreatic mass lesions [2, 3]. In the French multicenter study by Vanbiervliet et al., 80 patients with solid pancreatic masses underwent fine needle biopsy (FNB) using a single pass of the 22G ProCore needle and FNA with two passes of a standard 22G FNA needle, with the two investigations being performed in a randomized order [2]. The specimens were processed offsite for cytology and histology. There was no difference in diagnostic accuracy (> 90 % for both needles), and the overall histological quality was superior with the FNA needle. In the second study from South Korea by Lee et al., 116 patients with solid pancreatic masses were randomized to undergo either FNA or FNB using the ProCore or standard FNA needle, with 22G and 25G needles used in the stomach and duodenum respectively [3]. In addition to rapid onsite evaluation, each pass was analyzed for cytology and histology. Similar to the French multicenter study, there was no significant difference between the cohorts in overall diagnostic accuracy (FNB 98.3 % vs. FNA 94.8 %; P = 0.67) or histological accuracy (FNB 82.8 % vs. FNA 77.6 %; P = 0.64). Both randomized trials deliver the same message: the diagnostic performance of the ProCore and standard FNA needles are comparable. More im-
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377751 Endoscopy 2014; 46: 1046– 1048 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Shyam Varadarajulu, MD Center for Interventional Endoscopy Florida Hospital 601 East Rollins Street Orlando Florida 32803 USA Fax: +1 407 303 2585 [email protected]
Please see related articles from Vanbiervliet et al. p. 1063 and Lee et al. p. 1056
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
portantly, the histological yield of the ProCore needle is not superior to a standard FNA needle. A recent meta-analysis comparing the technical performance of the ProCore and standard FNA needles in 641 patients with pancreatic masses found no significant difference in the diagnostic accuracy between the ProCore and standard FNA needles (88.4 % [95 %CI 82.4 % – 93.3 %] vs. 79.9 % [95 %CI 73.6 % – 85.5 %], respectively; P = 0.067), or in terms of histological core tissue procurement (75.4 % [95 %CI 60.2 % – 87.8 %] vs. 75.2 % [95 %CI 63.2 % – 85.5 %], respectively; P = 0.075) [4]. These findings accord with the results of the two randomized trials published in this issue of the journal [2, 3]. In what context do we evaluate these findings and how do we move the discipline of EUS-guided tissue acquisition forward? The answers lie in a critical analysis of historical perspectives and lessons learnt from clinical experience, and reassessment of the technological refinements required to improve procedural outcomes.
Historical perspectives !
Percutaneous biopsy needles typically have a trucut, split, or core design to obtain a “slice” of the lesion. The advantage is that unlike a cytological aspirate, the procured specimen retains its morphological architecture, assisting histological interpretation. This may be important in the diagnosis of lesions such as well-differentiated adenocarcinoma, where the cytological aspirates tend to lack the typical hyperchromasia of malignancy, display minimal architectural disorder, and have only modestly increased nuclear–cytoplasmic ratios. Furthermore, hypocellular cytological aspirates, resulting in false-negative diagnoses, are more common. Most biopsy needles use a spring or sliding mechanism to “slice” through the targeted lesion,
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1046
Editorial
1047
Future directions
Fig. 1 Cytological aspirate from a pancreatic mass that was procured using the fanning maneuver demonstrating adenocarcinoma in association with severe fibrosis, and both normal and atypical ductal cells (Three-step stain; Richard-Allan Scientific, Kalamazoo, Michigan, USA; magnification × 200).
and tissue acquisition occurs during a single maneuver along one tissue plane. However, solid tumors are heterogeneous, with viable tumor cells interspersed between areas of necrosis and " Fig. 1). Procurement of tissue in tumor-associated fibrosis (● one plane cannot guarantee a diagnosis. The first endoscopic ultrasound (EUS)-compatible biopsy needle was developed in 2001 on a trucut platform. The overall diagnostic accuracy of the trucut biopsy needle for solid organ lesions is around 75 %. It has two significant design limitations. Firstly, its inherent stiffness precludes transduodenal sampling [5], restricting its use for lesions in the pancreatic body and tail. Secondly, unlike a standard hollow FNA needle that can be “fanned” in multiple trajectories through a mass, by virtue of its firing mechanism, the trucut platform only permits tissue acquisition in a single plane, resulting in a lower diagnostic yield. Bottom line: An EUS biopsy needle designed on a “cutting concept” that can also sample in multiple trajectories through a mass in a single pass is not available.
Technical evaluation !
The ProCore needle is available in three sizes: 19G, 22G, and 25G. It has a lateral opening with a reverse bevel near the tip of the needle shaft, into which tissue is suctioned, then cut and entrapped during needle withdrawal through the lesion. To overcome the limitations of the trucut design, the ProCore does not include a firing or sliding mechanism, which allows the needle to be “fanned” through a lesion. The histological yield of the 19G ProCore needle is 89.5 %, of the 22G needle is 82.8 %, and of the 25G needle is 63 % [5]; the 19G ProCore needle is the best for histology acquisition. But, in two recent studies, the standard and flexible 19G FNA needles also yielded histological tissue in more than 90 % of patients [7, 8]. When it comes to histology, it appears that needle size matters as much as needle design. However, the cumulative cytological yield for individual ProCore needles exceeds 90 % – 95 % when multiple passes are performed. In addition, the ProCore yields superior cellularity, which may enable a cytological diagnosis with fewer passes than standard FNA needles [3, 6]. Bottom line: Although the ProCore needle was originally designed to procure reliable histological samples, it yields better cytological aspirates than histological specimens.
After implementation of an EUS-FNA program at a tertiary referral center, the sensitivity and specificity for pancreatic cancer diagnosis improved from 55 % to 88 % and from 78 % and 96 %, respectively. There was a significant decline in diagnoses that were unsatisfactory (7 % vs. 1 %), atypical (16 % vs. 4 %), and suspicious (16 % vs. 3 %) [1]. EUS-FNA cytology has significantly improved diagnostic accuracy in pancreatic pathology, and has resulted in the displacement of techniques that yield a histological diagnosis [9]. The inability to reliably establish a histological diagnosis by percutaneous biopsy techniques was a significant driving force behind the development and increasing prominence of EUS-guided FNA cytology. Is it appropriate to take a concept that failed (percutaneous histological biopsy) and apply it to a technique (EUSFNA) that is near perfect? For EUS-guided cytology to be displaced, the outcomes of EUS-guided histology must be superior: a diagnostic accuracy and histological yield of greater than 95 %. Is this realistic? More importantly, how often do we really need histology? The authors perform 2500 EUS procedures annually, of which 45 % are FNAs, and core tissue is requested five times a year at most (0.4 %). The indications for FNB are finite. For diseases such as autoimmune pancreatitis and lymphoma, where core biopsy is preferred, we use a 19G needle. The specimen is collected in formalin or cell block for offsite evaluation; a histological diagnosis is reached in over 90 % of cases. In endoscopy, three factors are critical to drive a new concept forward: clinical need, the availability of technology, and cost-effectiveness. When evaluating pancreatic FNB, the clinical need remains undefined, the current technology is suboptimal, and the accessories are costly. If FNB is clinically important, we need to develop a needle that: (i) cuts to provide a tissue slice (preserved morphology), (ii) is flexible (fanning capability), and (iii) is of large caliber (adequate quantity). Such an accessory may yield a reliable high quality histology sample. Unless FNB replaces FNA to become the standard of care, the technique must be used only for indications where core histology is essential. Bottom line: If FNB is important to move the discipline of EUSguided tissue acquisition forward, we need to design a new biopsy needle with specific characteristics to attain that goal. The FNB devices may look different to the FNA needles, but there is no difference in their performance: the beauty is in the eye of the beholder. Competing interests: Shyam Varadarajulu is a consultant for Boston Scientific and for Olympus.
References 1 Eltoum IA, Alston EA, Roberson J. Trends in pancreatic pathology practice before and after implementation of endoscopic ultrasound-guided fine-needle aspiration. Arch Pathol Lab Med 2012; 136: 447 – 453 2 Vanbiervliet G, Napoléon B, Paul MCS et al. Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study. Endoscopy 2014: 1063 – 1070 3 Lee YN, Moon JH, Kim HK et al. Core biopsy needle versus standard aspiration needle for endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized parallel-group study. Endoscopy 2014: 1056 – 1062 4 Bang JY, Hasan M, Hawes R et al. EUS-guided tissue acquisition: metaanalysis comparing the procore and standard FNA needles. Gastrointest Endosc 2014; 79: AB427
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
!
Editorial 5 Panic N, Larghi A. Techniques for endoscopic ultrasound-guided fineneedle biopsy. Gastrointest Endosc Clin N Am 2014; 24: 83 – 107 6 Bang JY, Hebert-Magee S, Trevino J et al. Randomized trial comparing the 22-gauge aspiration and 22-gauge biopsy needles for EUS-guided sampling of solid pancreatic mass lesions. Gastrointest Endosc 2012; 76: 321 – 327 7 Larghi A, Capurso G, Carnuccio A et al. Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by
EUS-guided fine-needle tissue acquisition: a prospective study. Gastrointest Endosc 2012; 76: 570 – 577 8 Varadarajulu S, Bang JY, Hebert-Magee S. Assessment of the technical performance of the flexible 19-gauge EUS-FNA needle. Gastrointest Endosc 2012; 76: 336 – 343 9 Roy A, Kim M, Hawes RH et al. Changing trends in tissue acquisition in pancreatic diseases. Gastrointest Endosc 2013; 77: AB134
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1048
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
Copyright of Endoscopy is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Endoscopic ultrasound-guided fine needle aspiration or fine needle biopsy: the beauty is in the eye of the beholder
Authors
Bronte Holt, Shyam Varadarajulu
Institution
Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA
submitted 8. July 2014 accepted 15. July 2014
The impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) on pancreatic tissue acquisition has been so profound that the technique is regarded as a disruptive innovation [1]. However, EUS-FNA has two major limitations: the diagnostic performance is dependent on the availability of a cytopathologist to render rapid onsite evaluation and it doesn’t provide histology, which may be required to establish a conclusive diagnosis when FNA cytology alone is insufficient. The ProCore biopsy needle was developed to overcome these limitations. In this issue of the journal, two randomized trials compare the diagnostic performance of the ProCore and standard FNA needles for tissue acquisition in solid pancreatic mass lesions [2, 3]. In the French multicenter study by Vanbiervliet et al., 80 patients with solid pancreatic masses underwent fine needle biopsy (FNB) using a single pass of the 22G ProCore needle and FNA with two passes of a standard 22G FNA needle, with the two investigations being performed in a randomized order [2]. The specimens were processed offsite for cytology and histology. There was no difference in diagnostic accuracy (> 90 % for both needles), and the overall histological quality was superior with the FNA needle. In the second study from South Korea by Lee et al., 116 patients with solid pancreatic masses were randomized to undergo either FNA or FNB using the ProCore or standard FNA needle, with 22G and 25G needles used in the stomach and duodenum respectively [3]. In addition to rapid onsite evaluation, each pass was analyzed for cytology and histology. Similar to the French multicenter study, there was no significant difference between the cohorts in overall diagnostic accuracy (FNB 98.3 % vs. FNA 94.8 %; P = 0.67) or histological accuracy (FNB 82.8 % vs. FNA 77.6 %; P = 0.64). Both randomized trials deliver the same message: the diagnostic performance of the ProCore and standard FNA needles are comparable. More im-
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1377751 Endoscopy 2014; 46: 1046– 1048 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X Corresponding author Shyam Varadarajulu, MD Center for Interventional Endoscopy Florida Hospital 601 East Rollins Street Orlando Florida 32803 USA Fax: +1 407 303 2585 [email protected]
Please see related articles from Vanbiervliet et al. p. 1063 and Lee et al. p. 1056
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
portantly, the histological yield of the ProCore needle is not superior to a standard FNA needle. A recent meta-analysis comparing the technical performance of the ProCore and standard FNA needles in 641 patients with pancreatic masses found no significant difference in the diagnostic accuracy between the ProCore and standard FNA needles (88.4 % [95 %CI 82.4 % – 93.3 %] vs. 79.9 % [95 %CI 73.6 % – 85.5 %], respectively; P = 0.067), or in terms of histological core tissue procurement (75.4 % [95 %CI 60.2 % – 87.8 %] vs. 75.2 % [95 %CI 63.2 % – 85.5 %], respectively; P = 0.075) [4]. These findings accord with the results of the two randomized trials published in this issue of the journal [2, 3]. In what context do we evaluate these findings and how do we move the discipline of EUS-guided tissue acquisition forward? The answers lie in a critical analysis of historical perspectives and lessons learnt from clinical experience, and reassessment of the technological refinements required to improve procedural outcomes.
Historical perspectives !
Percutaneous biopsy needles typically have a trucut, split, or core design to obtain a “slice” of the lesion. The advantage is that unlike a cytological aspirate, the procured specimen retains its morphological architecture, assisting histological interpretation. This may be important in the diagnosis of lesions such as well-differentiated adenocarcinoma, where the cytological aspirates tend to lack the typical hyperchromasia of malignancy, display minimal architectural disorder, and have only modestly increased nuclear–cytoplasmic ratios. Furthermore, hypocellular cytological aspirates, resulting in false-negative diagnoses, are more common. Most biopsy needles use a spring or sliding mechanism to “slice” through the targeted lesion,
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1046
Editorial
1047
Future directions
Fig. 1 Cytological aspirate from a pancreatic mass that was procured using the fanning maneuver demonstrating adenocarcinoma in association with severe fibrosis, and both normal and atypical ductal cells (Three-step stain; Richard-Allan Scientific, Kalamazoo, Michigan, USA; magnification × 200).
and tissue acquisition occurs during a single maneuver along one tissue plane. However, solid tumors are heterogeneous, with viable tumor cells interspersed between areas of necrosis and " Fig. 1). Procurement of tissue in tumor-associated fibrosis (● one plane cannot guarantee a diagnosis. The first endoscopic ultrasound (EUS)-compatible biopsy needle was developed in 2001 on a trucut platform. The overall diagnostic accuracy of the trucut biopsy needle for solid organ lesions is around 75 %. It has two significant design limitations. Firstly, its inherent stiffness precludes transduodenal sampling [5], restricting its use for lesions in the pancreatic body and tail. Secondly, unlike a standard hollow FNA needle that can be “fanned” in multiple trajectories through a mass, by virtue of its firing mechanism, the trucut platform only permits tissue acquisition in a single plane, resulting in a lower diagnostic yield. Bottom line: An EUS biopsy needle designed on a “cutting concept” that can also sample in multiple trajectories through a mass in a single pass is not available.
Technical evaluation !
The ProCore needle is available in three sizes: 19G, 22G, and 25G. It has a lateral opening with a reverse bevel near the tip of the needle shaft, into which tissue is suctioned, then cut and entrapped during needle withdrawal through the lesion. To overcome the limitations of the trucut design, the ProCore does not include a firing or sliding mechanism, which allows the needle to be “fanned” through a lesion. The histological yield of the 19G ProCore needle is 89.5 %, of the 22G needle is 82.8 %, and of the 25G needle is 63 % [5]; the 19G ProCore needle is the best for histology acquisition. But, in two recent studies, the standard and flexible 19G FNA needles also yielded histological tissue in more than 90 % of patients [7, 8]. When it comes to histology, it appears that needle size matters as much as needle design. However, the cumulative cytological yield for individual ProCore needles exceeds 90 % – 95 % when multiple passes are performed. In addition, the ProCore yields superior cellularity, which may enable a cytological diagnosis with fewer passes than standard FNA needles [3, 6]. Bottom line: Although the ProCore needle was originally designed to procure reliable histological samples, it yields better cytological aspirates than histological specimens.
After implementation of an EUS-FNA program at a tertiary referral center, the sensitivity and specificity for pancreatic cancer diagnosis improved from 55 % to 88 % and from 78 % and 96 %, respectively. There was a significant decline in diagnoses that were unsatisfactory (7 % vs. 1 %), atypical (16 % vs. 4 %), and suspicious (16 % vs. 3 %) [1]. EUS-FNA cytology has significantly improved diagnostic accuracy in pancreatic pathology, and has resulted in the displacement of techniques that yield a histological diagnosis [9]. The inability to reliably establish a histological diagnosis by percutaneous biopsy techniques was a significant driving force behind the development and increasing prominence of EUS-guided FNA cytology. Is it appropriate to take a concept that failed (percutaneous histological biopsy) and apply it to a technique (EUSFNA) that is near perfect? For EUS-guided cytology to be displaced, the outcomes of EUS-guided histology must be superior: a diagnostic accuracy and histological yield of greater than 95 %. Is this realistic? More importantly, how often do we really need histology? The authors perform 2500 EUS procedures annually, of which 45 % are FNAs, and core tissue is requested five times a year at most (0.4 %). The indications for FNB are finite. For diseases such as autoimmune pancreatitis and lymphoma, where core biopsy is preferred, we use a 19G needle. The specimen is collected in formalin or cell block for offsite evaluation; a histological diagnosis is reached in over 90 % of cases. In endoscopy, three factors are critical to drive a new concept forward: clinical need, the availability of technology, and cost-effectiveness. When evaluating pancreatic FNB, the clinical need remains undefined, the current technology is suboptimal, and the accessories are costly. If FNB is clinically important, we need to develop a needle that: (i) cuts to provide a tissue slice (preserved morphology), (ii) is flexible (fanning capability), and (iii) is of large caliber (adequate quantity). Such an accessory may yield a reliable high quality histology sample. Unless FNB replaces FNA to become the standard of care, the technique must be used only for indications where core histology is essential. Bottom line: If FNB is important to move the discipline of EUSguided tissue acquisition forward, we need to design a new biopsy needle with specific characteristics to attain that goal. The FNB devices may look different to the FNA needles, but there is no difference in their performance: the beauty is in the eye of the beholder. Competing interests: Shyam Varadarajulu is a consultant for Boston Scientific and for Olympus.
References 1 Eltoum IA, Alston EA, Roberson J. Trends in pancreatic pathology practice before and after implementation of endoscopic ultrasound-guided fine-needle aspiration. Arch Pathol Lab Med 2012; 136: 447 – 453 2 Vanbiervliet G, Napoléon B, Paul MCS et al. Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study. Endoscopy 2014: 1063 – 1070 3 Lee YN, Moon JH, Kim HK et al. Core biopsy needle versus standard aspiration needle for endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized parallel-group study. Endoscopy 2014: 1056 – 1062 4 Bang JY, Hasan M, Hawes R et al. EUS-guided tissue acquisition: metaanalysis comparing the procore and standard FNA needles. Gastrointest Endosc 2014; 79: AB427
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
!
Editorial 5 Panic N, Larghi A. Techniques for endoscopic ultrasound-guided fineneedle biopsy. Gastrointest Endosc Clin N Am 2014; 24: 83 – 107 6 Bang JY, Hebert-Magee S, Trevino J et al. Randomized trial comparing the 22-gauge aspiration and 22-gauge biopsy needles for EUS-guided sampling of solid pancreatic mass lesions. Gastrointest Endosc 2012; 76: 321 – 327 7 Larghi A, Capurso G, Carnuccio A et al. Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by
EUS-guided fine-needle tissue acquisition: a prospective study. Gastrointest Endosc 2012; 76: 570 – 577 8 Varadarajulu S, Bang JY, Hebert-Magee S. Assessment of the technical performance of the flexible 19-gauge EUS-FNA needle. Gastrointest Endosc 2012; 76: 336 – 343 9 Roy A, Kim M, Hawes RH et al. Changing trends in tissue acquisition in pancreatic diseases. Gastrointest Endosc 2013; 77: AB134
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
1048
Holt, Bronte, Varadarajulu, Shyam. EUS-guided FNA or FNB … Endoscopy 2014; 46: 1046–1048
Copyright of Endoscopy is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
