Int J Gastrointest Interv 2022; 11(3): 96-101
Published online July 31, 2022 https://doi.org/10.18528/ijgii220019
Copyright © International Journal of Gastrointestinal Intervention.
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Correspondence to:*Division of Gastroenterology, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
E-mail address: firstname.lastname@example.org (W.H. Paik).
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Endoscopic ultrasound (EUS)-guided tissue acquisition is an established method for the pathologic diagnosis of solid pancreatic masses due to its high accuracy and safety. Currently, EUS-guided biopsy is applied to any lesions adjacent to the gastrointestinal tract that can be visualized with EUS. In this review, conventional and novel types of needles for EUS-guided tissue acquisition are introduced and their diagnostic performance is compared. In addition, technical issues and sampling handling methods to improve diagnostic accuracy are discussed.
Keywords: Biopsy, Diagnosis, Instrumentation, Needles, Pathology
Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is a pivotal method for the pathologic diagnosis of solid pancreatic masses due to its high accuracy and safety.1 EUS-FNAB is now applied to any lesions adjacent to the gastrointestinal tract that can be visualized with EUS. In the past, only cytological evaluations were performed through EUS-guided fine needle aspiration (EUS-FNA), but some lesions require an evaluation of tissue architecture, including immunohistochemical staining, for an accurate pathologic assessment.2 For pancreatic neuroendocrine tumors, it is important to obtain a histologic core to determine the mitosis count and Ki-67 index, which are important prognostic factors.3 Therefore, various types of needles have been developed to obtain adequate core tissue samples to conduct a further histologic evaluation and improve the diagnostic yield.4–8 In addition, many techniques and devices for EUS-guided tissue acquisition and handling methods of obtained tissue have been introduced, and clinical studies have been conducted to prove their efficacy.9–11 Methods for the on-site evaluation of sample adequacy, such as rapid on-site evaluation (ROSE) by a cytopathologist and macroscopic on-site evaluation (MOSE) by an endoscopist, have been introduced to confirm whether an obtained sample is adequate for interpretation, and several supplementary methods have also been introduced in sample handling to increase sample adequacy.12,13 In this review, various types of needles for EUS-guided tissue acquisition, sampling techniques for better diagnostic yield, and methods for processing obtained samples are discussed.
At first, all EUS-FNA needles had a similar basic design for a cytopathological diagnosis only. About a decade ago, new needles designed to obtain core tissue with preserved tissue architecture for histologic evaluations and molecular profiling were developed.14 The names of the biopsy needles currently in use and their features are described in Table 1. By using a biopsy needle, it is theoretically possible to obtain a core tissue sample that can be identified by gross inspection, which is expected to reduce the number of needle passes and increase the diagnostic yield without ROSE. However, in real-world clinical practice, the shape and material of the aspiration needle have been developed together, so that sufficient core tissue can also be obtained with the aspiration needle. Since reverse-bevel biopsy needles showed only minimal benefits in tissue acquisition, antegrade-bevel biopsy needles were introduced to obtain a larger amount of tissue because they hold the tissue while pushing the needle forward, which is the most effective movement during the procedure.15 Biopsy needles showed better diagnostic adequacy and accuracy, with fewer needle passes in solid gastrointestinal lesions, but not in solid pancreatic lesions.16 Franseen and fork-tip biopsy needles have been compared in a meta-analysis, which found that both Franseen and fork-tip needles demonstrated a similarly high diagnostic yield of over 90%, with comparable adverse events.17
Table 1 . A List of Needles for EUS-Guided Tissue Acquisition.
|Product||Company||Shape||Needle size (gauge)|
|ProCore||Cook||Menghini-tip with core trap||19, 20, 22, 25|
|Acquire||Boston Scientific||Franseen||22, 25|
|EZ Shot 3 Plus||Olympus||Menghini-tip with side hole||19, 22|
|SharkCore||Medtronic||Fork-tip||19, 22, 25|
EUS, endoscopic ultrasound..
Interestingly, a recent meta-analysis compared the accuracy of needles in solid pancreatic masses according to the needle shape.18 In 16 randomized controlled trials with 1,934 patients, Franseen, Menghini-tip, reverse-bevel, antegrade-bevel, and fork-tip needles were compared with respect to the diagnostic performance using FNA as reference values. Among them, Franseen and fork-tip needles, particularly those of a 22-gauge size, showed the best results in diagnostic accuracy and sample adequacy.
Regarding needle size, a systematic review with a network meta-analysis was performed, and no specific gauge was superior among 19-, 22-, and 25-gauge needles in terms of diagnostic accuracy, sample adequacy, and histologic core procurement; however, these results were based on low-quality evidence.19 Nonetheless, 25-gauge needles seem to be more convenient to handle, and they are especially useful when there is acute angulation to access the lesion, as is the case for lesions in the uncinate process or medial aspect of the pancreas head.20 A previous meta-analysis suggested that 25-gauge needles were more sensitive than 22-gauge needles for diagnosing solid pancreatic masses because 25-gauge needles retrieve less bloody aspirate and show better handling in needle passage and actuation.20 However, in real clinical practice, when 25-gauge needles are used, it is often not easy to push out the obtained tissue by reinserting the stylet. In addition, recent developments in needles have made them more flexible, and the advantages of the 25-gauge needle have been diluted because the diagnosis is usually made based on a biopsy specimen rather than cytology. The use of 19-gauge needles is limited because of their stiffness, but these large-bore needles seem to be useful for establishing organoids with tissues obtained through EUS or performing molecular profiling for precision medicine.
New needle concepts, including EUS-guided through-the-needle (TTN) microforceps and confocal laser endomicroscopy (CLE), have been introduced.21–25 These devices are usually used for the diagnosis of pancreatic cysts, for which conventional EUS-FNA and cyst fluid analysis have low diagnostic yield.26 The major limitations of EUS-FNA result from obtaining insufficient fluid for biochemical analysis and inadequate sample cellularity.27,28
TTN biopsy demonstrated a higher diagnostic yield for pancreatic cysts than EUS-FNA; however, concerns about safety issues have been raised, including bleeding, leakage, infection, and pancreatitis.29,30 A recent multicenter retrospective analysis of 506 patients who underwent TTN biopsy with microforceps revealed that the incidence of adverse events was 11.5%, and intraductal papillary mucinous neoplasms sampled with multiple microforceps passes were classified as being at high risk for adverse events (28%).31 Therefore, the risk-benefit balance of TTN biopsy should be carefully considered, and TTN biopsy should be performed in selected patients.
Needle-based CLE allows for a real-time
TTN biopsy and CLE were compared in the diagnosis of pancreatic cysts, and CLE showed higher diagnostic yield than biopsy (85% vs. 74%,
Endoscopists have adopted diverse techniques to improve the diagnostic accuracy of EUS-guided tissue acquisition, and numerous studies have tried to determine the ideal techniques for EUS-guided tissue acquisition. The following technical factors can be considered in EUS-FNAB: suction or non-suction, applying capillary sampling with a stylet slow-pull, the number of to-and-fro movements or actuations, the door-knocking technique, the fanning technique, the torque technique, the number of needle passes, and the use of a stylet.39–41
The basic maneuvers in EUS-FNAB are as follows. The echoendoscope should be positioned as straight as possible to facilitate needle insertion. Before puncture, the target lesion should be carefully inspected and located at the 5- to 7-o’clock position on the real-time EUS image. Color Doppler should be applied to avoid puncturing intervening vessels. Excessive movements of the tip of echoendoscope or the elevator should be avoided, as they increase the resistance to movements of the needle.
Although applying suction seems to lead to a better diagnostic yield rate than non-suction, the value of suction may vary depending on the target site and disease.9,11 There seem to be little difference in diagnostic adequacy between suction and capillary sampling with the stylet slow-pull technique.11,42 The accumulation of blood and blood contamination can reduce the specimen quality and result in blood clogging inside the needle lumen.11,43,44 A recent prospective study investigated the optimal number of needle actuations to obtain adequate cellularity with minimizing blood contamination. Significant blood contamination was observed with 20 actuations compared with 15 actuations when suction was applied, whereas 10 actuations showed a lower diagnostic yield than 15 or 20 actuations when suction was not applied.11 Therefore, 15 actuations were recommended for EUS-FNA of solid pancreatic masses.
The use of a stylet with EUS-FNA did not increase the diagnostic yield, whereas stylet use was associated with poorer sample quality in a previous prospective study.45 Expressing aspirate from the needle by air flushing seems to be preferred over reinserting the stylet because bloodiness was lower with air flushing than with stylet reinsertion. Moreover, expressing the aspirate by air flushing is easier and safer.9
Needle priming with saline or heparin was introduced to reduce blood clogging.43,46 These techniques provide better cellularity and specimen adequacy without negative effects on histologic interpretation and immunohistochemical staining.
The needle speed of actuations during EUS-FNA may be related to the diagnostic yield. Faster movement of the needle may increase tissue fracture and cause more cell detachment.47 Mukai et al48 introduced the “door-knocking technique,” named for the sound made by the needle handle hitting the stopper during a quick and forceful forward push. Although this technique did not improve the accuracy of the histologic diagnosis, a larger amount of tissue acquisition was possible. When the actual needle speed was measured during EUS-FNA, the diagnostic accuracy and specimen quality were higher when the acceleration was greater than 9.8 m/s2.49 The fanning technique, which is defined as using the needle to sample multiple areas within a lesion using the up/down knob of the echoendoscope, has been introduced, and showed superiority because fewer passes were required to confirm the pathologic diagnosis.50 The torque technique, which is defined as applying torque by twisting the shaft of the echoendoscope in the clockwise or counterclockwise direction without using the left/right control knob during EUS-FNAB, was evaluated in a prospective study of 124 patients with solid pancreatic masses, and the authors concluded that the torque technique enabled better histologic core procurement.41
The minimum number of needle passes to obtain adequate tissue is critical. The more needle passes are performed, the higher the diagnostic yield could be; however, performing numerous needle passes requires a long time and the probability of procedure-related adverse events might increase. In addition, if the number of passes is increased beyond a certain threshold, the diagnostic yield may not further increase, and time can be wasted unnecessarily. In the absence of ROSE, at least 5 to 7 passes were suggested for EUS-FNA of pancreatic malignancies.51,52 However, in a recent prospective study of 239 patients with solid pancreatic masses, performing more than four passes of EUS-FNA did not increase the sensitivity of detection.39 With the development of biopsy needles, as MOSE is widely implemented, the number of needle passes could be further reduced.
Because 80% to 100% of false-negative cases in EUS-FNA are correctly classified by contrast-enhanced harmonic EUS (CEH-EUS), CEH-EUS plays a complementary role in the diagnosis of solid pancreatic masses.53 In addition, CEH-EUS has been proposed as a method to improve lesion targeting because the contrast agent may enable better recognition of the puncture site by helping to avoid the necrotic area.53,54 EUS-FNAB under CEH-EUS may improve the diagnostic accuracy and adequacy with fewer needle passes.55–58
The presence of a cytopathologist to perform ROSE during EUS-FNA can improve the diagnostic performance by reducing inadequate samples and the need for additional passes.14,59–61 However, ROSE requires medical resources, including an on-site cytopathologist, as well as additional time and costs. A recent study reported the efficacy of MOSE for ensuring core tissue acquisition with a minimal number of needle passes and a high diagnostic yield.62 A macroscopic visible core larger than 4 mm is an indicator of an adequate sample that improves diagnostic accuracy.63 A recent international, multicenter, prospective, randomized clinical trial revealed that EUS-FNAB with MOSE required fewer needle passes to achieve an adequate diagnostic yield similar to that of the conventional method.64 MOSE should be implemented in real-world practice in terms of obviating the need for an on-site cytopathologist and saving additional costs and time for slide staining and interpretation.7
EUS-guided tissue acquisition is minimally invasive and safe, with an adverse event rate ranging from 0% to 3%.65 Adverse events include abdominal pain, acute pancreatitis, perforation, infection, bleeding, and tumor seeding. Most unpredictable adverse events are mild in severity and self-limiting.65 Although there is a concern that biopsy needles may cause more bleeding, it has been reported that there was no difference in the risk of adverse events, including bleeding, because biopsy needles could reduce the number of needle passes. A recent meta-analysis showed no difference in the incidence of adverse events between aspiration needles and the biopsy needles (1.8% vs. 2.3%, respectively; pooled risk ratio, 1.13; 95% confidence interval, 0.40–3.22;
There is no absolute contraindication to EUS-guided tissue acquisition, but caution is required in cases of cardiopulmonary instability, bleeding tendency with coagulopathy or thrombocytopenia, and recent use of anticoagulants or antiplatelets.67
It is important to obtain an adequate tissue sample, but it is also very important to process the obtained tissue appropriately to make a pathological interpretation. In addition to the pathological analysis, the detection of molecular alterations may be helpful for improving diagnostic accuracy.
A conventional smear with Papanicolaou or Diff-Quick stain is the usual method for the cytologic preparation of EUS-FNA specimens. However, conventional smears have problems such as bloody smears, dry artifacts, crushing artifacts, and thick tissue fragments, which obscure cytologic features and lead to a suboptimal diagnosis.12,55 Therefore, liquid-based cytology was introduced to solve the problems of conventional smears.68 In liquid-based cytology with EUS-FNA specimens, the ThinPrep method and SurePath system have mainly been studied.12 Prior studies comparing the ThinPrep method with conventional smears found that conventional smears were superior to ThinPrep in diagnosing pancreatic malignancies.69–71 However, the SurePath system showed similar diagnostic performance to conventional smears and reduced the blood background, thereby facilitating cell observation and justifying the use of liquid-based cytology for EUS-FNA over conventional smears when available.12
Molecular diagnostic techniques can enhance the diagnostic yield through various types of immunohistochemical staining and molecular analyses.72–74 EUS-guided tissue acquisition can provide cancer DNA for sequencing analysis. Although target sequencing is feasible even with cytology specimens, it can be difficult to proceed with whole-genome or whole-exome sequencing if the obtained samples are too small.75 EUS-guided tissue acquisition using a large-bore needle is more likely to achieve successful next-generation sequencing.76 A recent randomized crossover clinical trial reported that the specimen adequacy for genetic profiling was significantly better with biopsy needles than with aspiration needles.77
Additional genetic profiling using EUS-guided obtained samples, including
It will be crucial to obtain a larger amount of high-quality tissue in line with current medical trends, which are progressing toward precision medicine and targeted therapy. Table 2 summarizes the EUS-guided tissue acquisition and processing methods that can produce the highest diagnostic performance based on the results of previous clinical studies and meta-analyses.
Table 2 . A Summary of Optimal EUS-Guided Tissue Acquisition and Processing Methods.
|Needle shape||Franseen, fork-tip, and Menghini-tip needles are all recommended.|
Through-the-needle microforceps are promising for pancreatic cysts.
|Needle gauge||A 22-gauge needle is recommended considering its convenience and clinical evidence.|
The 19-gauge needle seems to be in the spotlight again because more tissue is better for genetic profiling.
|Tissue acquisition technique||Rapid insertion and slow withdrawal of needle under negative suction, 15 times.|
The fanning technique or torque technique.
|Confirmation of adequacy of the obtained sample||Macroscopic on-site evaluation to confirm histologic core.|
|Cytology preparation||Liquid-based cytology (SurePath).|
|Ancillary test||Addition of molecular profiling.|
EUS, endoscopic ultrasound..
This work was supported by National Research Foundation (NRF-2019R1C1C1006851).
No potential conflict of interest relevant to this article was reported.
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