How to perform endoscopic ultrasonography-guided fine-needle aspiration and fine-needle biopsy

Key points

Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) with cutting-type needles has replaced EUS-fine-needle aspiration (FNA) as the current gold standard for optimal tissue acquisition.
EUS-FNA with or without cell block remains an excellent alternative when access to FNB is limited or deemed unnecessary.
22-g needles provide better histological yield when performing FNB on solid masses, but 25-g needles should be used for FNA.
19-g FNA and FNB needles provide more adequate samples for liver biopsy compared with 22-g needles.
Use of the stylet does not increase the yield of EUS-FNA/B and therefore unnecessarily increases procedural complexity.
Sampling the lesion in many regions is an important predictor of success in EUS-FNA/B.
The needle should be kept in the visual plane at all times.
Excessive force should never be used to pass the needle sheath past an acute bend in the endoscope tip.
Cyst aspiration should be performed only if there is evidence that cyst fluid analysis will influence management. In such cases, a single puncture should be performed and all fluid should be aspirated if at all possible. Attempts at cyst wall puncture should be avoided, and peri-procedural antibiotics are recommended.

A brief history of EUS-guided needle sampling

Endoscopic ultrasound (EUS)-guided needle sampling was first introduced in 1992. Over the past decades, this technique has provided some of the most clinically powerful information that EUS has to offer—particularly for the confirmation of the presence (or absence) of malignancy and/or metastasis to secondary sites.

First-generation needle devices use a single-bevel hollow needle (similar to venous puncture needles) and are available in several sizes (19, 22, 25 g) ( Fig. 19.1 ). These needles work mainly as “scraping” needles, shearing cells from the lesion of interest, which are subsequently expelled on a microscope slide and/or cytology medium in order to provide a cytological diagnosis. These fine-needle aspiration (FNA) needles provide adequate sample cellularity in most epithelial cancers, with a sensitivity for malignancy of over 90% in experienced hands. If needed, a cell block call also be obtained, to perform immunohistochemistry necessary to differentiate certain lesions such as GISTs, neuro-endocrine tumors, or identify the primary site of an adenocarcinoma. As an adjunct to EUS-FNA, the presence of rapid on-site evaluation (ROSE) of cytological slides helps increase specimen adequacy and minimize the number of passes. Several studies have compared the efficacy of 22-g versus 25-g FNA needles. Three meta-analysis have shown that 25-g needles have increased sensitivity over 22-g needles, ^, ^, although two of the studies did not show statistical significance. The inherently more flexible and smaller diameter 25-g needle appears preferable, since it is easier to manipulate and appears to facilitate puncture of harder lesions.

• Fig. 19.1, Currently available needles for EUS-FNA and EUS-FNB.

Despite the efficacy of cytology needles, it is clear that cytology and cell block cannot provide as much information as histology (e.g., lymphoma subtype, neuro-endocrine tumor G grade, gene sequencing, detection of microsatellite instability, diagnosis of autoimmune pancreatitis, diagnosis of liver disease, etc.). Many needle devices and techniques were developed over time in order to obtain histological specimens with EUS-guided fine-needle biopsy (EUS-FNB), often resulting in more cumbersome techniques with disappointing results. The first dedicated EUS-guided FNB device was the Quick-Core needle (Cook Medical, Bloomington, Indiana), a 19-g Tru-Cut device similar to percutaneous liver biopsy needles, comprising a needle tip, cutting sheath, and specimen tray. Unfortunately, it was cumbersome, often misfired if the scope was not straight, and was unable to obtain histological cores consistently. High negative pressure suction with 22-g or 19-g FNA needles also produced poor results. ^, In 2012, a reverse-bevel needle (ProCore needle, Cook Medical, Bloomington, Indiana) became commercially available. Although this needle required less passes in order to achieve adequate cytological cellularity, histological specimens were obtained only 78% of the time, comparable to standard EUS-FNA needles.

Recently, a new generation of EUS needles was introduced ( Fig. 19.1 ). One of those needles is a modified version of the ProCore needle, with two forward bevels spaced out at different levels with a unique 20-g diameter size. Shortly after, newer needles featuring novel multiple sharp and spiked prongs emerged: (1) a forked-tip needle (SharkCore needle, Medtronic Corporation, Newton, Massachusetts) and (2) a modified Franseen-tip needle (Acquire needle, Boston Scientific, Natick, Massachusetts). These two needle types allow them to “cut” very effectively into tissue and to produce histological cores with a success rate over 90%, using a standard FNA technique.

Several studies compared newer generation needles among themselves. A randomized cross-over trial by Karsenti comparing the 22-g Franseen needle with the 20-g forward-bevel needle in 60 patients with pancreatic masses revealed that the Franseen needle provided better diagnostic adequacy (100% vs 87%, P = .001) and diagnostic accuracy (87% vs 67%, P = 0.02) over the forward-bevel needle. Another randomized prospective trial by Kurita comparing these same needles for the diagnosis of auto-immune pancreatitis in 100 patients showed adequate histological sampling up to 78% in the Franseen group compared to 45% in the forward-bevel group ( P = .001).

A recent meta-analysis by Facciorusso covering 24 studies with 6641 patients reported a histological procurement of 92.5%, with no difference between Fork-Tip or Franseen needles, and with significantly less needle passes compared with FNA.

Although FNB needles are slightly more costly than FNA needles, a recent study by Chen showed that EUS-FNB alone was noninferior to EUS-FNA with ROSE, was associated with fewer needles passes (2.3 vs 3), required less procedure time (19.3 vs 22.7 minutes), with comparable cost. Another recent study by Lin showed that EUS-FNB shortened the learning curve of EUS-guided tissue acquisition in trainees, with diagnostic sensitivity over 80% after 10 FNB procedures and a significant decrease of needle passes after 20 procedures. No significant changes were noted after 30 FNA procedures.

In conclusion, the current data support a shift to the use of cutting-type EUS-FNB needles instead of all other available needle types, whenever possible.

Choosing the correct needle

Cutting-type FNB needles should be considered as a first choice for EUS-guided tissue sampling. They are available in 25-, 22-, and 19-g sizes. The 25-g needle is easy to manipulate and provides excellent samples for cytology, but provides adequate histological cores in less than 90% of cases. Nineteen-gauge needles provide excellent cores, but they are more costly, their stiffness makes them difficult to manipulate when the scope is bent, and they do not provide increase in diagnostic accuracy for malignancy compared with 22-g needles. The 22-g size combines excellent flexibility with excellent diagnostic accuracy, which would suggest it is the optimal choice for EUS-FNB, for most indications. ^,

However, the 19-g needle appears to be preferable for parenchymal liver biopsy. Twenty-two-gauge needles do not provide sufficient portal tracts for adequate pathological reading and result in higher fragmentation. In comparison, percutaneous liver biopsies are performed with a 16-g or 18-g needle. Thus a 19-g needle should be used for parenchymal liver evaluation, as studies have consistently shown that 19-g needles were superior to 22 g in that regard. As for needle type, a recent prospective randomized trial by Ching-Companioni comparing 19-g FNB needles with 19-g FNA needles in 40 patients has shown that 19-g FNB needles yielded longer specimen lengths (1.78 cm vs 1.05 cm, P < .001) and more complete portal triads (42.6 vs 18.1, P < .001) compared with 19-g FNA needles.

Nineteen-gauge FNA needles are preferable for cyst aspiration. The larger caliber allows quicker and more effective complete aspiration, especially with viscous mucinous fluid. However, since the 19-g needle may be more difficult to manipulate, the 22-g FNA needles may be considered when aspirating smaller cysts.

Current data support the use of the 25-g FNA needle for cytology, when histology is considered unnecessary (e.g., confirmation of recurrent cancer or distant metastases). It may also be preferable in cases with an increased risk of bleeding (e.g., patients in whom anticoagulation or antiplatelet therapy that cannot be discontinued safely). ROSE may also be helpful in such cases, to minimize the number of passes required. Table 19.1 summarizes which needle types should be preferred when attempting EUS-guided sampling.

TABLE 19.1

Recommended Needle Type for EUS-Guided Sampling

22-g FNB needle
- Consider for sampling of all solid masses

25-g FNA needle
- Consider if 22-g FNB too challenging
- Challenging anatomy (e.g., 2nd duodenum)
- Challenging lesion (e.g., small, mobile, indurated mass)
- Challenging patient (e.g., anticoagulation, antiplatelet use ^a )
- May be used if primary histological diagnosis already known (e.g., lymph node sampling in luminal cancers)

19-g FNB needle
- Parenchymal liver histology

19-g FNA needle
- Cyst fluid analysis (may consider 22-g FNA for smaller cysts)

a Aspirin or nonsteroidal antiinflammatory drug use is not contraindicated for FNB.

How to perform EUS-FNA and FNB?

Like any procedure, proficiency requires adequate experience, but EUS-guided sampling is not a universally difficult technique to master. Some cases are more technically demanding than others. Sampling a 5-mm pancreatic nodule buried deep in the uncinate process is certainly more challenging than sampling a 4-cm subcarinal lymph node. Interestingly, some of the easiest cases provide information that can have a tremendous impact on patient management (e.g., such as prevention of surgery by documentation of mediastinal node involvement in a patient with lung cancer). EUS-guided sampling can be broken down into a series of steps. Proper execution of each step will make the procedure easier and increase the yield for malignancy. This section will provide a detailed description of a generic EUS-guided sampling technique that can be applied to the great majority of lesions and to both FNA and FNB needles. Special consideration will also be given to issues that provide particular challenges.

Indications and contraindications

Indications for EUS-guided tissue acquisition are broad. Tissue sampling is performed most often to confirm suspected cancer, although cores produced by FNB may also be useful in benign conditions such as diagnosing auto-immune pancreatitis, hepatocellular disease, sarcoidosis, or infections (e.g., tuberculosis, fungal disease). Table 19.2 summarizes the common sites for performing EUS-guided sampling.

TABLE 19.2

Common Sites for Performing Endoscopic Ultrasonography-Fine-Needle Sampling

Pancreas
Bile duct
Digestive wall lesions ^a
- Suspicious wall thickening
- Subepithelial lesions
Adrenal glands
Liver
Retroperitoneal masses
Lymph nodes
Posterior mediastinum
- Suspicious lymph nodes
- Pulmonary masses ^b

a Digestive wall lesions include the esophagus, stomach, duodenum, and rectum.

b Pulmonary masses must abut the posterior mediastinum to be visualized under endoscopic ultrasonography.

Contraindications to EUS-guided sampling are limited. Before performing the procedure, the endosonographer must be certain that there is a reasonable chance that tissue sampling will be clinically useful. As a general rule, FNA or FNB should be avoided in patients with significant coagulopathy (international normalized ratio [INR] >1.5, platelets <100,000, recent use of antiplatelet therapy [such as clopidogrel, prasugrel, or ticagrelor] or anticoagulants). It is currently unclear whether FNB needles increase the risk of bleeding more than FNA needles.

Patients receiving antiplatelet therapy should withhold them for 7–10 days prior to the procedure if they carry a low thrombotic risk. However, the use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) can be continued before undergoing the procedure and should not be stopped. Patients receiving anticoagulant therapy such as warfarin or novel oral anticoagulants (NOACs) should discontinue their medication prior to the procedure (3–5 days for warfarin, 48–72 hours for NOACs). If the patient is at high risk for thromboembolic events, bridge therapy with low-molecular-weight heparin should be considered.

Some high-risk patients may not safely discontinue their treatment. In a situation where the risk of stopping the therapy is potentially greater than the risk of EUS-induced bleeding, it may be reasonable to attempt EUS-FNA with a small-gauge (25 g) needle instead of EUS-FNB and minimize the number of passes (with the presence of ROSE).

Finally, certain anatomical challenges may also contraindicate EUS-guided sampling, such as a large vessel or duct interposing itself between the targeted lesion and the ultrasound probe. Lymph nodes may not be accessible if the primary mass is preventing direct node sampling, carrying the risk of false-positive results. Table 19.3 provides an overview to EUS-guided sampling contraindications.

TABLE 19.3

Contraindications for Performing Endoscopic Ultrasonography-Fine-Needle Sampling

Contraindication for endoscopic examination
- Cardiac or respiratory instability
- Suspected perforated viscus
- Nonfasting patient or undecompressed upper gastrointestinal obstruction
Coagulation disorder
- Anticoagulants
- Antiplatelet therapy ^a
Inaccessible lesion
- Lesion not visualized
- Large vessel or duct interposition
- Metastatic lesion with primary mass interposition
EUS FNA/B results will not alter subsequent management

a Aspirin or nonsteroidal antiinflammatory drug use is not contraindicated.

Steps for EUS-guided FNA or FNB

1.
Verify the indication.
2.
Localize the lesion and position the echoendoscope.
3.
Insert the EUS needle into the echoendoscope.
4.
Position the lesion in the needle path.
5.
Puncture the lesion and move the needle within the lesion.
6.
Withdraw the needle and evaluate the sample.
7.
Prepare the needle for subsequent passes.
8.
Evolving trends in EUS FNA/B:
- a.
  Use of the stylet
- b.
  Use of suction
9.
Needle-sampling particularities according to site:
- a.
  Esophagus
- b.
  Stomach
- c.
  Duodenal bulb
- d.
  Duodenal sweep (D2)
10.
EUS-FNA of cystic lesions

Verify the indication

Before performing EUS-guided tissue sampling, the indication should be clear and the endoscopy suite and team adequately prepared. Like any test, it does not need to “change management” to be useful. However, before considering EUS-guided tissue sampling in a given patient, it should be clear that the information obtained has a reasonable chance of being clinically useful (to those managing the patient and/or to the patient). If the endosonographer is not in charge of the patient’s management, his or her opinion as to the value of the information need not affect the decision to perform the procedure unless there is compelling evidence that the risks of the procedure will likely far outweigh the possible benefits. If there is any doubt, these issues should be addressed with the referring physician before the procedure (or even during the procedure) if necessary.

EUS-guided tissue sampling should be avoided if it will clearly not influence management or treatment, if there is an excessive risk of puncture-related complications (e.g., bleeding, infection, trauma to surrounding structures), or if there is a risk of tumor seeding that could worsen clinical outcomes. Although very rare, tumor seeding has been described with EUS-guided sampling in over 30 cases. ^, In the presence of a potentially resectable cancer, EUS-guided tissue sampling should be reconsidered if the biopsy tract will not be included in the surgical specimen (e.g., sampling through the gastric wall in the case of a pancreatic body lesion). Instead, if at all possible, an attempt should be made to perform biopsies through a part of the gut wall that will be removed should the patient go to surgery (e.g., lesions of the pancreatic head/genu should be biopsied through the duodenum if possible). Interestingly, virtually all reports regarding pancreatic tumor seeding with EUS-guided sampling involve the gastric wall (in body-tail masses), lending credibility to the fact that surgically resected sampling tracts (such as the duodenal wall resected during a Whipple’s procedure) pose a much lesser risk. ^,

To avoid seeding extraluminal sites such as nodes, EUS-guided sampling should never be performed through an area of the gut wall that is overtly or possibly infiltrated by malignancy. Such sampling can contaminate the intended target with neoplastic cells from the primary tumor, erroneously overstaging the nodal status of a tumor.

When faced with the possibility of performing sampling on multiple sites, one should focus on the lesion likely to provide the most relevant information and/or highest cancer stage first. For instance, in the setting of a pancreatic head mass with suspicious liver nodules, sampling of the liver lesions may provide a positive histological diagnosis and confirm that the patient is not a surgical candidate. When sampling various sites, the endosonographer should begin by targeting the most distant metastatic site before moving on to the primary lesion in order to avoid seeding neoplastic cells in more remote locations (for instance, one should not sample a neoplastic pancreatic mass and then use the same needle to sample a moderately suspicious liver nodule).

Localize the lesion and position the echoendoscope

Whenever possible, the echoendoscope should be straight. This makes needle movement easier and reduces the risks of damage to the accessory channel during insertion of the needle into the scope.

In our experience, most pancreatic lesions (including pancreatic head/uncinate lesions) can also be sampled with the scope in a straight position. To do so, the scope should be passed into the second duodenum and then withdrawn into a “short” position. This short-scope position also allows better introduction of the needle into the scope, including larger 19-g needles. However, when withdrawn too far, this position will become unstable and the scope will slip into the stomach. Lesions near the pancreatic genu are often difficult to biopsy with this withdrawal technique, because they often become visible just at the moment that the position becomes unstable.

For these lesions (and any other lesions that cannot be accessed with the scope in a straight position), it is necessary to assume a “long” position, with the scope in the bulb or prepyloric region. This position will also provide a mechanical advantage when trying to puncture indurated lesions in the pancreatic head region.

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