The patient underwent a diagnostic EUS with a linear array echoendoscope. Many malignant-appearing, round, hypoechoic lymph nodes with well-defined margins were visualized in the aortopulmonary window, the paraesophageal mediastinum , and the mediastinal periaortic region. The largest measured 10 by 10 mm in maximal cross-sectional diameter (Fig. 23.1). A round, well-defined, hypoechoic and homogenous, 20 mm by 20 mm in maximal cross-sectional diameter mass was identified in the pancreatic body (Fig. 23.2). The mass appeared atypical for pancreatic adenocarcinoma . There was no sign of significant endosonographic abnormality in the left lobe of the liver.

This patient had a pancreatic mass and diffuse lymphadenopathy. The EUS findings were not typical for a pancreatic adenocarcinoma . However, a pancreatic cancer with diffuse metastasis still remained in the differential diagnosis. The atypical imaging findings of diffuse lymphadenopathy also raised suspicion of pancreatic lymphoma. As management of these two conditions differ, a definite cytological or histological diagnosis was necessary to guide treatment of the patient at this stage, and EUS-FNA of both the lymph nodes and pancreatic mass was required. The first EUS-FNA should always target the lesion, which likely represents the most advanced stage of malignancy . This approach will help prevent subsequent seeding.

When sampling a suspected pancreatic cancer is indicated, EUS-FNA should be the first-line procedure. It has significant advantages over percutaneous US or CT-guided biopsies [11, 12]. EUS and EUS-FNA are superior for detecting early malignancies, obtaining cytologic material, and minimizing the risk of tissue seeding. EUS-FNA may diagnose a potentially resectable mass or pancreatic metastasis, and exclude other pancreatic tumors such as lymphoma or neuroendocrine tumor, in addition to benign disease such as chronic or autoimmune pancreatitis.

A preoperative diagnostic EUS-FNA is controversial in patients who are good surgical candidates with a adenocarcinoma . The negative predictive value of EUS-FNA for pancreatic cancer is approximately 70 %; thus, a negative result cannot rule out malignancy with adequate reliability [13–15]. Therefore, routine preoperative EUS-FNA of potentially resectable pancreatic adenocarcinomas is not generally advised. However, in cases where other types of pancreatic malignancies (e.g., neuroendocrine tumors, lymphomas, metastatic disease) are suspected, EUS-FNA is indicated to assist in planning appropriate management.

Initial planning and preparation for EUS-FNA is similar to other endoscopic interventions. Prior to starting the procedure, the medical history and records of the patient should be reviewed with all necessary laboratory and radiological tests, and then informed consent should be obtained after discussing the indication, benefits, and risks of the procedure with the patient and the family. The diagnostic success of EUS-FNA is highly related to the preparation of the patient and instruments as well as the expertise of the whole endoscopy team. Therefore, each step of the procedure needs to be carefully planned and executed with the entire team. The risk of bacteremia is rare and similar to other endoscopic procedures. As such, prophylactic antibiotics are not routinely recommended [16]. Serious infectious complications have only been reported after EUS-FNA of cysts (e.g., pancreatic and mediastinal) and the American Society for Gastrointestinal Endoscopy (ASGE) guideline recommends periprocedural antibiotics only in these patients [17, 18].

EUS alone, without FNA, is a low-risk procedure for bleeding, but EUS with FNA is classified as a high-risk procedure. There is no need to stop aspirin, thienopyridines including clopidogrel or warfarin for patients undergoing a low-risk procedure for bleeding [19]. Aspirin may be continued even in patients undergoing EUS-FNA of solid lesions, but clopidogrel should be discontinued 7–10 days prior to the procedure. Warfarin should be stopped 2–5 days before the procedure in all patients who are scheduled for EUS-FNA and restarted within 24 h after the procedure. A bridge therapy with low molecular weight heparin should be considered in patients with higher risk conditions for thromboembolic event [19]. These decisions regarding antiplatelet agents and anticoagulants should be discussed with the patient’s cardiologist and/or neurologist prescribing those medications.

Sudden movements during FNA may lead to injury of adjacent structures and effective sedation of patients is important for a complication-free procedure. Sedation may be provided with intravenous conscious sedation (IVCS) or with monitored total anesthesia during EUS-FNA. A recent study compared the impact of IVCS and general anesthesia (GA) on diagnostic yield of EUS-FNA in patients with pancreatic mass [20]. Anesthesiologist-delivered GA was associated with a significantly higher diagnostic yield of EUS-FNA compared to IVCS. The authors commented that GA may improve EUS-FNA yield by improving patient cooperation and stillness during the procedure. There was no difference in the complication rates between the groups.

Before proceeding with EUS-FNA, a complete diagnostic EUS should be performed to evaluate the lesion and adjacent structures to allow adequate staging and in order to choose the optimal needle tract. A radial EUS examination is usually suggested for areas other than the pancreas, but selecting the radial or linear scope for diagnostic EUS depends on the endoscopist’s experience. The linear echoendoscope provides complete visualization of the pancreas. After the target lesion is identified, the scope should be placed in a stable position adjacent to the lesion, and if possible, within the projected plane of the needle path. Doppler function should be utilized to exclude an interposed vessel between the transducer and the target lesion.

Once the target lesion is localized and an appropriate position is achieved, the needle catheter device is advanced through the biopsy channel to begin the puncture. The location of the target lesion affects the difficulty of the procedure. In general, transduodenal FNA is difficult, while transgastric is easier and transesophageal easiest.

EUS-FNA is classically performed with 19-, 22-, and 25-gauge (G) aspiration needles from several manufacturers (Table 23.2 and Fig. 23.3). There is no optimal needle size for EUS-FNA , and each size may have advantages and disadvantages depending on the location and type of lesion. Larger diameter needles do not increase the risk of the procedure, and no significant difference in complication rates has been shown among the different sized FNA needles [6]. The 19G needle is the stiffest and may be difficult to manipulate in the duodenum where the scope is sharply angulated. For this reason, technical failure rate is higher with 19G needles used for pancreatic head lesions [21, 22]. Although the 19G needle may obtain tissue fragments from suspected tumors and potentially increase diagnostic accuracy, it may cause more trauma and bloodier samples. Conversely, a 25G needle offers ease of use and less risk of a bloody aspirate [23]. The 25G needle may be particularly useful for difficult pancreatic head lesions [24]. Several prospective studies have compared the 22G and 25G needles for their performance, diagnostic accuracy, and safety [7, 25, 26]. In general, diagnostic yield and complications appear comparable between the 22G and 25G needles [27, 28]. Endoscopists should be familiar with all needle sizes and choose the size based on the flexibility needed, the size which may provide optimal tissue yield, and the safest size for a particular location and type of lesion.

A new 19G aspiration needle made of nitinol with enhanced flexibility (Expect flex, Boston Scientific, Marlborough, MA, Fig. 23.4) was designed to overcome the limitations of current 19G needles. A recent study demonstrated successful tissue acquisition adequate for cytological assessment in all 38 patients (100 %), which included transduodenal passes, and therapeutic interventions were also effective in 12 patients [29]. In another pilot study with this needle, EUS-FNA was successful in all eight cases with six involving the pancreatic head, and adequate specimen was obtained with a mean of 1.2 passes [30].

To obtain adequate histologic samples and overcome some limitations of EUS-FNA , EUS-fine needle biopsy (EUS-FNB) has been performed with a 19G Tru-cut biopsy needle (TBN) (Fig. 23.5). The needle consists of a 5 mm stylet tip, an 18-mm specimen tray, a 19G internal cutting sheath, the outer catheter sheath, and the handle portion. It permits procurement of tissue specimen automatically with a spring-loaded handle mechanism. The needle is advanced to the target lesion with the handle in the retracted firing position. The specimen tray is inserted into the target lesion and the handle is pressed forward until resistance is felt. The specimen tray and cutting sheath are visualized within the target tissue with distinct echo features. Increased pressure on the handle fires the device, moving the cutting sheath quickly over the tray to acquire a tissue sample. Straightening the echoendoscope and needle, proper device orientation, and targeting the lesion are important technical details when using this needle. By preserving the tissue architecture, this needle may be more helpful for the diagnosis of specific conditions such as gastrointestinal stromal tumors , lymphomas, well-differentiated neoplasia, neuroendocrine tumors, and autoimmune pancreatitis . However, the rigidity of the needle limits its usage especially in difficult locations such as duodenal bulb, fundus, and antrum [22].

Recently, 19G, 22G, and 25G biopsy needles were designed with a cutting knife (Procore, Cook Medical, Fig. 23.6, Table 23.2). The flexibility of the 22G and 25G core needles may offer advantages in difficult locations. Several recent studies compared the diagnostic yield of 22G aspiration needles with 22G core needles for solid lesions of the pancreas and gastrointestinal tract with inconclusive findings. Depending on the study, the diagnostic yield of the 22G aspiration needle was equal, superior, or inferior to the 22G core biopsy needle [6, 7, 28]. Procore needles may require fewer passes compared to aspiration needles. The diagnostic yield on the first pass of the 22G Procore needle was approximately twice compared to the 22G aspiration needle [31]. Downsides of the core needles include their greater expense and need for additional training and technical assistance. A new core needle (SharkCore fine needle biopsy, Covidien) is now available in 19G, 22G, and 25G with a unique design of 6 cutting surfaces, and needs study to determine its utility and place within the current armamentarium of aspiration and biopsy needles. Both types of needles may offer advantages and may prove more useful in different lesions and individuals. Table 23.3 summarizes suggested needle type and size according to specific characteristics of the case.

In our case, the mediastinal and peripancreatic lymph nodes were suitable for EUS-FNA . For better staging and to prevent subsequent seeding, the first EUS-FNA should target the lesion, which likely represents the most advanced stage of malignancy . Thus, the mediastinal lymph nodes were targeted first by a transesophageal approach. For lymph node aspiration, 22G and 25G needles may be easiest to use. The mass in the pancreatic body was accessed transgastrically. For atypical lesions , a larger needle to obtain tissue fragments for histology may be more helpful for diagnosis . Considering all these factors, starting with a 22G for the lymph nodes and then a 19G for the pancreatic mass or using a 22G aspiration needle for both lesions are reasonable choices in this case. EUS-FNB with a 22G Procore needle for both the lymph nodes and pancreatic mass may be an alternative, especially for atypical lesions, and if Rapid Onsite Evaluation (ROSE) is not available.

Most single-use EUS-FNA needles are very similar in design and operation [32]. They consist of a hollow metallic needle inside a semirigid protective sheath with a plastic rigid cylinder handle containing a port (Figs. 23.3, 23.4, 23.6). From the port, there is a solid removable stylet inside the needle to enhance its rigidity during puncture and to prevent clogging the needle tip with intestinal mucosa. The port is also used to attach a vacuum syringe. The handle is attached to the accessory channel of the echoendoscope via a Luer Lock to stabilize the system during use. Markings at 1 cm intervals on the handle enable to set and monitor the depth of the needle. The maximum needle length from the tip of the echoendoscope is usually 8–9 cm. The handle has a stopping device to set the maximum needle excursion. This safety mechanism helps to keep the needle within the limits of the target lesion. To facilitate the passage of multiple needles through a single delivery catheter, a new system called BNX (Beacon Needle Exchange) has been developed (Beacon Endoscopic, Covidien) (Fig. 23.7). The system has the ability to remove the needle from the sheath and place different sized needles through the same sheath to perform multiple passes. The aim of the system is to increase the diagnostic yield of EUS-FNA with low cost and increased efficiency, but no clinical study has been published yet about the effectiveness of this system.

After the target lesion is identified and the scope placed into a stable and proper position for the lesion, the needle system is inserted through the working channel of the echoendoscope and advanced to the tip of the scope with the lesion in close proximity. To achieve the proper position, the transducer of echoendoscope should contact the luminal wall firmly near the target lesion, and the lesion should be within the potential direction of the needle in order to perform FNA without difficulty, which is usually at the 6 o’clock position on the EUS screen. Slow movements of the echoendoscope and using the up and down knob and the elevator may help to achieve the proper position and to set the needle angle. Straightening the tip of the echoendoscope is especially important when puncturing lesions located in the pancreatic head. It may be difficult to pass the needle system if the echoendoscope is angulated. In this situation, instead of pushing the system by force, the endoscopist should reduce the scope to a straight position, insert the needle system completely, and then reposition the scope at the target lesion. The use of small gauge needles reduces the difficulty of passing the needle through an angulated scope.

After the needle system is completely inserted into the channel, it is firmly screwed onto the biopsy channel and the needle stop is set to limit the maximum distance that the needle can be advanced. The stylet inside the needle may prevent contamination of the needle tip during puncturing the intestinal wall; although, recent studies have questioned the benefit of using a stylet [33, 34]. If the stylet is used, it is withdrawn slightly before advancing the needle into the target tissue to facilitate entry and then may be readvanced to remove any potential tissue clogging the tip of the needle. Transgastric puncture sometimes may be difficult due to the thicker and redundant gastric wall. Suctioning the gastric wall and advancing the needle with a brisk but controlled, forceful maneuver may overcome this problem.

The needle is always advanced into the target lesion under direct EUS guidance. To avoid excessive needle excursion, the palm of the right hand grasps the handle with the last three fingers and the movable part is controlled by the thumb and index finger. The elevator of the scope can help deflect the needle with small adjustments. After the lesion is punctured properly, the stylet may be removed completely or left inside the needle. If a vacuum syringe is used, the stylet is removed completely after puncturing the lesion and a 10 ml vacuum syringe is affixed to the handle port for permanent suction. Then, the needle is moved back and forth about 5–10 times through the lesion to shear-off cells under sonographic control. If a vacuum suction syringe is not used, the stylet is retracted slightly inside the needle and the needle passed through the lesion. Before withdrawing the needle from the lesion, 5–10 ml of suction may be applied for a few seconds. The endoscopist should be careful to keep the needle inside the lesion and to turn the suction off before withdrawing the needle from the lesion. After the procedure has been completed, the needle is removed from the scope and the aspirant is expressed onto a slide or container. An air-filled 10 ml syringe or stylet through the needle can be used to express the aspirate from the needle tip. After all the material is evacuated from the needle, it is cleansed and rinsed in sterile saline or alcohol by aspiration and flushing. Then it is reassembled for the next pass.