Endoscopic Ultrasound-Guided Fine Needle Aspiration of the Pancreas

Richard A. Erickson, M.D., F.A.C.P., F.A.C.G.

 

Keywords

Pancreatic cancer, biopsy, endosonography, fine needle aspiration

Introduction

Few clinical problems warrant as much urgency for definitive diagnosis as pancreatic masses. Because of its unique diagnostic capabilities, endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration (EUS-FNA) have become important tools in the evaluation of pancreatic masses (1-7). The first commercially available radial echoendoscopes were introduced in Japan (8) and Europe (9) in the mid to late 1980s. Although radial instruments were used for fine needle aspiration (10), EUS-FNA did not become technologically practical until the early 1990s (11) when linear echoendoscopes were introduced. This introduction generated ultrasonic images parallel to the shaft of the instrument over the exit port of the biopsy channel. With this modification, objects exiting the biopsy channel of the endoscope (e.g., a needle) could be followed and guided into lesions in "real-time.” Very soon after the introduction of linear echoendoscopes, the first report of EUS-FNA of the pancreas appeared (12) and, shortly thereafter, of EUS-FNA of a pancreatic cancer (13). Since 1994, there have been numerous series reporting on the safety, technique, and yield of EUS-FNA of the pancreas (4, 6, 10, 14-24). This review will focus on our current understanding of the utility, technique, and safety of EUS-FNA of the pancreas.

Body

UTILITY OF EUS-FNA OF THE PANCREAS
The foremost indication for EUS-FNA of the pancreas is for the definitive diagnosis of pancreatic masses. Approximately 90% of pancreatic neoplasms are adenocarcinomas, another 5% are cystic lesions, and some 2-5% are neuroendocrine tumors (25). The remainder are metastatic lesions to the pancreas, primarily from renal cancer, lung cancer, and lymphomas. Because cystadenocarcinomas (26) and neuroendocrine tumors (27) of the pancreas have a significantly better prognoses than pancreatic adenocarcinoma, accurate cytologic preoperative identification can significantly alter the subsequent management of these patients (28).

As an imaging modality, many series (1, 3-6) have demonstrated that EUS is superior to CT, MRI, and ERCP (29) in the diagnosis of pancreatic diseases and especially neoplasms. Detection rates for pancreatic cancer using EUS, even lesions less than 3 cm, have been consistently in the range of 95-100%. However, the superiority of EUS for pancreatic pathology detection is being continually challenged by the technologic advances in CT and MRI imaging, although well-controlled, head-to-head trials of comparable patients are still scare (30). Positron emission tomography (PET) also may play a significant role in pancreatic cancer detection, especially in looking for occult pancreatic malignancies or metastatic disease (31). However, just finding an imaging abnormality is often not enough to determine subsequent management of patients with pancreatic masses. The rational for attempting to obtain a cytologic diagnosis of most pancreatic masses have been detailed elsewhere (1, 32). When combined with FNA capabilities, EUS has the powerful advantage over all other imaging techniques of being able to immediately sample any suspicious lesions seen in the pancreas. The one area where malignancies can be still easily missed by EUS, even with EUS-FNA, is in the setting of underlying chronic pancreatitis (3, 6, 12, 18, 23, 33-35). No single or combination of imaging modalities has yet proven accurate in definitively determining when a patient with chronic pancreatitis has developed pancreatic cancer. This clinical dilemma may have to await continued progress in the molecular diagnosis of cancer (36, 37).

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TECHNICAL CONSIDERATIONS
The technique of EUS-guided FNA has been described in detail elsewhere (19, 23) but basically involves passing an 18 to 22 gauge metal needle through the biopsy port of a linear echoendoscope under real-time guidance into an endosonographically visualized pancreatic mass, associated lymph node, liver metastasis, or fluid collection. The needle is then moved back and forth 5 to 10 times through the lesion with varying degrees of suction applied to it. The specimen is then deposited on a cytology slide(s) for immediate fixation and staining and cytopathologic examination. Since its initial inception, there have been significant technologic advances in needle technology and are now at least three manufacturers of effective disposable and semi-disposable EUS-FNA needles. There are also new innovative devices such as spring activated needles to help penetrate firm lesions and cutting needles to provide small cores of tissue to try and perhaps improve diagnostic accuracy (38).

Biopsy most distant disease first: Because the specificity of a cytologic diagnosis of malignancy is almost 100%, in performing EUS-FNA for pancreatic neoplasms, a general guiding principle is to try to cytologically confirm the most advanced stage of the tumor. Thus, during EUS-FNA of pancreatic masses, needle aspiration should first be done of any potentially metastatic disease in the liver (Figures 1-4) or in the peritoneum (ascites), then any distant pathologic lymph nodes, then regional nodes, and, finally, if these are negative, the primary mass can be aspirated. In addition to cytologically documenting the most advanced degree of the patient's tumor stage, EUS-FNA of malignant liver lesions is usually easier than pancreatic mass FNA in that it only takes 1 to 2 needle passes for a positive cytology. Likewise, lymph nodes usually only require 1 to 4 passes to obtain a cytologically positive diagnosis (17, 23, 39-41).

Cytopathology interaction: The yield of EUS-FNA of primary pancreatic malignancies has been reported to run from 80-93% (4, 6, 10, 14-21, 23). Obtaining a high yield of positive diagnoses in pancreatic EUS-FNA is very dependent on FNA technique and the active involvement of a cytopathologist. Most very active EUS-FNA centers have a cytopathologist on site to provide immediate feedback on the adequacy and preliminary cytologic diagnosis (10, 14, 15, 18-21, 23). Live feedback from a cytopathologist results in about a 10% increase in the yield of a positive diagnosis (17, 21, 23).

Where to aspirate a pancreatic mass: Choosing what part of a pancreatic mass to aspirate is something of an art that comes with experience in aspirating these lesions. The most difficult pancreatic masses to aspirate are those located near the uncinate portion of the pancreas where it can be very hard to direct the needle around the second and third portion of the duodenum to enter the lesion. Novice endosonographers are also surprised by how much force it may take to make an FNA needle penetrate deeply into the typical pancreatic adenocarcinoma because of the surrounding desmoplastic reaction. The usual temptation is to biopsy deep into the center of a mass; however, this may yield only necrotic debris with few intact tumor cells. EUS-FNA of the edge of the tumor may yield only peritumor pancreatitis (Figures 5A and 5B). The best yield of diagnostic cells usually seems to come from 1 cm to 2 cm deep to the echolucent margin of the tumor (Figures 5B-7). Color flow Doppler can be used prior to EUS-FNA to help avoid vessels overlying the proposed path of the aspiration needle such as are seen when there is underlying portal vein or splenic vein obstruction.

Figure 5A

Figure 5B

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Figure 7

Number of EUS-FNA passes: Most pancreatic EUS-FNA series report taking an average of three to four needle passes to make a definitive cytologic diagnosis of pancreatic cancer. The major determinant of the number of EUS-FNA passes needed to diagnose pancreatic adenocarcinoma is the differentiation of the tumor (23). Some well-differentiated tumors may take over ten separate passes to obtain enough diagnostic material. Although, performing this many passes may be frustrating for the endoscopist and cytopathologist, the consequences of a non-diagnostic aspirate may mean more procedures, including unnecessary surgery, for the patient. If a cytopathologist is not available to immediately assess the slides, then five to six passes of the lesion are recommended (23). However, this approach may produce non-diagnostic EUS-FNAs 15-20% of the time.

Aspiration tips: The ideal EUS-FNA specimen should produce just a few drops of slightly serosanguinous fluid, perhaps with a few particles of tissue visible within the specimen. If an aspirate just looks like pure blood, it is less likely to have much diagnostic material within it. Whether to use hard suction or minimal suction on the aspiration needle is a matter of preference in pancreatic EUS-FNA. My own approach is to usually use moderate suction initially for pancreatic masses (5 ml of suction in a 10 ml syringe). If I get a bloody pass with this approach, I make subsequent passes with minimal or no suction. Often just pulling back the needle trocar about 10 cm with each stroke or two of the needle in the tumor will provide enough suction to retrieve a diagnostic specimen. Whether using larger needles will increase diagnostic yields with the same degree of safety as 22 gauge needles is still unclear (38). Sometimes a few additional passes are needed to provide the cytopathologist with adequate material for special cytologic analyses (Figures 6 and 7). This most commonly occurs when the initial EUS-FNA suggests that the tumor may be something other than a pancreatic adenocarcinoma such as a lymphoma, islet cell tumor, or metastatic tumor. Lymphoma diagnosis by cell surface markers depends on obtaining enough viable tumor cells preserved in a special medium for cell-surface marker determination (42). If a cytopathologist is not present to warn the endosonographer that one of these diagnoses is suspected, then the EUS-FNA may result in an equivocal cytopathologic diagnosis for lack of adequate material for special processing.

EUS-FNA of Cystic Pancreatic Masses: EUS-FNA of cystic pancreatic lesions is different than for solid lesions. About 75% of cystic pancreatic lesions are pseudocysts (43). The goal of EUS and EUS-FNA is to differentiate truly benign lesions such as pseudocysts and serous cystadenomas from precancerous lesions such as mucinous cystadenomas (44) and intraductal papillary mucinous tumors (IPMT) (45) of the pancreas from frankly malignant cystadenocarcinomas (Figures 1 and 3). There are a number of studies demonstrating the endosonographic characteristics of these various cystic lesions (44-46); however, EUS-FNA continues to play a role especially in examining the suspicious multiseptated pancreatic cystic lesion. Obtaining a diagnostic cytology from malignant cystic lesions by just aspirating the cyst contents is low yield. If there is any solid component to the wall of a pancreatic cyst, this should be aspirated aggressively after draining the cyst contents. Chemical analysis of the cyst fluid has been studied extensively. Only an elevated cyst fluid carcinoembryonic antigen (CEA) seems to have any consistent predictive power in identifying likely mucinous cystadenomas and cystadenocarcinomas (44).

EUS-FNA for benign disease: EUS-FNA for benign disease other than pancreatic cystic lesions is still in its infancy. Although it appears to be safe, pancreatic EUS-FNA does not appear to add significantly to the diagnostic accuracy of EUS for chronic pancreatitis (47).

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Figure 9

COMPLICATIONS OF EUS-GUIDED FINE NEEDLE ASPIRATION
The overall complication rate of pancreatic EUS-FNA appears to be about 1-2% (4, 6, 10, 14-21, 23, 48), similar to that reported with CT, ultrasound-guided FNA, or biopsy. The major complications reported with EUS-FNA are bleeding, pancreatitis, and infection. Only one death has been reported to date with pancreatic EUS-FNA (10) which was uncontrollable bleeding after EUS-FNA using a radial echoendoscope. Extraluminal bleeding can actually be observed while doing EUS-FNA as an expanding echo-poor lesion adjacent to the aspirated lesion (49). In my own experience, bleeding is especially likely when the patient has portal hypertension from portal vein or splenic vein obstruction from the pancreatic neoplasm or when aspirating metastatic renal carcinoma to the pancreas (Figures 8-11). Pancreatitis after EUS-FNA is most likely to occur in patients already being evaluated for recurrent pancreatitis and when the FNA needle is passed through more than 2 cm to 3 cm of normal pancreas to obtain a specimen. Fortunately, bacteremia following EUS-FNA is quite uncommon (50); however, EUS-FNA of cystic pancreatic lesions has a higher risk of infectious complications (48). Because of this risk, broad-spectrum intravenous antibiotics during aspiration followed by a few days of oral antibiotics are routinely given for EUS-FNA of cystic pancreatic lesions. The risk of cancer seeding by EUS-FNA appears to be very low. I know of only one anecdotal case of documented EUS-FNA peritoneal seeding after aspirating a cystadenocarcinoma (Goldin SB, personal communication). Supporting the low incidence of peritoneal seeding with EUS-FNA is a recent interesting abstract (51) which reported a significantly lower incidence of peritoneal carcinomatosis after EUS-FNA of pancreatic cancers compared to percutaneous FNA.

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Figure 11A

Figure 11B

 

 

 

Summary

EUS-FNA is a powerful technique that has greatly impacted the role of EUS in the management of pancreatic masses (7). Pancreatic EUS-FNA is one of the most difficult of endosonographic techniques and should not be attempted by novice practitioners. However, in the hands of a skilled endosonographers, cytologically diagnostic samples should be obtainable in over 80% of pancreatic neoplasms with minimal morbidity.

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Editorial Board:
Manoop S. Bhutani, M.D.
Galveston, TX
William R. Brugge, M.D.
Boston, MA
Peter R. McNally, D.O.
Denver, CO
Iqbal S. Sandhu, M.D.
Salt Lake City, UT
Thomas J. Savides, M.D.
San Diego, CA

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