Interventional Endoscopic Ultrasonography

Kenji Yamao; Vikram Bhatia; Nobumasa Mizuno; Akira Sawaki; Yasuhiro Shimizu; Atsushi Irisawa

Disclosures

J Gastroenterol Hepatol. 2009;24(4):509-519. 

In This Article

II. EUS-FNA

(1) Indications and Contraindications

A fundamental principle of EUS-FNA is that the information obtained should have the potential to affect patient management.[5] In addition, the indications for EUS-FNA should be guided by its diagnostic accuracy, cost effectiveness, and patient comfort and safety. Erickson[6] proposed that the following 'clear indications' for EUS-FNA: 1) Sampling of pancreatic masses when other techniques have failed, 2) Sampling of computed tomography (CT)-detected mediastinal adenopathy when other techniques have failed, 3) Sampling, at the time of diagnostic or staging EUS, of lesions that are poorly seen by or inaccessible to biopsy by other imaging modalities.

In Japan, the current indications for EUS-FNA include:[7,8] (i) differentiating between benign and malignant lesions; (ii) staging of cancer; (iii) histological evidence of malignancy before chemotherapy and/or radiation therapy.

Recently, the utility of EUS-FNA making an etiological diagnoses has been reported. Examples include characterization of histological subtypes of rare forms of pancreatic cancer,[9] inflammatory pancreatic mass[10] or autoimmune pancreatitis,[11,12] gastrointestinal stromal tumor (GIST),[13,14] subtypes of malignant lymphoma,[15] sarcoidosis and so on. Such diagnoses are based on one or more of histological (H&E staining), immunohistochemical or genetic analysis.

According to these indications, the potential uses for EUS-FNA include,[5] (i) pancreatic mass; (ii) mediastinal lymph nodes (metastasis from esophageal and lung cancer); (iii) celiac lymph node in association with a known upper gastrointestinal (GI) cancer or in a patient suspected of having cancer or lymphomam; (iv) intra-abdominal lymph nodes in association with a known (or suspicion of) cancer; (v) peri-rectal lymph node/mass; (vi) posterior mediastinal mass of unknown etiology, and (vii) intrapleural/intra-abdominal fluid. In addition to these lesions , the indications for EUS-FNA[6,16] have been expanded to peri-pancreatic masses, submucosal masses, liver lesions, left adrenal masses, suspected recurrent cancers in and adjacent to surgical anastomosis.

Contraindications to EUS-FNA include situations in which the FNA result would not affect management, inability to clearly visualize a lesion, a tumor mass or vessel interposed in the path between the needle and target, bleeding diathesis, and risk of tumor seeding.[5,6,16]

(2) Equipment for EUS-FNA

A curved linear array echoendoscope (convex echoendocope) is usually available for EUS-FNA. This instrument generates longitudinal sector images parallel to the axis of the endoscope and is equipped with color Doppler functioning.[17] At present, the most important function of the echoendoscope is as a large instrument channel that allows not only histological biopsies to be taken, but also therapeutic applications.

Several needles have been developed. Recent models for EUS-FNA consist of a steel needle and can be lure-locked in a fixed position on the echoendoscope. The endoscopist can then advance the needle into the lesion himself or herself under ultrasonic guidance. Using the newly developed automated biopsy device, EUS FNA procedures are easier to perform and sufficient diagnostic material can be obtained more readily.[18] As to needle technology, the shapes of the tips and the diameter of the needle have been continuously developed and improved. Needles range from 19- to 22- gauge and allow a depth of penetration of up to 10 cm to be obtained[17] and recently, a 25-gauge needle is also available. A large size 19-guage trucut needle is also now commercially available.[19,20] Specimens obtained by such a trucut needle can easily be processed for immunohistochemical and gene analyses.

(3) Technique of EUS-FNA

Detailed steps of EUS-FNA procedures have been described in several articles.[21–23] Papanicolaou and Giemsa stains have been adopted as conventional cytological stains for the aspirates obtained. Sufficient tissue enables processing for HE stains, immunohistochemical stains, and flow cytometry[24] as well as gene analysis.[10,25,26]

One of the most important issues may be the introduction of rapid staining performed by a cytopathologist or cytotechnician during the procedure. Aspirated materials mixed with blood are usually prepared on slides or placed directly into a fixative for H&E staining. When a cytopathologist or cytotechnician is in attendance, the aspired material is spread onto a plate, picked up with tweezers and sprayed onto glass slides.[27] One slide is air-dried for on-site interpretation, the other slide is fixed in ethanol for Papanicolaou staining. Any remaining material goes into a fixative or cell preservative for later cell block preparation for H&E staining or immunohistochemical staining.

Erickson et al.[28] reported that failure to have a cytopathologist in attendance increases the number of passes, reduces definitive cytological diagnoses, prolongs procedure time, increases risk and consumes additional needles. If a cytopathologist or a cytotechnician is not in attendance, three passes should be taken through lymph nodes and five to six passes through pancreatic masses to ensure adequate cellularity in >90% of cases.[28]

Most endoscopists believe that histopathology is a more sensitive technique than cytology to obtain histological evidence of gastrointestinal cancers (esophagus, stomach and colon). Furthermore, cytology is considered unnecessary when an endoscopic biopsy is available. However, cytology (or FNA) has been reported to be an equally or more sensitive technique than histopathology in the diagnosis of breast or thyroid cancer,[29] and cytology has also been determined to be a SAFE (safe, accurate, fast and economic) technique.[30] The present authors and our colleagues previously reported that the cytology was more accurate than histopathology in EUS-FNA for the differential diagnosis of pancreatic mass lesions.[10] However, the usefulness of histopathology combined with immunohistochemical analysis to determine specific etiology has been reported.[9] Thus, a system in which both cytology and histopathology are available, needs to be developed.

With these refinements of instruments and technical skills, EUS followed by EUS-FNA is expected to be performed on a routine basis in high volume centers throughout the Asia-Pacific region and elsewhere internationally.

(4) Diagnostic Accuracy and Complications

High rates of adequate tissue sampling and diagnostic accuracy have been reported for EUS-FNA. Among nearly 1700 patients, the accuracy, sensitivity and specificity of EUS-FNA for pancreatic tumors were 88%, 85% and 98%, respectively.[31] Likewise, EUS-FNA for lymph nodes found a sensitivity of 92%, a specificity of 93% and an accuracy of 92%.[32]

The overall complication rate of EUS-FNA appears to be 1 to 2%.[33] The major complications reported with EUS-FNA are infections in cystic lesions, bleeding, pancreatitis, and duodenal perforation.[34] In a large multi-center trial involving 554 consecutive mass or lymph node biopsies, only 5 complications (2 perforations, 2 febrile episodes, 1 hemorrhage) were observed; none were fatal.[32] Cystic pancreatic lesions appear to have a greater risk of infective complications than solid pancreatic masses. Two deaths have been reported with EUS-FNA. One patient developed fulminant cholangitis associated with EUS-FNA of a liver metastasis, the other developed uncontrolled bleeding from a pseudoaneurysm after EUS-FNA of the pancreas.[6] The present authors have experienced EUS-FNA related severe complications, including one massive bleeding from a gastric GIST,[35] one rupture of a pancreatic pseudoaneurysm followed by massive gastrointestinal bleeding, and one acute portal vein obstruction.[36] The last two cases might possibly have been caused by acute focal pancreatitis.

The risk of acute pancreatitis after EUS-FNA of pancreatic masses has been estimated in 19 centers. It was found to have a frequency of 0.29% in a retrospective analysis, and 0.64% in prospective study.[37] Thus, although EUS-FNA for pancreatic lesions has been evaluated to be a good indicator for further treatment, largely due to the high technical reliability of pancreatic tissue sampling, the possibility of severe complications needs to be carefully considered.

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