Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy in Esophageal Cancer

• Objectives
• Basic Principles
• Materials Used
• Description of the Procedure
• EUS-Guided FNA
• Limitations and Success Rate
• Limitations
• Success Rate
• Complications and Safety
• Indications
• References

Objectives

Accurate staging of esophageal cancer has important prognostic and management implications. Before the development of endoscopic ultrasound (EUS), esophageal cancers were staged by computed tomography (CT) and laparoscopy. EUS has since become an important imaging modality in determining the extent of locoregional spread of esophageal cancer and, in certain situations, distant metastasis. The addition of EUS-guided fine-needle aspiration (FNA) has only improved the accuracy of the procedure. Compared with CT, EUS-guided FNA is more accurate for local staging and results in a change in patient management in many cases [1]. Thus EUS and EUS-guided FNA have become an integral part of the preoperative staging algorithm for these patients.

The purpose of this paper is to discuss the indications for EUS-guided FNA in esophageal cancer, the methods and materials needed to perform FNA, the limitations of the procedure, and the contraindications to performing it.

Basic Principles

The prognosis of esophageal cancer remains poor with an overall 5-year survival of approximately 14 % [2]. Determining an optimal treatment strategy is dependent on the stage of the disease at the time of diagnosis. The main role of EUS and EUS-guided FNA is to provide staging information as most patients referred already have an established histological diagnosis. Occasionally, EUS-guided FNA is performed to diagnose an esophageal cancer; this situation may be encountered in patients whose esophageal tumors grow from the outer esophageal wall inward and subsequently appear as submucosal masses. Endoscopic biopsies are therefore usually nondiagnostic. In these situations, the primary tumor can be biopsied by EUS-guided FNA.

The first step in staging patients with esophageal cancer by EUS and EUS-guided FNA is patient selection. The procedure should only be offered to patients for whom its results may impact management. Therefore, patients who are not candidates for treatment because of co-morbidities or who have evidence of distant metastasis should not undergo the procedure.

Patients are staged according to the TNM classification system. Patients with EUS findings of tumor depth not extending beyond the muscularis propria (T2) (Figure [1]) and without nodal disease should undergo primary resection as preoperative chemotherapy has not shown a survival benefit. Patients with locally advanced tumors (T3, see Figure [2], [3], or N1, see Figure [4], [5]) may gain a survival advantage with combined neoadjuvant chemotherapy and radiation treatment prior to possible surgical resection [2].

EUS-guided FNA may also be helpful in detecting or diagnosing advanced disease not found on CT, such as pleural effusion, ascites [3], small liver lesions [4] [5], and celiac nodes [6], and this can alter management. For example, celiac nodes can be easily biopsied by EUS-guided FNA, given their proximity to the gastric wall (Figure [6]). If these nodes are positive they are considered to be M1a disease in esophageal tumors not involving the gastroesophageal junction, according to the most recent staging guidelines of the American Joint Commission on Cancer. These patients could then be spared surgery and be treated medically. Thus, the addition of EUS-guided FNA in esophageal cancer can have a major impact on the treatment of patients referred for esophageal cancer staging [1].

Materials Used

EUS-guided FNA is performed using a linear array echo endoscope (Figure [7]). The ultrasound transducer generates a 100°-180° image that is parallel to the shaft of the echo endoscope. Linear echo endoscopes have a switchable frequency range from 5 to 10 MHz. FNA can be carried out safely as the needle’s action can be tracked in its entirety, from exiting the biopsy channel to entering and aspirating the target lesion. Linear echo endoscopes provide color flow and Doppler information simultaneously with B-mode ultrasound. This facilitates the performance of FNA (the vascularity of the lesion is assessed) and the choice of a needle path that avoids vascular structures. Features of currently available linear echo endoscopes are summarized in Table [1].

The instruments are fitted with transparent balloons that are affixed to the tip of the echo endoscope and provide acoustic coupling when they are filled with water. FNA can be done using a variety of needle systems (e. g. Wilson Cook, GIP-Mediglobe, or Olympus) and sizes (range 19 - 25 gauge). The most common needle size is 22 gauge. A 10-ml syringe is used to aspirate the tissue specimen as the needle traverses the lesion.

Description of the Procedure

Often, standard endoscopy is performed prior to EUS to confirm the location and extent of the tumor, and the luminal diameter. If the endoscope cannot pass through the malignant stricture, dilation should be done. In general, serial dilation by up to three sizes (in 1-mm increments) is considered to carry a low risk for perforation. Dilation of the lumen to up to 14 mm (42 Fr) is generally required for passage of the linear echo endoscope to allow complete staging. Extremely stenotic tumors should not be aggressively dilated for staging purposes only, as perforation is substantially more frequent in these circumstances [7]. If the stricture is extremely stenotic, a probably safer alternative to aggressive dilation is sequential dilation over two separate procedures 24-48 hours apart.

EUS is done with the patient under conscious sedation, in a similar fashion to standard endoscopic procedures. One nurse is required for sedation and to monitor vital signs throughout the procedure. When FNA is to be carried out, an assistant who is knowledgeable about the procedure and the processing of the tissue samples is required. Ideally, given the complexity of the procedure and the knowledge needed to work synergistically with the endosonographer, dedicated EUS personnel (nurses and assistants) are involved.

EUS-Guided FNA

Maximizing the yield of FNA depends on prioritizing the sequence of FNA where there are multiple lesions, optimizing needle technique, the availability of on-site cytopathological interpretation, and avoiding complications.

The technique of EUS-guided FNA has been described previously [8] [9] [10]. The first step involves placement of the lesion to be biopsied in the center or just left of center of the imaging field. If there is a question about the presence of surrounding vascular structures, Doppler imaging can be used to confirm or exclude this, and it may be necessary to find a different needle track. Once the path has been determined, the needle is advanced through the biopsy channel of the endoscope and is seen exiting the biopsy channel into the lesion under real-time ultrasonography. Once it is in position, the central stylet is removed, a 10-ml syringe is attached to the hub of the needle, and suction is applied as to-and-fro movements are made within the lesion. Suction is then released and the needle is withdrawn. The cytological specimen is then sprayed onto glass slides that can be processed and immediately reviewed by a cytopathologist or cytotechnician if available. Otherwise, the material is fixed in ethanol and then processed for later review. If the first few passes reveal necrotic tissue, it may be necessary to target the periphery of the lesion to obtain a diagnosis.

The optimal technique for advancing the needle depends on three factors: (i) the consistency of the gastrointestinal wall; (ii) the size and consistency of the targeted lesion; and (iii) the proximity of surrounding vessels. In the esophagus, the wall is thin and taut, and so the needle can pass through without much resistance or elastic recoil. Therefore, very fine slow pincer movements are all that is required to advance the needle through the esophageal wall. When a patient has more than one lesion for biopsy, it becomes very important to prioritize lesions, to avoid contamination of the specimens and to improve the efficiency of the procedure. When a proximal esophageal cancer is staged for example, if a celiac lymph node or a liver lesion is found, this should be biopsied first because this would give information about the most advanced stage.

Limitations and Success Rate

Limitations

A major limitation to performing EUS-guided FNA arises when the tumor almost completely obstructs the esophageal lumen. In this situation, performing dilation to the extent that would allow the echo endoscope to pass would be unsafe. This may limit the ability to carry out FNA on possible liver lesions or celiac nodes, which could have a major impact on treatment.

Suspicious peritumoral lymph nodes typically are not sampled with EUS-guided FNA as a false-positive result can be obtained or dissemination of tumor into a benign lymph node can occur. There are currently no needle systems that completely avoid the possibility of contaminating the tissue aspirate when traversing the tumor to reach the lymph node. Given this pitfall, and the fact that most lymph nodes immediately adjacent to the tumor are malignant, we routinely avoid FNA in this situation. Tru-Cut needle biopsy with EUS guidance may overcome the limitation of the possibility of false-positive aspiration sampling from peritumoral lymph nodes.

Success Rate

EUS has been proven to be the most accurate method for staging of esophageal cancer with a tumor (T)-staging accuracy of 85 % and lymph node (N)-staging accuracy of 75 %. The addition of EUS-guided FNA to the procedure has increased N-staging accuracy to greater than 90 % [11] [12]. Ideally, a maximal procedural yield is obtained if there are on-site cytopathology facilities to determine specimen adequacy and provide a preliminary diagnosis [13]. Given that a cytopathologist may not be available to provide immediate interpretation, usually two or three FNA passes are sufficient for diagnosis of lymph nodes and one or two passes for a liver lesion.

Re-staging of esophageal cancer after neoadjuvant treatment by EUS is controversial. This is because post-treatment inflammatory and fibrotic changes mimic the appearance of residual tumor. We have found, however, that EUS-guided FNA can be very helpful in re-staging. For example, patients who appear, from endoscopic and biopsy findings, to have had a complete response to neoadjuvant therapy may not be inclined to proceed with an esophageal resection. If EUS-guided FNA were to confirm the presence of a positive lymph node or residual tumor deep in the esophageal wall, this would support proceeding with esophagectomy. Conversely, if a celiac lymph node or liver lesion were to be found on EUS-FNA, medical management might be favored.

Complications and Safety

The most common complications related to FNA include hemorrhage, infection, and perforation. When complications do occur secondarily to EUS-guided FNA, they generally happen within the first 24 hours. A large study of 322 patients undergoing EUS-guided FNA reported an overall complication rate of 1.6 % [14].

A recently published prospective study to assess the risk of bacteremia during EUS-guided FNA of upper gastrointestinal solid lesions found no increase in the rate when the procedure was compared with diagnostic endoscopy [15]. Therefore, prophylactic antibiotics are not routinely given.

Clinically significant bleeding after FNA is extremely rare. To avoid hemorrhagic complications associated with FNA, color and pulsed Doppler imaging can help to identify a needle track that avoids vascular structures. When bleeding does occur, it can be recognized immediately on EUS. Intervention should be considered when there is expansion of the hematoma.

Clinically significant perforations resulting from FNA needle passes are extremely rare. Most reported cases of perforation with EUS are related to dilation, endoscope trauma, or both. There are rare reports of hypopharyngeal or cervical perforations occurring during intubation with the echo endoscope; these may be caused by the longer rigid tip on echo endoscopes. Therefore, in elderly patients with possible cervical stenosis, extra caution is warranted during intubation with the endoscope. In addition, care should be taken when passing the echo endoscope beyond the duodenal bulb, as this is another site where perforation has been described.

Indications

Necessary. EUS-guided FNA, CT, and positron emission tomography (PET) can be used to stage esophageal cancer. EUS-guided FNA is more accurate than CT for locoregional staging and is the preferred modality for sampling posterior mediastinal or celiac lymph nodes visualized on CT and/or PET. EUS-guided FNA is sometimes necessary to diagnose esophageal cancer in intramural or submucosal tumors where previous biopsies have been nondiagnostic.

Appropriate. EUS-guided FNA is appropriate in patients who are surgical candidates and who do not have evidence of distant metastases or lymph nodes on CT and/or PET. EUS-guided FNA is also appropriate in re-staging tumors following neoadjuvant treatment, to assess the tumor response.

Inappropriate. EUS-guided FNA should not be performed when the information provided will not influence patient management. EUS-guided FNA also should not be carried out in patients who have a contraindication to endoscopy, have an uncorrected coagulopathy, or have vascular structures between the target lesion and the lumen that preclude safe passage of the needle.

References

• 1 Chang K J, Soetikno R M, Bastas D. et al . Impact of endoscopic ultrasound combined with fine-needle aspiration biopsy in the management of esophageal cancer.  Endoscopy. 2003;  35 962-966
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Walsh T N, Noonan N, Hollywood D. et al . A comparison of multimodal therapy and surgery for esophageal adenocarcinoma [see comments].  NEJM. 1996;  335 462-467
  CrossrefPubMedSearch in Google Scholar
• 3 Nguyen P, Chang K J. Endoscopic ultrasound (EUS) in the detection of ascites and EUS-guided paracentesis.  Gastrointest Endosc. 2001;  54 336-339
  CrossrefPubMedSearch in Google Scholar
• 4 Nguyen P, Feng J C, Chang K J. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions.  Gastrointest Endosc. 1999;  50 357-361
  CrossrefPubMedSearch in Google Scholar
• 5 Prasad P, Schmulewitz N, Patel A. et al . Detection of occult liver metastases during EUS for staging of malignancies.  Gastrointest Endosc. 2004;  59 49-53
  CrossrefPubMedSearch in Google Scholar
• 6 Parmar K S, Zwischenberger J B, Reeves A L, Waxman I. Clinical impact of endoscopic ultrasound-guided fine needle aspiration of celiac axis lymph nodes (M1a disease) in esophageal cancer.  Ann Thorac Surg. 2002;  73 916-920; discussion 920-921
  CrossrefPubMedSearch in Google Scholar
• 7 Van Dam J, Rice T W, Catalano M F. et al . High-grade malignant stricture is predictive of esophageal tumor stage. Risks of endosonographic evaluation.  Cancer. 1993;  71 2910-2917
  PubMedSearch in Google Scholar
• 8 Chang K J, Katz K D, Durbin T E. et al . Endoscopic ultrasound-guided fine-needle aspiration.  Gastrointest Endosc. 1994;  40 694-699
  PubMedSearch in Google Scholar
• 9 Wiersema M J, Kochman M L, Cramer H M. et al . Endosonography-guided real-time fine-needle aspiration biopsy.  Gastrointest Endosc. 1994;  40 700-707
  PubMedSearch in Google Scholar
• 10 Vilmann P, Hancke S, Henriksen F W, Jacobsen G K. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract.  Gastrointest Endosc. 1995;  41 230-235
  PubMedSearch in Google Scholar
• 11 Vazquez-Sequeiros E, Norton I D, Clain J E. et al . Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma.  Gastrointest Endosc. 2001;  53 751-757
  CrossrefPubMedSearch in Google Scholar
• 12 Vazquez-Sequeiros E, Wiersema M J, Clain J E. et al . Impact of lymph node staging on therapy of esophageal carcinoma.  Gastroenterology. 2003;  125 1626-1635
  CrossrefPubMedSearch in Google Scholar
• 13 Klapman J B, Logrono R, Dye C E, Waxman I. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration.  Am J Gastroenterol. 2003;  98 1289-94
  CrossrefPubMedSearch in Google Scholar
• 14 O’Toole D, Palazzo L, Arotcarena R. et al . Assessment of complications of EUS-guided fine-needle aspiration.  Gastrointest Endosc. 2001;  53 470-474
  CrossrefPubMedSearch in Google Scholar
• 15 Levy M J, Norton I D, Wiersema M J. et al . Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNA.  Gastrointest Endosc. 2003;  57 672-678
  CrossrefPubMedSearch in Google Scholar

K. J. Chang, M. D.

Gastrointestinal Oncology, Comprehensive Digestive Disease Center, University of California, Irvine Medical Center

101 The City Drive, Building 22C · First Floor, Room 106 · Orange, CA 92868-3298 · USA

Fax: +1-714-456-520

Email: kchang@uci.edu

References

• 1 Chang K J, Soetikno R M, Bastas D. et al . Impact of endoscopic ultrasound combined with fine-needle aspiration biopsy in the management of esophageal cancer.  Endoscopy. 2003;  35 962-966
  Thieme ConnectPubMedSearch in Google Scholar
• 2 Walsh T N, Noonan N, Hollywood D. et al . A comparison of multimodal therapy and surgery for esophageal adenocarcinoma [see comments].  NEJM. 1996;  335 462-467
  CrossrefPubMedSearch in Google Scholar
• 3 Nguyen P, Chang K J. Endoscopic ultrasound (EUS) in the detection of ascites and EUS-guided paracentesis.  Gastrointest Endosc. 2001;  54 336-339
  CrossrefPubMedSearch in Google Scholar
• 4 Nguyen P, Feng J C, Chang K J. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions.  Gastrointest Endosc. 1999;  50 357-361
  CrossrefPubMedSearch in Google Scholar
• 5 Prasad P, Schmulewitz N, Patel A. et al . Detection of occult liver metastases during EUS for staging of malignancies.  Gastrointest Endosc. 2004;  59 49-53
  CrossrefPubMedSearch in Google Scholar
• 6 Parmar K S, Zwischenberger J B, Reeves A L, Waxman I. Clinical impact of endoscopic ultrasound-guided fine needle aspiration of celiac axis lymph nodes (M1a disease) in esophageal cancer.  Ann Thorac Surg. 2002;  73 916-920; discussion 920-921
  CrossrefPubMedSearch in Google Scholar
• 7 Van Dam J, Rice T W, Catalano M F. et al . High-grade malignant stricture is predictive of esophageal tumor stage. Risks of endosonographic evaluation.  Cancer. 1993;  71 2910-2917
  PubMedSearch in Google Scholar
• 8 Chang K J, Katz K D, Durbin T E. et al . Endoscopic ultrasound-guided fine-needle aspiration.  Gastrointest Endosc. 1994;  40 694-699
  PubMedSearch in Google Scholar
• 9 Wiersema M J, Kochman M L, Cramer H M. et al . Endosonography-guided real-time fine-needle aspiration biopsy.  Gastrointest Endosc. 1994;  40 700-707
  PubMedSearch in Google Scholar
• 10 Vilmann P, Hancke S, Henriksen F W, Jacobsen G K. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract.  Gastrointest Endosc. 1995;  41 230-235
  PubMedSearch in Google Scholar
• 11 Vazquez-Sequeiros E, Norton I D, Clain J E. et al . Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma.  Gastrointest Endosc. 2001;  53 751-757
  CrossrefPubMedSearch in Google Scholar
• 12 Vazquez-Sequeiros E, Wiersema M J, Clain J E. et al . Impact of lymph node staging on therapy of esophageal carcinoma.  Gastroenterology. 2003;  125 1626-1635
  CrossrefPubMedSearch in Google Scholar
• 13 Klapman J B, Logrono R, Dye C E, Waxman I. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration.  Am J Gastroenterol. 2003;  98 1289-94
  CrossrefPubMedSearch in Google Scholar
• 14 O’Toole D, Palazzo L, Arotcarena R. et al . Assessment of complications of EUS-guided fine-needle aspiration.  Gastrointest Endosc. 2001;  53 470-474
  CrossrefPubMedSearch in Google Scholar
• 15 Levy M J, Norton I D, Wiersema M J. et al . Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNA.  Gastrointest Endosc. 2003;  57 672-678
  CrossrefPubMedSearch in Google Scholar

K. J. Chang, M. D.

Gastrointestinal Oncology, Comprehensive Digestive Disease Center, University of California, Irvine Medical Center

101 The City Drive, Building 22C · First Floor, Room 106 · Orange, CA 92868-3298 · USA

Fax: +1-714-456-520

Email: kchang@uci.edu