Staging and Staging Modalities

Mediastinal lymph node metastases are present in nearly half of all patients with NSCLC. Accurate staging of NSCLC is crucial in determining treatment options because the detection of mediastinal lymph node metastasis preoperatively has therapeutic implications. In the absence of distant metastasis, the documentation of mediastinal metastasis is probably the most common deterrent to cure.^15–26 The TNM staging system used for lung cancer (see Box 31.1) designates ipsilateral peribronchial, intrapulmonary, or ipsilateral hilar lymph nodes as N1 disease and ipsilateral mediastinal and subcarinal lymph node involvement as N2 disease. Although N2 disease is potentially resectable, most patients with N2 disease receive multimodality treatment. Contralateral lymph node involvement of mediastinal or hilar nodes or either ipsilateral or contralateral scalene or supraclavicular lymph nodes is designated N3 disease, which precludes resection (Table 31.1 and Fig. 31.1, and see Box 31.1).^{12–14,26,27}

Table 31.1 Lymph Node Map Definitions

From Mountain CF, Dresler CM: Regional lymph node classification for lung cancer staging. Chest 11:1718–1723, 1997.

Fig. 31.1 Lymph node stations.

(From Mountain CF, Dresler CM: Regional lymph node stations for lung cancer staging. Chest 111:1718–1723, 1997.)

Various techniques are currently available to diagnose and stage lung cancer, including plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), endobronchial ultrasound (EBUS), and EUS. CT scan of the chest is the current standard by which mediastinal lymphadenopathy is detected. Generally, lymph nodes larger than or equal to 1 cm on chest CT scan are considered abnormal. A review of previously published studies reveals an accuracy of CT staging of the mediastinum of 52% to 88%.^28–38 This variation has been attributed to the wide range of correlation of lymph node size to the presence of malignant involvement. Although the general trend is increased risk for metastasis correlating with increasing lymph node size, lymph node size is not an accurate criterion for assessing risk. Problems associated with size as a criterion include the inability to differentiate inflammatory or reactive lymph nodes from malignant involvement. In one study, 37% of mediastinal lymph nodes that ranged in size from 2 to 4 cm were benign,³⁸ and 40% of enlarged nodes in another series were not cancerous.³⁹ Similarly, normal-sized lymph nodes can contain foci of cancer. McKenna and colleagues⁴⁰ found no correlation between the presence of mediastinal nodal metastases and nodal size. Metastases may be found in 21% of normal-sized nodes.⁴¹

MRI may be slightly superior to CT in the detection of mediastinal disease,⁴² and PET has been shown to be superior to CT for staging for the mediastinum.^43,44 PET does not rely on an arbitrary cutoff of size to diagnose malignant nodes but detects the increased glycolytic rate in metabolically active tumors. In a meta-analysis, PET had a sensitivity of 79% and a specificity of 91% compared with CT, which had sensitivity and specificity of 60% and 77%, for the detection of mediastinal disease.⁴³ In another meta-analysis by Toloza and colleagues,⁴⁴ the performance characteristics of CT, PET, and EUS for staging the mediastinum in NSCLC were compared. PET was more accurate than CT or EUS for detecting mediastinal metastases with a sensitivity of 84% and a specificity of 89% for PET compared with CT (sensitivity 57% and specificity 82%) and EUS (sensitivity 78% and specificity 71%). However, PET is limited for small lesions (≤1 cm), has false-negative results in tumors with low metabolic activity, and has false-positive results in benign lesions such as granulomatous disease. Although PET has a relatively high sensitivity, because of the importance and implications of staging, specificity is still too low, and pathologic staging is still generally sought.^45–47

Fritscher-Ravens and associates⁴⁸ performed a prospective comparison of CT, PET, and EUS for the detection of metastatic lymph nodes metastases in patients with lung cancer being considered for operative resection. After bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement with bronchoscopic biopsy and cytology–proven (n = 25) or radiologically suspected (n = 8) lung cancer before surgery. Surgical histology was used as the “gold standard” and revealed NSCLC in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%; specificities were 74%, 83%, and 71%; and accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity 81%, specificity 94%, accuracy 88%). The specificity of EUS (71%) was improved to 100% by fine needle aspiration (FNA) cytology. The authors concluded that no single imaging method alone was conclusive in evaluating potential mediastinal involvement. They also suggested that CT may be necessary to evaluate the pretracheal region and the rest of the thorax and that PET may be valuable to detect distant metastases.

Whenever enlarged lymph nodes are seen in the mediastinum on chest CT scan, standard practice is to perform a lymph node biopsy for more accurate staging. The traditional methods for performing a lymph node biopsy are via CT or bronchoscopy or both. Bronchoscopy with FNA is commonly used to evaluate suspicious paratracheal, hilar, and subcarinal lymph nodes seen on CT.^49–52 The role of bronchoscopy in the diagnosis and staging of NSCLC is well established and has a sensitivity of approximately 60%.^53–59 Bronchoscopy is unable to access the aortopulmonary window or the inferior mediastinal nodes, however. CT-guided biopsy of the mediastinum is limited by overlying vascular and bony structures. When the lymph node status is not determined with CT or bronchoscopy or both, mediastinoscopy and in some cases limited thoracotomy are performed to clarify the disease stage.^37,60–62 However, these procedures are more invasive and require general anesthesia and inpatient recovery, increasing the time, cost, and risk of the staging process.⁶³

Endoscopic Ultrasound

The advent of EUS has made it possible to image the GI tract and surrounding extraluminal structures such as the mediastinum with precise resolution. EUS has played an increasingly important role as an accurate and safe method for staging patients with NSCLC.^64–85 With the advent of transesophageal EUS-guided FNA, suspicious posterior mediastinal lymph nodes, including aortopulmonary window, subcarinal, and inferior (below carina) paraesophageal nodes, can be sampled. Tracheal air artifact generally precludes reliable assessment of the anterior mediastinum lesions, pretracheal nodes, and upper paratracheal nodes; however, the advent of EBUS technology seems to be minimizing this limitation. The use of EUS and EBUS technology can enhance the overall accuracy for detecting mediastinal lymph node metastasis.

The results of an early pilot study evaluating the role of EUS in 17 patients with lung cancer found EUS to be very accurate at detecting mediastinal lymphadenopathy with an overall accuracy of 71% versus 41% for CT.⁸³ However, the capability of performing EUS-guided FNA was unavailable during this initial study. Sampling of suspicious lymph is essential except in N1 nodes. In the 1990s, several prospective studies evaluated the accuracy of EUS, EUS-guided FNA, and chest CT scan in detecting and staging mediastinal lymph node metastasis in patients with NSCLC based on correlation with surgical staging.^69,70,75 Gress and colleagues⁷⁵ reported a study consisting of patients with NSCLC and enlarged mediastinal lymph nodes (>1 cm) seen on chest CT scan. EUS-guided FNA was performed for suspicious contralateral posterior mediastinal or subcarinal lymph nodes. EUS criteria used to differentiate benign from malignant lymph nodes resulted in an accuracy of 84% compared with 49% for CT. The sensitivity and specificity of CT was 64% and 35%, which compared with a sensitivity and specificity of 86% and 83% for EUS. The addition of transesophageal EUS–guided FNA improved the overall accuracy of lymph node staging to 96% with a sensitivity of 93% and a specificity of 100%. The combination of CT and EUS did not improve overall accuracy above that for EUS alone for detecting lymph node involvement. However, the addition of CT aided in evaluating the extent of the lung cancer, detecting distant metastasis not seen by EUS and evaluating anterior and pretracheal nodes, which are not imaged by EUS. EUS was best at accurately detecting mediastinal lymph node metastasis in the aortopulmonary window (station 5), subcarinal (station 7), and paraesophageal (station 8) regions (see Fig. 31.1).

These findings are similar to the studies reported by Giovannini and colleagues⁷³ and Silvestri and coworkers,⁷⁴ who reported sensitivities of 81% and 89% and specificities of 100% each. A recent meta-analysis by Micames and colleagus⁶⁷ showed a pooled sensitivity of 83% and a pooled specificity of 97% for EUS-FNA staging of NSCLC.

Although still not approaching the “gold standard” of mediastinoscopy and lymph node biopsy, EUS-FNA has greatly improved minimally invasive staging of NSCLC. As noted earlier, where EUS fails is in the anterior mediastinum where tracheal air artifact generally precludes reliable assessment of the anterior mediastinum lesions, pretracheal nodes, and upper paratracheal nodes. In an attempt to view the anterior mediastinum, radial EBUS was initially developed in the 1990s. There was limited use of the technology, however, because it was impossible to perform real-time guided FNA of lesions. In more recent years, convex, linear probe technology has been developed and now allows for real-time EBUS-guided transbronchial needle aspiration (TBNA). A systematic review of EBUS-TBNA showed that it was a safe and effective modality to aid in the staging of NSCLC with a sensitivity ranging from 85% to 100% without reported complications.⁶⁸ Gu and colleagues⁶⁹ performed a meta-analysis of studies aimed at measuring EBUS-TBNA accuracy and found a 93% sensitivity and 100% specificity in detecting mediastinal lymph node metastasis. Given the high sensitivity and specificity of both EUS-FNA and EBUS-FNA, many investigators have been seeking to perform a complete, “medical mediastinoscopy,” with the hope of avoiding the more traditional, invasive staging, including mediastinoscopy, of NSCLC before operative intervention.

The largest study to date was performed by Wallace and colleagues,⁷⁰ who compared the use of TBNA, EUS-FNA, and EBUS-TBNA using pathologic confirmation of malignancy or benign disease as the diagnostic standard. This group found EBUS-FNA to be more sensitive, with a higher negative predictive value than TBNA. More importantly, they found the combination of EBUS-FNA with EUS-FNA to have a sensitivity of 93%, a positive predictive value of 100%, and a negative predictive value of 97%. These results suggest that EBUS-FNA may complement EUS-FNA and possibly could provide near-complete, minimally invasive staging of the mediastinum in patients with NSCLC. These combined modalities may eventually eliminate the need for mediastinoscopy or other invasive surgical procedures for staging purposes.

Endoscopic Ultrasound Technique for Imaging the Mediastinum

After informed consent is obtained, the patient is placed in the left lateral decubitus position. Conscious sedation is administered, and the echoendoscope is passed to the gastroesophageal (GE) junction in a manner similar to the passage of a duodenoscope. Many endosonographers first perform staging with a radial scanning echoendoscope and then switch to a dedicated biopsy echoendoscope or a curved linear array echoendoscope if FNA is to be performed.

When imaging the mediastinum, a thorough understanding of mediastinal anatomy relative to the esophagus is essential to perform a complete examination. Scanning should begin distally below the GE junction while withdrawing the scope proximally because this limits scanning artifacts. It is useful to press the transducer with its balloon partially inflated against the gut wall to minimize air artifacts and help to anchor the transducer. In addition, the suction port is depressed to maintain optimal imaging by minimizing intraluminal air.

As the endosonographer withdraws the radial scanning echoendoscope, the aorta should be maintained in the 5 o’clock to 6 o’clock position in the ultrasound field, which generally allows proper orientation of the paraesophageal structures. The aorta is easily recognized as a circular anechoic structure, approximately 1.5 to 2 cm in diameter, with a relatively bright border resulting from back wall enhancement (a normal artifact seen in vessels). As the echoendoscope is withdrawn into the distal esophagus, the aorta, spine, left lobe of the liver, inferior vena cava, and heart can be seen. The spine is also easily identified in the 7 o’clock position next to the aorta and has irregular echo features with artifacts produced by poor penetration of echoes through bony structures. The left lobe of the liver appears at the 6 o’clock to 12-o’clock position, and often the hepatic veins and inferior vena cava can be seen as they course through the liver. Slightly more proximally, the beating of the heart is appreciated as the left atrium comes into view at the 12 o’clock position. The mitral valve leaflets can be seen as the valve opens from the left atrium into the left ventricle, and the pulmonary veins can be seen entering the left atrium. The left pulmonary artery arches posteriorly to the left of the ascending aorta and tends to be easier to view than the right pulmonary artery, which can be seen just below the carina. The left ventricle, right atrium, and right ventricle lie deep to the left atrium; it can be more difficult to visualize these structures completely. As the aorta moves toward the left, the spine and azygos vein are seen posteriorly. The aortic outflow tract can be appreciated as the endoscope is withdrawn further. The spine continues to be a useful landmark because it consistently appears as a hyperechoic structure located posteriorly throughout the chest. Careful inspection of this area may reveal the thoracic duct adjacent to the aorta and spine.

The right lung appears as hyperechoic rings emanating from the 9 o’clock position, whereas the left lung appears at the 2 o’clock position. In the midesophagus, the right and left bronchi are easily demarcated by the hyperechoic rings (echogenic air) seen at the 11 o’clock and 1 o’clock positions. The two bronchi join together to form the trachea normally at 27 to 28 cm from the incisors. The azygos vein can be seen coming into position to the right of the aorta and moves anterior to the spine and toward the right lung. As the endoscope is withdrawn further, the azygos vein can be seen to move forward and extend anteriorly into the superior vena cava. The ascending aorta can be difficult to trace because this structure runs deep to the hilar structures (pulmonary vessels), and because of air within the bronchi and trachea, the ascending aorta is often not fully imaged. In the proximal esophagus, the aortic arch is identified on the left and moves rightward and anteriorly across the screen. In the cervical esophagus, above the level of the aortic arch, the carotid vessels and, occasionally, the thyroid gland can be seen (Figs. 31.2, 31.3, and 31.4).

Fig. 31.2 A, Radial imaging at the distal esophagus showing the liver, inferior vena cava (IVC), and aorta (AO). The spine lies immediately deep to the aorta. B, Imaging slightly higher in the distal esophagus showing the right lower lobe of the lung (RLL), left lung (LL), aorta (AO), spine (SP), and a portion of the left atrium (LA).

Fig. 31.3 Radial endoscopic ultrasound (EUS) from the distal esophagus. The left atrium (LA), right atrium (RA), right ventricle (RV), and left ventricle (LV) can be seen. The leaflets of the mitral valve and the base of the aortic outflow tract (AOFT) are also visible.

Fig. 31.4 Radial endoscopic ultrasound (EUS) from the most proximal aspect of the esophagus. The left common carotid artery (LCA), left internal jugular vein (LIJ), right internal jugular vein (RIV), right common carotid artery (RCA) are seen. In addition, the thyroid gland is seen on either side of the trachea (TR).

Evaluation of the mediastinum using linear EUS requires rotation of the echoendoscope every few centimeters for a thorough evaluation. As in radial EUS, vascular structures provide the major landmarks for orientation, and the home base structure is the descending aorta, which is first located approximately 35 cm from the incisors. The echoendoscope is rotated initially clockwise (right) bringing structures anterior to the esophagus into view and then counterclockwise (left) bringing posterior structures into view. The left atrium is found by rotating the shaft of the scope 180 degrees in the distal esophagus to midesophagus until a large, echolucent structure is seen within which the mitral valve leaflets are located. By tipping the scope upward and with slight withdrawal, the subcarinal lymph node station is located immediately beneath the endoscope at approximately 27 cm between the left atrium and right pulmonary artery. The aortopulmonary window is located by following the descending aorta cephalad to the arch and pushing the endoscope in again about 2 cm. The endoscope is turned 90 degrees clockwise and tipped up slightly until a cross-sectional view of the aortic arch and the more distally located left pulmonary artery are seen. The area between these structures is known as the “AP window.” Another potentially important area for FNA of lymph nodes is the celiac axis. This area is located by finding the abdominal aorta at the level of the GE junction and the takeoff of the celiac artery with the superior mesenteric artery just distal to this (Figs. 31.5 and 31.8).

Fig. 31.5 A, Linear array imaging of the celiac axis is depicted showing the takeoff of the superior mesenteric artery (SMA) and celiac axis (CX) along with the hepatic artery (HA) and splenic artery (SA) branches. B, More typical linear images as seen from the proximal stomach. C, Radial imaging showing the celiac axis.

Fig. 31.6 A, Curved linear array view through the midesophagus of the subcarinal (SC) region. The left atrium (LA) is next to the right pulmonary artery (PA) with the ascending aorta lying deep to these structures. B, Linear array view through the midesophagus of the aortic arch (AA) and the pulmonary artery (PA)—the “AP window.” C, Radial imaging of the area of the AP window.

Fig. 31.7 A, Mediastinal lymph node (LN) as imaged with the linear array endoscopic ultrasound (EUS) system. B, The fine needle aspiration (FNA) needle is seen exiting the scope; the tip of the needle is seen to be in the center of the LN. C, High-power magnification of hematoxylin and eosin stain on cell block reveals metastatic adenocarcinoma. D, High-power magnification of immunoperoxidase stain on cell block. Tumor nuclei (arrows) are positive for TTF1 antibody consistent with non–small cell lung carcinoma.

Fig. 31.8 Linear endoscopic ultrasound (EUS) reveals a hypoechoic mass within the mediastinum. EUS-guided fine needle aspiration (FNA) was performed and revealed metastatic non–small cell lung cancer (cytology favored a large cell neuroendocrine-type lesion).

Mediastinal Lymph Nodes

EUS-guided FNA became available after the development of a specially designed needle catheter system consisting of a 4-cm, 23-gauge needle attached to a 180-cm long, 5-Fr aspiration catheter (Echo-Tip; Wilson-Cook Medical, Inc, Winston-Salem, NC) and the 22-gauge, 10-cm needle (GIP, Medi-Globe, Inc, Tempe, AZ). At the present time, several EUS catheter–FNA needle systems are available with various needle lengths (up to 14 cm) and gauges (19-gauge to 25-gauge) available. We routinely perform EUS-guided FNA on all posterior mediastinal lymph nodes that are suspicious for malignant involvement by clinical suspicion or EUS criteria or both. Many patients have more than one suspicious lymph node or finding. In our patients, we sample only the most suspicious lymph node or finding that would have the greatest impact on the clinical staging (i.e., contralateral or subcarinal).

The EUS-guided FNA biopsy technique was initially developed for use with the linear array instrument and has been described elsewhere.^{95–97,102,103} The unique viewing angle of the linear array transducer allows for observation of the needle as it exits the biopsy channel and enables direction of the needle tip into the target lesion. A similar technique using a radial scanning echoendoscope has been reported; however, serious complications have been described via this technique, and it is not recommended.^94,103

EUS-guided FNA involves the insertion of the FNA catheter device through the accessory channel of the echoendoscope followed by deployment of the needle under EUS guidance into the lymph node to be sampled. The handle mechanism is secured to the accessory port, and if the instrument has an elevator, the elevator should be fully released into the down position to allow easy passage of the needle. The elevator can be used during the biopsy to direct the needle gently into the lesion. Doppler is used to identify surrounding vascular structures. The FNA needle is slowly advanced toward the target lesion. With certain needles, it helps if the stylet is withdrawn a few millimeters (2 to 3 mm), and the needle and the stylet are then directed into the target. When the needle has entered the lesion, the stylet is advanced (to clear the needle) and then removed. The endosonographer or assistant applies suction to the catheter system using a 5-mL or 10-mL Luer-Lok syringe. Suction is followed by “in-and-out” movements of the catheter after firmly locking the needle-catheter system to the appropriate depth so that the needle is not advanced beyond a desired depth. Typically, we make 7 to 10 gradual in-and-out movements within the lesion. Before removing the needle, the negative pressure is released slowly, the needle is removed from the lesion, and subsequently the needle system is unscrewed from the echoendoscope. It has been suggested to perform EUS-guided FNA of lymph nodes without the use of suction because suction may result in a bloody sample that may be more difficult for the cytopathologist to examine.¹⁰⁰

Preliminary cytology findings are obtained immediately during the FNA procedure by a cytopathologist or cytotechnologist present during the study. We recommend having a cytopathologist or cytotechnologist present during the EUS-guided FNA portion of the procedure because it can improve the efficiency of the technique. If a cytopathologist or cytotechnologist is unavailable, two to three passes should be taken by the endosonographer for lymph nodes (or liver metastases) and five to six passes should be taken for masses (similar to pancreatic masses) to ensure adequate cellularity in more than 90% of cases.^100,104 However, this approach is associated with a 10% reduction in definitive cytologic diagnoses, increased time and risk, and potentially the need for additional needles.¹⁰⁴

The FNA sample obtained is prepared for reviewing using Diff-Quik stain (HARLECO; EMD Chemicals, Inc, Gibbstown, NJ) applied to the slide containing the deposited specimen or fixed with ethanol. Additional passes are made until a positive cytology or adequate tissue sample is obtained. When lymphoma is suspected, added material is collected if possible and placed in a preservative solution (GIBCO RPMI Media 1640; Life Technologies, Carlsbad, CA) for subsequent flow cytometry and immunocytochemistry as indicated.^105,106 If an infection is suspected, a culture media can be used.

Other Malignant Mediastinal Disease

The most important indication for mediastinal imaging is the detection or staging (or both) of lung cancer. There are several reports of EUS-guided FNA in the cytologic diagnosis of mediastinal metastases from various extrathoracic malignancies in which EUS has played a pivotal role in detection or staging. These include metastatic pancreatic, esophageal, gastric, colon, laryngeal, germ cell, renal cell, breast, and ovarian cancers.^{76,77,79–83,107–110}

Most of the experience with EUS in patients with lymphoma has been in the setting of gastric lymphoma, although more recent studies support the use of EUS-FNA with flow cytometry for the diagnosis of mediastinal lymphoma as well.^80,111–113 In a study by Fritscher-Ravens and colleagues, 153 patients with mediastinal lymphadenopathy undergoing EUS-guided FNA, lymphadenopathy originating from the lung was present in greater than 80% of patients without a previous cancer diagnosis, whereas recurrence of extrathoracic sites was the major cause of mediastinal lymphadenopathy in patients with a previous malignancy.⁸⁰ Benign lesions and treatable second cancers were found in a significant minority of patients.

Devereaux and colleagues¹¹⁰ retrospectively reviewed a large, single-center experience with EUS-guided FNA for the diagnosis of mediastinal mass or lymphadenopathy in the absence of known pulmonary malignancy. In this report, 49 patients were analyzed; a malignant process was diagnosed in 22 of 49 (45%), and a benign process was found in 24 of 49 (49%). These included four patients with previously undiagnosed lung cancer, whereas metastatic breast carcinoma was the most frequent (6 of 22 [27%]) lesion. EUS-guided FNA was diagnostic in 46 of 49 (94%) patients. Catalano and coworkers¹⁰⁷ reported a multicenter study of 62 patients in which FNA results were classified as benign or infectious, malignant pulmonary, and malignant mediastinal (lymphoma, metastatic malignancy); EUS-guided FNA was diagnostic in 90% of cases. Panelli and associates¹¹⁵ reported a series of 33 patients with mediastinal masses, which represented 2.3% of 1447 upper EUS examinations over a 5-year period. EUS-guided FNA was performed in 25 of 33 (76%), of which 22 (67%) ultimately were determined to be malignant. Wiersema and coworkers⁸² reported a series of 82 patients with mediastinal lymphadenopathy, and EUS-guided FNA after other nonsurgical techniques failed to provide a diagnosis or could not be used. The sensitivity and specificity of EUS-guided FNA were 96% and 100%. In addition, a meta-analysis identified 76 studies, 32 of which described EUS-guided FNA, which confirm a high sensitivity and specificity for EUS-guided FNA in the diagnosis of mediastinal lymphadenopathy.¹¹⁶ These studies suggest that in the absence of accessible extrathoracic disease lesions or as an alternative, EUS-guided FNA is a useful technique for the cytodiagnosis of extrathoracic cancers that are metastatic to the mediastinum (Fig. 31.9).

Fig. 31.9 A 71-year-old woman with a history of breast cancer and melanoma was found to have mediastinal lymphadenopathy on chest computed tomography (CT). A, Radial endoscopic ultrasound (EUS) revealed a subcarinal 3.1 cm × 2.6 cm necrotic-appearing lymph node versus mass. B, Linear array imaging depicting fine needle aspiration (FNA) of this lesion. C, High-power magnification of hematoxylin and eosin stain on cell block shows metastatic pigmented melanoma. AO, aorta; AZ, azygos vein; LA, left atrium; LB, left bronchi; LV, left ventricle; PA, pulmonary artery; RB, right bronchi; TD, thoracic duct.

Nonmalignant Mediastinal Disease

Although commonly present in patients with suspected or known pulmonary malignancy, mediastinal lymph nodes are also present in patients with benign diseases such as histoplasmosis, tuberculosis, and sarcoidosis.^{80,110,117–121} In addition, benign cystic structures such as congenital foregut cysts account for approximately 20% of mediastinal masses.⁹³

Wiersema and coworkers¹¹⁷ described three patients with dysphagia from compression of the esophagus by mediastinal masses. EUS showed that the masses were enlarged lymph nodes with anechoic areas thought to represent caseating necrosis. The EUS-guided FNA finding of reactive lymphocytes along with a positive complement fixation titer was instrumental in making the diagnosis of mediastinal histoplasmosis. Savides and colleagues¹¹⁹ described 11 patients with dysphagia who had a midesophageal submucosal mass or stricture. EUS findings consisted of large, matted posterior mediastinal lymph nodes in all patients. The diagnosis of histoplasmosis was supported by the EUS finding of lymph node calcifications in seven of these patients, symptomatic improvement in response to antifungal medication in all seven patients who were treated, and a mean follow-up of 20.5 months in which none of the patients developed signs of a malignancy.

EUS has been reported to be an accurate and simple method for the diagnosis of sarcoidosis, a systemic granulomatous disease with a predilection for the lung and mediastinal lymph nodes.^{106,107,120–123} In most situations, the recommended procedure is a transbronchial biopsy, which has a diagnostic yield of 40% with one biopsy and 90% when four biopsy specimens are obtained.¹²² If the transbronchial approach is unsuccessful, more invasive diagnostic procedures such as mediastinoscopy or lung biopsy may be used.

Several more recent reports have described the utility of EUS-guided FNA in the diagnosis of sarcoidosis manifesting with mediastinal lymphadenopathy.^{106,107,120–122,124} Mishra and coworkers¹²⁰ described seven patients with mediastinal lymphadenopathy in which EUS helped confirm the diagnosis of sarcoidosis. Nodes were 1.8 to 6 cm in the long axis and were elongated and triangular and described as draping around the esophagus. In a retrospective review of 21 consecutive patients, Gress and colleagues¹²³ found EUS with FNA to have a sensitivity of 86% in diagnosing sarcoidosis in patients with mediastinal lymphadenopathy, but they failed to identify reliable EUS characteristics (shape, size, echogenicity, or homogenicity pattern) specific for the disease.

A study reporting the results of EUS-guided FNA evaluation in 19 patients with suspected sarcoidosis revealed enlarged mediastinal lymph nodes (mean size 2.4 cm) located subcarinally (n = 15), in the aortopulmonary window (n = 12), and in the lower posterior mediastinum (n = 5).¹⁰⁷ The nodes were described as isoechoic or hypoechoic, with “atypical” vessels in five cases. The aspirate obtained using EUS-guided FNA was adequate in all patients and contained blood in excess of normal in some, which was believed to be indicative of a high degree of vascularity. Cytology showed epithelioid cell granuloma formation, and cultures for mycobacteria were negative in all of the patients except one, in whom the final diagnosis was tuberculosis. The specificity and sensitivity of EUS-guided FNA in the diagnosis of sarcoidosis were 94% and 100%. Fritscher-Ravens and coworkers⁸⁰ found 2 patients with tuberculosis in 101 patients without a history of cancer who had EUS-guided FNA of mediastinal lymph nodes. This study highlights the need for acid-fast staining and culture to exclude tuberculosis in cases of noncaseating granulomas. In addition, there is potential for EUS-guided FNA in the cytologic diagnosis of intraabdominal and pancreatic sarcoidosis (Figs. 31.10 and 31.11).^{122,123,125,126}

Fig. 31.10 A, Radial imaging of large hypoechoic, oblong, and teardrop-shaped mediastinal lymph nodes (measuring up to 3.7 cm × 3.4 cm) in a patient with fever and elevated angiotensin-converting enzyme level. B, Fine needle aspiration (FNA) performed with linear array echoendoscope. C, High-power magnification of hematoxylin and eosin stain on cell block reveals a noncaseating epithelioid granuloma consistent with sarcoidosis. Special stains (acid-fast bacilli, Gomori methenamine silver) to rule out tuberculosis and fungal infections were negative. AO, aorta; LN, lymph node.

Fig. 31.11 Radial endoscopic ultrasound (EUS) from the body of the stomach in a patient with a history of sarcoidosis with peripancreatic lymphadenopathy that increased in size on serial transabdominal imaging. EUS revealed several hypoechoic lymph nodes. Fine needle aspiration (FNA) yielded tissue with prominent granulomatous inflammation thought to represent abdominal sarcoidosis.

Approximately 4% of regional lymph nodes of carcinomas have noncaseating epithelioid granulomas so that a presumptive diagnosis of sarcoidosis or another granulomatous disease should be made only after careful exclusion of malignancy and close follow-up.¹²⁷ Detectable mediastinal lymph nodes may also be present in normal subjects and are often found in patients undergoing EUS examinations for various indications (Fig. 31.12).^82,128 It has been postulated that detectable mediastinal lymph nodes in asymptomatic individuals may be related to prior histoplasmosis or other pulmonary infections.¹¹⁹ Devereaux and colleagues,¹¹⁰ in their retrospective study of 49 patients with mediastinal masses in the absence of known pulmonary malignancy, found a benign process in 24 of 49 (49%) including 8 patients with histoplasmosis, 1 patient with sarcoid, 2 patients with leiomyoma, 2 patients with duplication cyst, 1 patient with teratoma, and 10 patients with benign lymph node cytology on EUS-guided FNA.

Fig. 31.12 Radial imaging of benign-appearing mediastinal lymph nodes.

EUS is often useful in distinguishing cystic lesions from solid lesions in the mediastinum, whereas chest CT scan can have limited utility in providing this distinction.^91,129–134 Wildi and coworkers⁹¹ reported on a retrospective review of the results of EUS in 20 patients with suspected mediastinal cysts. The features used to classify cysts were as follows: Benign simple cysts appear as anechoic or hypoechoic smooth, spherical structures with well-defined thin walls; esophageal duplication cysts are adherent to the esophagus, whereas cysts originating from the airways are designated as bronchogenic cysts. Cysts that do not fall into either category are termed nonspecific duplication cysts. A layered wall structure supports the diagnosis of duplication cyst but is not mandatory. Simple cysts include mesothelial cysts, lymphogenous cysts, and thoracic duct cysts. Simple cysts do not have a layered wall and do not have a connection to the airways or esophagus and are termed nonspecific simple cysts. When solid tissue is seen within the fluid, the cysts are considered complex (e.g., benign cystic teratoma, thymic cyst), and the diagnosis of a benign simple cyst is excluded.

In 19 of 20 patients reported by Wildi and coworkers,⁹¹ definite diagnosis of a mediastinal cyst was established by EUS (12 anechoic, 6 hypoechoic, 1 anechoic with small echoic foci). In only 4 of 18 cases was CT (17 cases) or MRI (1 case) diagnostic of a cyst. In three cases with mixed echo features, EUS-guided FNA was performed with administration of prophylactic antibiotics. In a fourth case, without prior prophylactic administration of an antibiotic, FNA was performed in a solid-appearing duplication cyst misdiagnosed by EUS as extensive lymphadenopathy. Mediastinitis subsequently developed requiring thoracotomy, in which an infected bronchogenic cyst was diagnosed. The authors concluded that aspiration of cysts should be avoided in lesions with clearly anechoic features because of the risk of infection, whereas FNA should be considered for hypoechoic lesions (when a cyst cannot be clearly distinguished from a solid tumor), but prophylactic antibiotics should be administered (Fig. 31.13).

Fig. 31.13 A, Chest computed tomography (CT) shows an ill-defined soft tissue density adjacent to the midesophagus. B, Linear array imaging of this lesion reveals a paraesophageal duplication cyst.

Adrenal and Renal Lesions

EUS can provide early excellent images of the left adrenal gland. The right adrenal gland is also accessible by EUS, and its routine evaluation may be feasible, although it is more difficult to visualize than the left adrenal gland, and the procedure is not routinely performed.¹³⁵ The left adrenal gland is more difficult to view than the right gland when imaging with transabdominal ultrasound.^136–138

When imaging the left adrenal gland, the echoendoscope is advanced into the proximal stomach, and the aorta is identified just below the GE junction. The splenic vein is imaged by advancing the transducer forward with a clockwise rotation. Following the splenic vein laterally, the splenic hilum is found by further clockwise rotation and slight withdrawal. The left kidney is imaged by advancing the scope from the splenic hilum with a slight counterclockwise rotation. The left adrenal gland lies just below the splenic vein, between the left kidney (superior and medial to the kidney) and the aorta. In a study by Chang and colleagues,¹³⁸ the average long-axis dimension of the adrenal gland was 2.5 cm, and the short-axis dimension was 0.8 cm. The adrenal gland as imaged on EUS is homogeneous and hypoechoic with two basic morphologic types: seagull shape and elliptical shape. Occasionally, the adrenal gland can appear as both shapes in the same patient with a slight change in the orientation of the EUS probe tip.¹³⁸ In some patients, the central region of the gland may appear more echogenic than the peripheral region (Fig. 31.14).

Fig. 31.14 Radial imaging from the body of the stomach showing the left adrenal gland, aorta (AO), splenic vein (SV), left (LT) kidney, and body of the pancreas (PANBODY).

Incidental benign adrenal lesions, so-called adrenal incidentalomas, are commonly found on CT scans performed for various indications. Unless unequivocally benign, biopsy of these lesions should be performed in certain scenarios. CT scans performed in the staging work-up of lung cancer reveal that more than 16% of patients have adrenal masses on screening examination.^138–143 Metastasis to the adrenal glands as the cause of isolated mass lesions occurs in 32% to 93% of cases of NSCLC as determined by FNA cytology.^141,144 In autopsy series of NSCLC, adrenal metastases are found in 59% of cases.^145,146

EUS-guided FNA may provide an alternative to percutaneous aspiration technology in the evaluation of adrenal lesions. EUS-guided biopsy of an adrenal mass has been reported in a patient in whom CT-guided FNA was unsuccessful.¹⁴⁷ Chang and associates¹⁴⁷ reported the identification of the left adrenal gland in 97% of 31 consecutive patients undergoing EUS for known pulmonary or GI malignancies. In one patient with a history of lobectomy for lung cancer, staged as T1N0, a follow-up CT scan showed interval enlargement of an adrenal mass from 2.5 cm to 4 cm. A previous CT-guided FNA was negative for malignancy. An EUS-guided FNA of the left adrenal gland was performed and revealed metastatic disease. A more recent case series also suggests that the right adrenal gland may be more accessible by EUS-guided FNA than previously believed.¹³⁵ Given the clinical impact of an adrenal metastasis, routine assessment of the left and possibly right adrenal glands in patients with lung cancer is recommended during the EUS evaluation.¹⁴⁷

EUS of the right and left kidneys is possible because of the immediate approximation between the GI lumen and the kidneys. The right kidney can be imaged by placing the transducer in the second portion of the duodenum and rotating laterally. The left kidney can be imaged from the body of the stomach, posterior to the spleen, as described previously. The left kidney often is easier to show than the right kidney. The kidneys have a hyperechoic central medulla, a hypoechoic outer cortex, and a thin echogenic capsule (Fig. 31.15).

Fig. 31.15 A, Radial imaging from the duodenum shows excellent images of the right kidney in this patient with malrotation of the right kidney. The liver is seen in the upper portion of the image. B, Radial imaging from the body of the stomach shows the left (LT) kidney, spleen, body and tail of the pancreas (closest to the transducer) and above the splenic vein. The left renal vein is seen exiting the kidney.

Approximately 85% of renal masses detected on CT are renal cell carcinomas, and 15% of CT-detected renal masses are benign lesions.^148,149 Biopsy of malignant-appearing masses that are resectable should not be routinely performed. Biopsy of a solitary renal mass is generally accepted in cases with a known primary extrarenal malignancy when the presence of a metastasis would alter management.^148,150 Biopsy specimens of renal masses have traditionally been obtained under either transabdominal ultrasound or CT guidance with a sensitivity of 62% to 100% and a specificity of 0% to 100% in the diagnosis of renal cell carcinoma.^114,148 No data currently exist regarding the frequency with which renal masses are identified during upper EUS examinations. A few case reports exist showing the possibility of making a diagnosis of renal cell carcinoma using EUS-guided FNA^148,151; however further experience is required before the establishment of EUS-guided FNA as a modality for performing renal biopsy.

Ascites and Pleural Fluid

The identification of malignant pleural effusion or malignant ascites is diagnostic of advanced disease in various malignancies. EUS seems to be more sensitive than CT in the detection of small amounts of ascites and pleural fluid. Drainage of pleural fluid or ascites at the time of EUS is possible and can be helpful if positive for malignancy. The technique of EUS-guided FNA of ascites or pleural fluid is similar to the technique applied to other lesions. Seeding of malignant cells into the fluid through the GI tract is a concern. The site of the needle penetration in the GI lumen must not be involved with tumor (Fig. 31.16).

Fig. 31.16 A, Radial imaging of trace ascites in a patient with pancreatic cancer. The pancreatic mass is seen below the ascites. B, Ascites in a patient with linitis plastica. C, Pleural effusion (PLEF) seen adjacent to the right lung (RL). AO, aorta.

Chang and associates¹⁴⁷ first reported the detection of malignant fluid via EUS-guided FNA of pleural effusion and ascites in patients with gastric cancer. In a larger retrospective study, these same investigators reported the utility of EUS for the detection of ascites and EUS-guided FNA in 571 consecutive patients who underwent upper EUS for various indications.¹⁵² EUS detected ascites in 85 (15%) patients, whereas CT detected ascites in 14 (18%) of the 79 patients who underwent CT scanning before EUS. Of 85 patients, 31 underwent EUS-guided FNA paracentesis, and malignant ascites was diagnosed in 5 of these patients. More recently, investigators have been looking at whether detection of low-volume ascites by EUS is a good predictor of outcomes in esophageal cancer.^139,153 These studies have shown that patients with ascites detected only by EUS examination have a shorter survival than patients without low-volume ascites. However, patients with ascites whose tumors were still deemed surgically resectable had the same survival rate as patients without ascites. These findings have been supported by similar studies that have described the clinical significance of peritoneal fluid detected by EUS.^154,155

Liver Lesions

EUS provides very good imaging of the left lobe of the liver and a significant portion of the right lobe of the liver. The left lobe and hilum of the liver are examined from the gastric body and fundus. The tip of the echoendoscope is placed in the gastric antrum; then, slowly withdrawing the echoendoscope, the tip is deflected up and rightward. When the liver comes into view, the instrument is rotated to evaluate portions of the liver. The right lobe of the liver is best imaged from the duodenum but can also be seen from the antrum. Liver lesions near the second or third portion of the duodenum, peripheral lesions near the dome of the diaphragm, and lesions in the inferior portion of the right lobe of the liver can be difficult to visualize (see Figs. 31.2 and 31.15).¹⁵⁶

CT-guided and ultrasound-guided FNA of liver lesions have been reported to have sensitivities of 83% to 93% for the detection of malignant disease.^{138,140–143} Although EUS has not traditionally been used in evaluation of the liver, early experience suggests that EUS-guided FNA is comparable to CT-guided FNA in terms of safety and diagnostic utility for hepatic lesions.^156–161 Nguyen and associates¹⁵⁶ conducted a prospective study in which 574 consecutive patients with a history or suspicion of GI or pulmonary tumor who were undergoing upper EUS examinations underwent EUS evaluation of the liver. They found small focal liver lesions that were undetected with conventional CT. Of patients, 14 (2.4%) were found to have focal liver lesions (five right lobe, nine left lobe) and underwent EUS-guided FNA. The median largest diameter of the liver lesions was 1.1 cm (range 0.8 to 5.2 cm), and the mean number of passes per lesion was 2.0 (range 1 to 5 passes). Of the 15 liver lesions sampled via EUS-guided FNA, 15 were malignant and 1 was benign. Before EUS, CT depicted liver lesions in only 3 of 14 (21%) patients; in most patients, CT was performed within 2 months of the EUS procedure. In seven patients, the initial diagnosis of cancer was made by means of EUS-guided FNA of the liver. There were no immediate or late complications.

Rarely, percutaneous FNA of the liver has been associated with tumor seeding, intrahepatic hematoma, and hemorrhage.^162–166 As postulated by Nguyen and coworkers,¹⁵⁶ EUS-guided FNA has the possible advantage over the percutaneous route of shorter insertion length of the needle if the liver lesion is deep to the skin surface. With EUS-guided FNA, there is continuous visualization of the needle tip, which helps to minimize risk for bleeding when the procedure is performed in conjunction with color flow and Doppler ultrasound. tenBerge and colleagues¹⁶¹ reported a multicenter study of 167 cases of EUS-guided FNA of the liver. Complications were reported in six (4%) cases, including death in one patient with an occluding biliary stent and biliary sepsis, bleeding (one case), fever (two cases), and pain (two cases). In 23 of 26 patients, EUS-guided FNA helped diagnose malignancy after nondiagnostic FNA with transabdominal ultrasound guidance. EUS was able to localize an unrecognized primary tumor in 17 of 33 (52%) cases after CT showed only liver metastases. This study highlighted the fact that adequate biliary drainage is recommended in the setting of cholangitis before or coincident with the FNA procedure. EUS-guided FNA of liver lesions seems to be safe and effective and may become a more useful diagnostic method for liver lesions.

Miscellaneous

The close proximity of the intestinal tract to abdominal organs raises the possibility of EUS-guided FNA of idiopathic abdominal masses. Catalano and coworkers¹⁶⁷ retrospectively evaluated the diagnostic accuracy of EUS-guided FNA of abdominal masses of unknown cause and its impact on subsequent evaluation. From five tertiary referral centers, 34 patients with idiopathic abdominal masses underwent EUS-guided FNA after evaluation including CT or transabdominal ultrasound, or both. CT showed an intraabdominal mass in all patients. Four patients had a history of intraabdominal cancer (two cervical, one ovarian, one colon), but these cancers were considered to be in remission. A final diagnosis for the mass lesions was established in all patients by various methods, including EUS-guided FNA, surgery, autopsy, or long-term follow-up. Abdominal masses were classified into three categories: infectious, benign or inflammatory, and malignant. EUS-guided FNA established a tissue diagnosis in 29 of 34 (85%) patients: infectious, 80% including abscess and infected pseudocyst; benign or inflammatory, 67% including hematoma or postsurgical inflammatory mass, leiomyoma, and sarcoidosis; and malignant, 91% including sarcoma, lymphoma, hepatoma, adenocarcinoma of unknown primary, ovarian cancer, transitional bladder carcinoma, uterine or cervical cancer, recurrent colon cancer, neuroendocrine tumor, paraganglionoma, metastatic lung cancer, and prostate cancer. EUS-guided FNA was instrumental in directing subsequent evaluation in 29 (85%) patients and therapy in 26 (77%). The number of fine needle passes needed for adequate tissue sampling was lower for nonmalignant (2.2 to 3.2 passes) versus malignant diseases (4.6 passes). A perirectal abscess developed in one patient and was treated successfully with antibiotics.

Cases using EUS-guided FNA to diagnose a schwannoma of the mediastinum¹⁶⁸ and a retroperitoneal neurilemoma have been described.¹⁶⁹ In addition, studies by Erickson and Tretjak¹⁷⁰ and Anand and colleagues¹⁷¹ have helped show that EUS-guided FNA is an effective method with a high sensitivity and specificity for diagnosing and altering patient management of nonpancreatic lesions adjacent to the GI tract.

Accessory spleen may be a potential cause of misinterpretation on EUS. Barawi and colleagues¹⁷² described the EUS features of accessory spleen in 10 (8 accessory spleen, 2 lobulated spleen) patients. The mean size of these lesions was 2.7 cm × 3.1 cm. Nine accessory spleens were round, and one was oval. All were located inferolateral to the pancreatic tail and medial to the spleen. All of these lesions had a sharp and regular outer margin and homogeneous echo texture; four were hypoechoic, and six were hyperechoic. CT scan may be helpful in confirming the presence of lobulated spleen and accessory spleen (Fig. 31.17).

Fig. 31.17 Radial imaging from the stomach of an accessory spleen.

Fritscher-Ravens and associates¹⁷³ described EUS-guided FNA of splenic lesions in 12 patients when other modalities were inconclusive (n = 5), not attempted because of small size (0.9 to 1.4 cm; n = 4), or considered dangerous (adjacent to the splenic hilum or located peripherally; n = 3). The lesions ranged in size from 0.8 to 4.2 cm (median 1.4 cm). A positive diagnosis was made in 10 of 12 patients (83%); cytology was inadequate in 1 patient. Bacteriology was positive for Staphylococcus aureus and Serratia in one patient each and for Mycobacterium tuberculosis in two patients. Diagnoses included lymphoma, sarcoidosis, abscesses, tuberculosis, metastatic colon cancer, and infarction (in one patient). One patient experienced pain after the procedure, but no hematoma was shown on subsequent ultrasound examination. Since this study, other studies have been performed supporting the possibility that EUS-guided FNA of splenic masses is feasible and safe.^174,175

Complications

EUS-guided FNA is a relatively safe procedure compared with CT-guided FNA, bronchoscopy with transbronchial FNA, mediastinoscopy, or open or exploratory procedures. Generally, when complications occur, these are usually mild and self-limited. In reports and more recent prospective studies that have addressed complications of EUS-guided FNA, rare complications included endoscope-induced perforations, febrile episodes (after FNA of pancreatic cystic lesions), hemorrhage, pancreatitis, and pneumoperitoneum; false-positive diagnoses have been described.^{79,89,92,93,158,176–180} As alluded to previously, the role of prophylactic antibiotics for EUS-guided FNA is unclear. The general practice has been to administer antibiotics to any patient undergoing FNA of cystic pancreatic or perirectal lesions. Barawi and colleagues⁸⁶ studied 108 consecutive EUS-guided FNA cases that did not show bacteremia at 30 minutes and 60 minutes after the procedure. However, the study by Van de Mierop and colleagues⁹³ revealed a 19% incidence of bacteremia with EUS-guided FNA of solid lesions.

Technique for Performing Endoscopic Ultrasound–Guided Celiac Plexus Block and Celiac Plexus Neurolysis

This section focuses on endoscopic methods of EUS-guided CPB and CPN. Patients with inoperable pancreatic cancer and pain requiring narcotic analgesics are potential candidates for CPN. Selection of patients with pain related to chronic pancreatitis for CPB is less clear. Patients with pain refractory to high doses of narcotics may be appropriate candidates, although the response may be minimal.

The celiac artery is readily visualized with a curvilinear array EUS scope and provides the important landmark structure when performing EUS-guided CPB and CPN. For practical purposes, the celiac ganglia is located at the origin of the celiac artery, although its exact location has been described anywhere from 1 cm to 9 mm inferior to the artery takeoff (the right ganglion is most commonly 6 mm inferior and the left ganglion is most commonly 9 mm inferior to the celiac artery origin).^195,197 Although the celiac ganglia themselves can be visualized in some cases, the celiac axis is more routinely identified by its relative position to the artery. The proximity of the celiac ganglia to the posterior gastric wall ensures an accurate passage of the needle into the ganglia, minimizing the risk of complications and potentially increasing the effectiveness.

The patient is hydrated before the procedure with intravenous saline (500 to 1000 mL) and is placed in the left lateral decubitus position, and sedation is administered. Blood pressure, pulse oximetry, and electrocardiogram are continuously monitored. The linear array echoendoscope is advanced to just below the GE junction. A sagittal view of the aorta is obtained through the posterior gastric wall. The aorta is traced to the celiac trunk, the first large vessel emerging off the aorta, and the second branch is usually easily identified as the superior mesenteric artery. Identifying both the celiac artery and the superior mesenteric artery helps to confirm the correct location. Color flow Doppler should be used to exclude any intervening vessels.

After the stylet is removed from the 22-gauge FNA needle, the entire system is flushed with normal saline to remove any air because this can interfere with imaging. Using real-time imaging, the sterile FNA needle is inserted immediately lateral and anterior to the aorta at the level of the celiac trunk via a transgastric approach. A small amount (2 mL) of 0.9% saline is injected to clear the needle. An assistant aspirates a 10-mL syringe filled with 0.9% saline for approximately 10 seconds to confirm that the needle is not within any of the regional blood vessels.

Two techniques are available: one in which the injection is performed by rotating to each side of the celiac trunk and one in which the entire injection is performed just anterior and cranial to the celiac artery takeoff.^193,195 For CPB, 10 mL of preservative-free bupivacaine (0.25%; Abbott Laboratories, Abbott Park, IL) and 1 mL of triamcinolone (40 mg; Fujisawa USA, Deerfield, IL) are injected on both sides of the celiac trunk. The aspiration test is repeated before each steroid injection. A 3-mL saline flush is performed before needle withdrawal on each side. For CPN, 10 mL of bupivacaine (0.25%) is injected followed by 10 mL of dehydrated 98% absolute alcohol. Before alcohol injection, the 10-second aspiration test is repeated. The needle is flushed with 3 mL of saline before withdrawal of the needle. The procedure is repeated on the opposite side of the aorta. With alcohol injection, an echo-dense cloud is typically seen, but this is not usually seen with steroid injection.

For the alternative approach, a single-site injection at the base of the celiac artery takeoff is performed with the entire amount of the injectant—20 mL of bupivacaine (0.25%) and 20 mL of dehydrated alcohol in CPN and 20 mL of bupivacaine (0.25%) and 80 mg (2 mL) of triamcinolone in CPB. There are no studies comparing the two techniques, but it is believed that they have similar results. Anatomic variations may determine which technique is used.

The examination, performed on an outpatient basis, is usually completed in 30 minutes. Recovery time is usually 2 hours. Before discharge, orthostatic blood pressure changes should be checked, and patients should be counseled regarding potential complications (see video on expertconsult.com).

Complications

CPB and CPN are generally effective, safe, and well-tolerated procedures. The three most common complications are transient hypotension (20% to 40%), transient diarrhea (4% to 38%), and transient increase in pain (9%), which are expected in CPB performed via any route.^195,198,209 Interruption of the plexus can result in a sympathetic blockade.²¹⁰ Clinical manifestations of sympathetic blockade can include diarrhea and hypotension resulting from a relative unopposed visceral parasympathetic activity. Mesenteric vasodilation accounts for the hypotension, which resolves in approximately 2 days. Diarrhea and increase in baseline pain are also usually limited to 2 days. Less common complications include unilateral paresis or paraplegia, pneumothorax, loss of sphincter function, retroperitoneal bleeding, renal puncture, and prolonged gastroparesis.^{193,195,198,199,209} In addition, cephalic spread of the neurolytic agent may result in involvement of the cardiac nerves and plexus.²¹¹ Although not unique to EUS-guided CPN, EUS may decrease the incidence of complications because the needle does not traverse the paraspinal region or somatic nerves or traverse the diaphragm and pleural space.^180,193,195 Another benefit with EUS-guided CPN is the ability to perform the block as part of a single procedure that may include tumor staging and FNA.²¹² Infectious complications are uncommon but potentially serious. In a series of 90 patients, only 1 patient developed an infectious complication (peripancreatic abscess), which resolved with a 2-week course of antibiotics.²⁰⁸ The authors reasoned that there may have been a predisposition to infection owing to gastroduodenal colonization with bacteria because the patient was taking a proton pump inhibitor. They suggested that prophylactic antibiotics should be considered in patients who are receiving acid suppression. The bactericidal nature of ethanol seems to minimize this risk for infection, and some experts do not routinely use antibiotics in this setting, regardless of concurrent acid suppression.¹⁹³