Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract

Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract Peter Vilmann, MD S¢ren Hancke, MD, PhD Finn Wilkens Henriksen, MD, PhD Grete Krag Jacobsen, MD, PhD I n t e r e s t in endoscopic u l t r a s o n o g r a p h y (EUS) has increased during recent years. Several studies have shown t h a t the use of high-frequency ultrasonic transducers built into the tip of a flexible endoscope m a k e s it possible to depict lesions in a n d a r o u n d the gastrointestinal t r a c t accurately. TM However, it is not possible to differentiate b e t w e e n m a l i g n a n t and benign lesions using EUS. 512 In an a t t e m p t to solve this problem, a new t e c h n i q u e for E U S - g u i d e d fine-needle a s p i r a t i o n (FNA) has b e e n developed. T h e aim of this s t u d y is to p r e s e n t our experience with E U S - g u i d e d F N A biopsy of lesions in and a r o u n d the u p p e r gastrointestinal tract.

Figure 1. The

curved-array ultrasonic transducer is mounted at the tip of the endoscope behind the optic lens, enabling a needle to be introduced into the sector-shaped soundfield. The needle can therefore be visualized both through the optics and on the ultrasonographic image.

METHODS AND PATIENTS Endoscope The Pentax/Hitachi FG-32UA ultrasonic endoscope (Pentax Precision Instrument Corp., Orangeburg, N.Y.) is a 60 ° oblique-forward-viewing fiberoptic gastroscope with a curved-array ultrasonic transducer mounted in front of the optic lens (Fig. 1). The transducer is 20 mm long and 12 mm wide. The scanning plane is in the long axis of the endoscope. The transducer frequency can be adjusted to either 5 MHz or 7.5 MHz. The lateral and axial resolution is 0.8 mm at 7.5 MHz, and the penetration depth is 6 cm at 5 MHz and 5 cm at 7.5 MHz. A biopsy channel, 2 mm in diameter, ends close to the optic lens, enabling conventional endoscopic instrumentation. Because of the sector-shaped soundfield and the direction of the scanning plane, it is possible to visualize ultrasonographically a needle that is inserted through the biopsy channel. When a needle is introduced into the soundfield, the needle and its tip can be seen as strong echoes on the ultrasonoReceived November 5, 1993. For revision January 17, 1994. Accepted July 27, 1994. From the Department of Surgical Gastroenterology, Ultrasonic Laboratory, and Department of Pathology, Gentofte University Hospital, Denmark. Reprint requests: Peter Vilmann, MD, Dept. of Surgical Gastroenterology C, Rigshospitalet, 2100 Copenhagen O, Denmark. 0016-5107/95/4103-023053.00 + 0 GASTROINTESTINAL ENDOSCOPY Copyright © 1995 by the American Society for Gastrointestinal Endoscopy

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Figure 2. For EUS-guided FNA biopsy, a 160-cm-long steel needle, 0.7 mm in outer diameter, is used with a stylet and Teflon catheter.

graphic image, so that movements of the needle can be monitored. Simultaneously, part of the needle can be seen through the optic lens. The gastroscope itself has a diameter of 10.8 mm and a total length of 160 cm. A balloon can be mounted around the transducer. The instrument, which is connected to a Hitachi ultrasonic scanner (EUB-515), also allows for duplex examination, color-flow imaging, and spectral analysis for measurement of flow velocity.

Needle The steel needle (GIP Medizin Technik GMBH, Grassau, Germany), which was developed after 2 years of experience with several other prototype needles, is 160 cm long and 0.7 mm in outer diameter (Fig. 2). The needle is placed in a 140cm-long, 5F Teflon catheter to protect the biopsy channel during introduction. A styler positioned 2 mm outside the tip of the needle prevents it from penetrating the Teflon catheter. When the catheter with the needle is inserted into the endoscope, its end is just outside the distal end of the biopsy channel. The needle can be advanced up to 12 cm beyond the catheter. VOLUME 41, NO. 3, 1995

Examination procedure EUS is performed using midazolam for conscious sedation with the patient in a left lateral decubitus position. In esophageal examinations, the transducer is placed directly on the mucosa or on the surface of a lesion. In patients with gastric disease, either direct contact between mucosa and transducer or instillation of water in the stomach is used. The head of the pancreas and the papilla are visualized from the second part of the duodenum during direct contact of the transducer against the duodenal wall. The body and tail of the pancreas are visualized from the stomach, and most often direct contact of the transducer with the mucosa is sufficient. When biopsy is to be performed, the balloon around the transducer is not filled with water because it is thought to interfere with the needle puncture.

Biopsy technique In most cases, an assistant is responsible for introduction of the needle and aspiration of material. This is necessary because the endoscopist has to maintain the transducer in contact with the gastrointestinal wall during the needle puncture. The detailed steps of the biopsy procedure are as follows: 1. The needle with the stylet placed within the Teflon catheter is introduced through the biopsy channel of the endoscope. 2. The needle is advanced 1 cm beyond the Teflon catheter so that the reflections of the needle tip are seen ultrasonically. 3. The stylet is withdrawn a few millimeters. 4. The needle with the stylet is pushed into the lesion under ultrasonic guidance. 5. The stylet is removed. 6. Vacuum is applied to the needle by means of a 20-mL syringe. 7. The needle is further advanced into the lesion and moved back and forth under ultrasonic guidance. 8. The vacuum is equilibrated while the tip of the needle is within the lesion. 9. The entire needle with the Teflon catheter is removed, and the aspirated material is expelled and smeared on glass slides. 10. The material is air-dried and stained for cytologic examination (May-Grfinwald-Giemsa). In cases of suspected spread from primary malignant lymphomas, special cytologic staining is used. The biopsy procedure is repeated until sufficient material has been aspirated as judged by the macroscopic appearance. The cytologic analysis is performed the following day. Antibiotics are not used routinely.

Patients EUS with guided biopsy was performed in 33 consecutive patients suspected of having malignancy in the upper gastrointestinal tract. Half of the patients with suspected lesions of the esophagus (10) and the stomach (12) were referred for primary diagnosis, whereas the other half, with a known primary cancer diagnosis, were referred for staging. Two of the patients in the group with pancreatic lesions had a previously diagnosed malignant tumor and were referred V O L U M E 41, NO. 3, 1995

for staging, whereas 8 patients were referred for primary diagnosis because of clinically suspected pancreatic malignancy. One patient was referred for primary diagnosis of a solid lesion in the mediastinum demonstrated by CT. Mean age was 64 years (range, 34 to 80 years). In these 33 patients, 44 lesions were outlined by EUS. In most cases, 2 to 3 specimens were taken from each lesion (range, I to 4; average, 2).

RESULTS Results are s u m m a r i z e d in T a b l e s I to 3. S p e c i m e n s were t a k e n f r o m a t o t a l of 44 lesions, as 11 p a t i e n t s h a d s p e c i m e n s t a k e n f r o m 2 lesions. T h r e e p a n c r e a t i c lesions of 1i 2.5, a n d 3 cm were not d e m o n s t r a t e d b y either C T or external ultrasonographic examination. T h i r t y - s i x solid lesions p r o v e d to be m a l i g n a n t either by autopsy, operation, conventional forceps biopsy, or follow-up. I n 31 of these cases, E U S - g u i d e d biopsy revealed m a l i g n a n t cells, i.e., cells a s p i r a t e d were sufficient for analysis. A p a n c r e a t i c cyst a d e n o m a was diagnosed in 1 p a t i e n t b y F N A biopsy, b u t subseq u e n t o p e r a t i o n revealed a m a l i g n a n t p a n c r e a t i c lesion. In 4 cases, the m a t e r i a l a s p i r a t e d was not sufficient for a cytologic diagnosis, i.e., the aspirate did n o t contain cells for analysis. E x a m p l e s of m a l i g n a n t lesions are d e m o n s t r a t e d in Figures 3 to 8. T h e needle has b e e n i n t r o d u c e d obliquely into the s e c t o r - s h a p e d soundfield, a n d strong echoes f r o m the needle are seen in the solid lesions. E i g h t of the 44 lesions were benign, as proved by rep e a t e d endoscopy with biopsy, clinical follow-up for m o r e t h a n 12 m o n t h s , or both. A p a n c r e a t i c cyst was p r o v e d benign by surgery. In 1 p a t i e n t with chronic l y m p h a t i c leukemia, cytology showed an a b u n d a n c e of small a n d m a t u r e l y m p h o c y t e s ; these were sufficient for a conclusive diagnosis b y the cytopathologist. E U S - g u i d e d cytology was conclusive for benign diagnosis (sufficient aspirate) in 5 cases; in 3 cases, the m a t e r i a l a s p i r a t e d was acellular, i.e., insufficient for cytology. As seen in T a b l e 2, the predictive value of the positive cytologic diagnosis is 31/31 or 100% (89% to 100% ), a n d the predictive value of the negative cytologic diagnosis is 5/6 or 83% (36% to 100%), with a 95% confidence interval. T h e s e n u m b e r s do not include t h e relatively high rate of cases with insufficient m a t e r i a l for cytologic diagnosis, 7/44 or 15 % (7 % to 30%). No complications were related to the biopsy procedures.

DISCUSSION E U S allows for detailed s t u d y of the gastrointestinal wall and of organs a n d s t r u c t u r e s adjacent to the gast r o i n t e s t i n a l tract. D e s p i t e significant progress in E U S imaging during the p a s t 10 years, the clinical i m p a c t of E U S findings has until now been limited. T h i s m a y reflect the difficulties e n c o u n t e r e d in using E U S to differentiate m a l i g n a n t f r o m benign lesions. W i t h a GASTROINTESTINAL ENDOSCOPY

231

Table 1. Results of EUS-guided FNA biopsy of 44 lesions Malignant Benign lesions lesions Location Diagnosis (n)

Verification

(n)

31,

Esophagus (8) Stomach (5) Pancreas (4) Common bile duct (1) Lymph node (12) Mediastinum (1)

1t

Pancreas

45

Stomach (1) Pancreas (2) Esophagus (1) 5~

Esophagitis (1) Gastritis (1) Normal lymph node (2) Pancreatic pseudocyst (1)

Biopsy and follow-up Biopsy and follow-up Follow-up Operation

35

Pancreatitis (1) Gastric ulcer (2)

Follow-up Biopsy and follow-up

*Conclusive cancer diagnosis. tConclusive noncancer diagnosis. ~Insufficient material aspirated.

Table 2. Predictive value of EUS-guided FNA biopsy EUS diagnosis Final diagnosis Insufficient + material + 31 1 4 -

0

5

3

31

6

7

mechanically rotating 360 ° scanner, EUS-guided biopsy is difficult because the ultrasonic scanning plane is unsuitable for monitoring the needle. Several studies have shown that endoscopic FNA biopsy is accurate and in many cases superior to conventional histologic biopsy in the diagnosis of malignant gastrointestinal lesions. 13-17 Also, very few false-positive diagnoses are made with FNA cytology. The results of the present study using a new-generation ultrasound endoscope with curved linear-array transducer show that it is possible to aspirate material for cytologic examination from various small lesions within or outside the gastrointestinal wall. EUSguided biopsy was performed in 44 lesions during the study, and no complications related to the puncture procedure were encountered. With this technique, material could be aspirated for cytology even from small lymph nodes in the mediastinum, around the 232 G A S T R O I N T E S T I N A L E N D O S C O P Y

celiac axis, in the smaller omentum, along the left gastric artery, and in the gastroduodenal ligament. Several of the lesions punctured were not visible by external ultrasonography or CT. In most cases, the aspiration biopsies were performed by an assistant because the endoscopist had to maintain the transducer in contact with the gastrointestinal walt during the procedure. Introduction of the needle into a lesion is most easily performed while the endoscope is in a straight position, as is the case in the esophagus. However, puncture is also possible with the scope in a curved position, as when placed into the second part of the duodenum. In cases in which the tip of the endoscope is flexed maximally or the endoscope is looped, the instrument should be deflected until passage of the needle through the scope is possible. It is important not to withdraw the stylet more than a few millimeters before puncture in order to prevent water or mucus from being aspirated into the needle and to keep tissue plugs from the superficial layers from becoming stuck inside the needle. Before removal of the needle, it is mandatory to equilibrate the vacuum completely. If this is not done, water or mucus will inevitably be sucked into the needle when removed, thereby destroying the aspirated specimen, possibly because of osmotic destruction of the cells. This was our experience during aspirations with early, prototype needles. These factors partly exVOLUME 41, NO. 3, 1995

Figure 3. Periampullary cancer, 3 cm in diameter. The transducer is placed in the second part of the duodenum. The needle is visualized in the echo-poor lesion. Arrows, needle echoes.

Figure 4. Malignant cyst, 2.5 cm in diameter, in the tail of the pancreas. The needle traverses the posterior gastric wall before entering the cyst. Arrows, needle echoes.

plain the relatively high percentage of cases with insufficient material aspirated (Tables 1 and 2). If a lymph node is located behind a solid mass lesion in the wall and if a needle puncture of both is planned, the lymph node should be targeted first. When the needle traverses the larger tumor, the stylet should be in place within the needle in order to prevent cells from the tumor from entering the needle. A tendency to lose ultrasonic contact with the needle, particularly when hard lesions are punctured, has been noted. This, however, is not a big problem, because contact is easily re-established by adjustment of the transducer. The importance of maintaining a steady position of the transducer in relation to the lesion to be punctured should be stressed. When the needle is introduced V O L U M E 41, NO. 3, 1995

Figure 5. Malignant lymph node, 1.5 cm in diameter, located at the celiac axis. The transducer is placed on the posterior wall of the stomach. Arrows, needle echoes; In, lymph node; A, aorta.

Figure 6. A malignant lymph node, 0.7 cm in diameter, located between the cardia and the liver. The needle traverses the esophageal wall in the upper left side of the image. Arrows, lymph node; VC, vena cava; L, liver. Strong reflections from the needle are visible.

through the gastrointestinal wall, it seems relatively easy to hit the target because of the short distance involved as compared with conventional ultrasonically guided percutaneous puncture, in which the distance to the target may be very long. However, it may be difficult to keep the transducer in contact with the gastrointestinal wall because the wall and surrounding structures tend to move and the transducer tends to be displaced when needle puncture is performed. This occurs especially often when the transducer is placed in a water-filled stomach without contact with the wall. Although this study has demonstrated that EUSguided FNA biopsy is useful in the differentiation beGASTROINTESTINAL ENDOSCOPY

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Figure 7. Malignant lymph node, 1 cm in diameter, located outside a solid lesion of the stomach wall. The needle traverses the stomach wall before it enters the lymph node. Arrows, needle echoes; In, lymph node.

Figure 8. Malignant lymph nodes, 1.5 cm in diameter, located in the mediastinum between the esophagus and the pulmonary artery. Arrows, needle echoes;/n, lymph node; p, pulmonary artery.

Table 3. Results of EUS-guided FNA biopsy of lymph nodes in 14 patients Diagnosis of primary lesion

Location of lymph node

Diameter (cm)

Biopsy conclusive

Gastric cancer Esophageal cancer Pancreatic cancer Esophageal cancer Esophagitis Esophageal cancer Pulmonary cancer Esophageal cancer Esophageal cancer Esophageal cancer Chronic lymphatic leukemia Gastric lymphoma Gastric cancer Gastric cancer

Lesser omentum Celiac axis Hepatoduodenal ligament Between trachea and esophagus Between cardia and liver Celiac axis At the aortic arch Mediastinum/pulmonary artery Celiac axis Between atrium and pulmonary artery Celiac axis Para-aortic, by cardia Lesser omentum Lesser omentum

1.5 1.5 2.0 0.5 0.7 1.5 1.0 1.5 1.5 0.4 1.0 2/0 1.5 1.5

+ + + + + + + + + + + + + +

tween malignant and benign solid lesions in or outside the upper gastrointestinal tract, many questions still have to be answered. The indications for the technique have to be defined. It seems likely that the main indications may be demonstration of malignant lymph nodes for staging, and diagnosis of lesions in the mediastinum, pancreas, and common bile duct. In some cases, aspiration of a lymph node can be accomplished only by needle puncture through malignant lesions of the wall, and malignant contamination is therefore theoretically possible even with the stylet in place inside the needle. In cases of aspiration from two different lesions, we recommend the use of two different needles. The present results indicate a need for larger, controlled studies. What are the predictive values of EUS-guided aspiration biopsy of malignant lesions in 234

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the gastrointestinal tract and of solid lesions outside the gastrointestinal wall in larger series? In the present series, FNA biopsies of small lymph nodes have been quite successful in staging of malignant disease. It is hoped that, also in larger series, further studies will clarify whether EUS-guided biopsy of lymph nodes can improve diagnostic accuracy in staging of patients and what the role of EUS-guided aspiration biopsy of benign conditions may be. And finally, a comparison with other diagnostic modalities is needed. We will continue to work with the technique in order to answer these questions.

REFERENCES 1. Vilmann P, Khattar S, Hancke S. Endoscopic ultrasound examinationof the upper gastrointestinaltract usinga curvedarray transducer. A preliminaryreport. SurgEndosc 1991;5:7982. V O L U M E 41, NO. 3, 1995

2. AmouyalP, Amouyal G, Mompoint D, et al. Endosonography: promising method for diagnosis of extrahepatic cholestasis. Lancet 1989;2:1195-7. 3. RSsch T, Lorenz R, Bralg C, Classen M. Endoscopic ultrasonography in diagnosis and staging of pancreatic and biliary tumors. Endoscopy 1992;24(suppl 1):304-8. 4. Caletti G, Ferrari A, Brocchi E, Barbara L. Accuracy of endoscopic ultrasonography in the diagnosis and staging of gastric cancer and lymphoma. Surgery 1993;113:14-27. 5. Grimm H, Soehendra N, Hamper K, et al. Contribution of endosonography to preoperative staging in esophageal and stomach cancer. Chirurg 1989;60:684-9. 6. Lightdale CJ, Botet JF. Esophageal carcinoma: pre-operative staging and evaluation of anastomotic recurrence. Gastrointest Endosc 1990;36(2 suppl):Sll-6. 7. Tio TL, Cheng J, Wijers OB, et al. Endosonographic TNM staging of extrahepatic bile duct cancer: comparison with pathological staging. Gastroenterology 1991;100:1351-61. 8. Tio TL, Coene PP, Luiken GJ, et al. Endosonography in the clinical staging of esophagogastric carcinoma. Gastrointest Endosc 1990;36(2 suppl):S2-10. 9. Tio TL, Coene PP, van Delden OM, et al. Colorectal carcinoma: preoperative TNM classification with endosonography. Radiology 1991;179:165-70. 10. Heintz A, Mildenberger P, GeorgM, Braunstein S, Junginger T.

The feasibility of three-dimensional endoscopic ultrasonography: a preliminary report George Kallimanis, MD Brian S. Garra, MD T. Lok Tio, MD Brian Krasner, PhD Firas H. AI-Kawas, MD David E. Fleischer, MD Robert K. Zeman, MD Cuong C. Nguyen, MD Stanley B. Benjamin, MD

T h e d e v e l o p m e n t of endoscopic u l t r a s o n o g r a p h y (EUS) or so-called e n d o s o n o g r a p h y during the past decade has significantly e n h a n c e d the ability to image Received March 24, 1994. For revision June 13, 1994. Accepted July 19, 1994. From the Division of Gastroenterology and Department of Radiology, Georgetown University Medical Center, Washington, D.C. Presented in part at the annual meeting of the American Society for Gastrointestinal Endoscopy, May 1993, Boston, Massachusetts. Reprint requests: George Kallimanis, MD, Division of Gastroenterology, Georgetown University Medical Center, 3800 Reservoir Road, N. W., Washington, D.C. 20007-2197. 0016-5107/95/4103-o23553.0o + o GASTROINTESTINAL ENDOSCOPY Copyright © 1995 by the American Society for Gastrointestinal Endoscopy 37/69/59451

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Endoscopic ultrasonography in the diagnosis of regional lymph nodes in esophageal and gastric cancer--results of studies in vitro. Endoscopy 1993;25:231-5. 11. Tio TL, Wijers OB, Sars PR, et al. Preoperative TNM classification of proximal extrahepatic bile duct carcinoma by endosonography. Semin Liver Dis 1990;10:114-20. 12. R6sch T, Lorenz R, Braig C, et al. Endoscopic ultrasound in pancreatic tumor diagnosis. Gastrointest Endosc 1991;37:34752. 13. Rex DK, Tarver RD, Wiersema M, et al. Endoscopic transesophageal fine needle aspiration of mediastinal masses. Gastrointest Endosc 1991;37:465-8. 14. Lange P, Kock K, Laustsen J, et al. Endoscopic fine-needle aspiration cytology of the stomach. Endoscopy 1987;19:72-3. 15. Graham DY, Tabibian N, Michaletz PA, et al. Endoscopic needle biopsy: a comparative study of forceps biopsy, two different types of needles, and salvage cytologyin gastrointestinal cancer. Gastrointest Endosc 1989;35:207-9. 16. Kochhar R, Rajwanshi A, Malik AK, et al. Endoscopic fine needle aspiration biopsy of gastroesophageal malignancies. Gastrointest Endosc 1988;34:321-3. 17. Zargar SA, Khuroo MS, Mahajan R, et al. Endoscopic fine needle aspiration cytology in the diagnosis of gastro-oesophageal and colorectal malignancies. Gut 1991;32:745-8.

the gastrointestinal wall and its surrounding structures. 1-5 M a n y reports have d e m o n s t r a t e d the diagnostic capabilities of E U S and also its limitations. 613 For the investigator not familiar with EUS, the standard two-dimensional (2D) images it produces m a y be difficult to u n d e r s t a n d in terms of the topographic a n a t o m y of the gastrointestinal tract. T h r e e - d i m e n sional (3D) reconstruction has previously been applied to ultrasonographic, c o m p u t e d tomographic, and magnetic resonance imaging of cardiovascular and brain abnormalities. 14-21It has not, however, been applied to E U S imaging of the gastrointestinal tract. Such 3D E U S images m i g h t provide a more global representation of n o r m a l anatomic features and additional inform a t i o n concerning target lesions of interest. New software allows 3D rendering of digital endoscopic ultrasonographic d a t a (3D EUS). T h e aim of the s t u d y was to evaluate the ability of 3D E U S to elucidate both normal esophageal a n a t o m y and pathologic conditions accurately as c o m p a r e d with the information obtained by 2D EUS.

MATERIALS AND METHODS Patients Three-dimensional reconstructed endosonography was performed in 12 individuals (9 men, 3 women) with a mean age of 78.0 years (range, 46 to 82). The patients were divided into three groups. The first group consisted of 8 patients with a normal esophagus as shown by EUS (5 men and 3 women ranging in age from 56 to 81 years; mean, 63.7 years) and without a history of esophageal, pulmonary, or cardiac disease. Three patients had pancreatic lesions and 5 gastric lesions. The second group consisted of 1 man, 46 years of age, GASTROINTESTINAL ENDOSCOPY 2 3 5