Risks of Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Risks of Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Aspiration

Risks of Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Aspiration Sammy Ho, MD Endoscopic ultrasound (EUS) and EUS-guided fine ne...

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Risks of Endoscopic Ultrasound and Endoscopic Ultrasound-Guided Fine-Needle Aspiration Sammy Ho, MD Endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration (EUS-FNA) have become important tools in evaluation of patients with various clinical disorders, and are being increasingly utilized at many centers. EUS shares the risks and complications of other endoscopic procedures. This article addresses specific adverse effects and risks associated with EUS and EUS-FNA, mainly perforation, pancreatitis, bleeding, and infection. Measures to help minimize these risks will also be discussed. Tech Gastrointest Endosc 10:22-24. © 2008 Published by Elsevier Inc. KEYWORDS endoscopic ultrasound, endoscopic ultrasound guided fine needle aspiration, complications, perforation, pancreatitis, bleeding, infection

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ntroduced in the early 1980s, endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) have emerged as important modalities in the evaluation of various clinical disorders. Recent technological improvements in echoendoscopes have opened up the possibilities for performing more sophisticated procedures, such as EUSguided pancreatic cyst ablation, delivery of chemotherapeutic agents directly into tumors, lymphadenectomy, and the creation of anastomoses under EUS guidance. As the indications for EUS expand, a thorough understanding of its potential complications becomes increasingly important. EUS shares the risks and complications of other endoscopic procedures, including cardiovascular events, complications of sedation, and allergic reactions to medications. This discussion focuses on adverse effects and risks specifically associated with EUS, mainly perforation, pancreatitis, bleeding, and infection. Echoendoscopes have different mechanical characteristics compared with standard endoscopes. Currently available echoendoscopes have an ultrasound transducer at the distal end of the instrument. These transducers are not flexible, thus making the tip of the echoendoscope more rigid than that of a standard endoscope. The nonflexible distal segment can be up to 4 cm in length, which can make manipulation of echoendoscopes more challenging, and can contribute to some of the procedure-related complications, especially perforation. Upper gastrointestinal (GI) endoscopy with a standard upper endoscope carries a risk of perforation of 0.03%.1 Although available data are limited, perforation is theoretically more comMontefiore Medical Center, Bronx, NY. Address reprint requests to Sammy Ho, MD, Montefiore Medical Center, Division of Gastroenterology, Section of Pancreaticobiliary Services and Endoscopic Ultrasound, 111 East 210th Street, Bronx NY 10467. E-mail: [email protected]

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1096-2883/08/$-see front matter © 2008 Published by Elsevier Inc. doi:10.1016/j.tgie.2007.08.007

mon with EUS than with esophagogastroduodenoscopy (EGD). The increased risk can be partly accounted for by the echoendoscope design as described above. The tip of the echoendoscope may cause luminal perforation in areas of angulation (eg, oropharynx or apex of duodenal bulb), at points of stenosis (eg, esophageal cancer), or where a blind lumen exists (eg, pharyngeal or esophageal diverticulum). A survey of 86 physicians regarding their experience with cervical esophageal perforations reported 16 perforations among 43,852 examinations (0.003%) with 1 death (0.002% mortality)2; the majority (94%) of perforations occurred in patients older than 65 years of age. There was also evidence that perforation was more common early in an endosonographer’s experience. Twelve of the 16 perforations were caused by trainees or staff physicians with less than 1 year of experience with EUS. Compared with benign strictures, malignant esophageal strictures have been linked to an increased incidence of esophageal perforation after esophageal dilation.3 Approximately 15% to 40% of patients with esophageal cancer have a nontraversable esophageal tumor.4,5 Generally, dilation of such obstructing lesions is recommended, given the greater accuracy of EUS for T and N staging of traversable compared with nontraversable tumors. Initial studies reported perforation rates as high as 24% with esophageal dilation followed by immediate EUS6; more recent studies, however, have found this practice quite safe,5,6 probably because newer echoendoscopes are of smaller diameter than older generations instruments, and greater awareness of these potential complications has led to less aggressive dilation practices. In summary, although available data are limited, perforation is probably slightly more common with EUS than with EGD, largely because of echoendoscope design. Lack of operator experience, older patient age, and the presence of malignant esophageal strictures also may be risk factors for per-

Risks of EUS and EUS-FNA foration during EUS. According to the American Society for Gastrointestinal Endoscopy (ASGE), trainees must perform a minimum of 100 EUS-FNA procedures to be considered proficient in the procedure. The learning curve for learning to perform EUS-FNA is steep, however, and the level of experience needed to minimize complications is not yet known. Pancreatitis can occur after EUS-FNA of both solid and cystic lesions of the pancreas. In 1 pooled analysis of data from 19 American EUS centers, 14 cases of pancreatitis were documented among 4909 after EUS-FNA procedures on solid pancreatic mass lesions, an incidence of 0.3%7; most cases (71%) were classified as being of mild severity. Another study evaluated pancreatitis among 100 patients undergoing EUS-FNA (median 3.4 passes; range 2-9) and found a 2% rate of pancreatitis,8 defined as upper-abdominal pain accompanied by at least a 3-fold elevation of serum amylase or lipase. Both patients who developed pancreatitis after EUS-FNA had a history of acute pancreatitis, suggesting that such a history may be a risk factor for EUS-FNA-induced pancreatitis. Serum amylase and lipase levels were checked before and within 2 hours after the procedure, but serum levels of pancreatic enzymes are often elevated after EUS-FNA and, in most cases, have no clinical significance. It has been reported that pancreatitis after EUS-FNA is higher in patients with benign rather than malignant pancreatic diseases.9 The risk of pancreatitis can be reduced by limiting the number of needle passes, minimizing the amount of “normal” pancreatic parenchyma that must be traversed, and avoiding the pancreatic duct during EUS-FNA procedures. In general, pancreatitis that occurs following EUS-FNA is mild. The risk of bleeding with EUS relates mainly to performance of FNA. A small amount of luminal bleeding is often present endoscopically at FNA puncture sites, but generally is without clinical sequelae. EUS-induced extraluminal bleeding is rare, as endosonographers can avoid visible vessels detected by color flow Doppler when selecting a path for FNA. The incidence of bleeding was 0%3 to 0.4%10 in 2 prospective studies enrolling over 300 patients, and 1.3% in a retrospective study.11 In a prospective cohort study by Eloubeidi and coworkers,12 355 patients underwent EUS-FNA of solid pancreatic lesions without any identified significant bleeding episodes. Acute intracystic hemorrhage also can occur during EUS-FNA of cystic pancreatic lesions, but is usually without serious consequences, except for transient abdominal pain.13 Overall, hemorrhagic complications from EUS-FNA appear to be infrequent and largely self-limited. Procedural techniques that might help decrease these complications include limiting the number of FNA passes to the minimum necessary for diagnosis and using real-time Doppler ultrasound to identify and avoid vascular structures in the FNAneedle path. The frequency of bacteremia as a complication of EUSFNA has been studied prospectively in 3 separate trials. These studies, which comprised over 250 patients, did not find any statistically significant increase in the rate of bacteremia after biopsy.14-16 As infection rate is remarkably low, antibiotic prophylaxis is not necessary for FNA of solid lesions. In contrast, because of a relatively higher infection risk, antibiotic prophylaxis is advised for biopsy of pancreatic pseudocysts or cystic tumors.14 Technical issues also may affect the risk of cyst infection. Multiple needle passes into a

23 cyst appear to increase the risk of infection, in addition to failure to aspirate completely all of the cystic fluid. Overall, it can be argued that the risk of bacteremia after EUS-FNA is low and comparable with that of diagnostic endoscopy. Prophylactic antibiotics are not recommended for FNA of solid masses and lymph nodes. Most experts do, however, recommend prophylactic antibiotics, as well as a short postprocedure course of antibiotics, after EUS-FNA of pancreatic cystic lesions and lesions within the perirectal space, such as a lymph node.18 EUS-FNA in the region of the pancreatic head can result in iatrogenic bile duct injury with subsequent bile peritonitis. One patient developed bile peritonitis after EUS-FNA of a pancreatic head mass, when the needle inadvertently perforated the distal common bile duct.14 During a study of the use of EUS-FNA to obtain bile directly from the gallbladder to identify patients with microlithiasis, bile peritonitis developed in two of the first three patients enrolled; this experience resulted in termination of the study.15 There is a theoretical risk of tumor seeding along the needle track when performing EUS-FNA, and tumor dissemination after EUS-FNA has been reported in two cases.16,17 Nevertheless, EUS-FNA has been shown to have a decreased risk of peritoneal seeding with malignant cells as compared with computed tomography-guided FNA (2.2% versus 16.3%).18 This decreased risk is conceivably due to a shorter needlepath. Because of the concern over needle-tract seeding with transcutaneous aspiration, the American Joint Committee on Cancer has recommended EUS-FNA as the preferred sampling method in pancreatic masses, if it is available. To diminish the risk of EUS-FNA tumor spread, FNA should be performed only when the results are likely to affect patient management decisions substantially. When possible, EUS-FNA sites should be chosen such that needle-to-target distances are minimal and trajectory paths are likely to be included as part of the resection specimens in patients subsequently undergoing potentially curative surgery. In summary, EUS and EUS-FNA have become important tools in evaluation of patients with various clinical disorders. With more than 10 years experience, the collective published data suggest that EUS is a safe modality. There are also measures that one can take to minimize complications when performing EUS and EUS-FNA. In light of rapid advances in EUS interventional techniques, the safety of all types of EUS-related procedures and efforts to minimize complications need to be re-examined periodically.

References 1. Eisen GM, Baron TH, Dominitz JA, et al: Complications of upper GI endoscopy. Gastrointest Endosc 55:784-793, 2002 2. Das A, Sivak MV Jr, Chak A: Cervical esophageal perforation during EUS: a national survey. Gastrointest Endosc 53:599-602, 2001 3. Schulze S, Moller Pedersen V, Hoier-Madsen K: Iatrogenic perforation of the esophagus. Causes and management. Acta Chir Scand 148:679682, 1982 4. Wallace MB, Hawes RH, Sahai AV, et al: Dilation of malignant esophageal stenosis to allow EUS guided fine-needle aspiration: safety and effect on patient management. Gastrointest Endosc 51:309-313, 2000 5. Pfau PR, Ginsberg GG, Lew RJ, et al: Esophageal dilation for endosonographic evaluation of malignant esophageal strictures is safe and effective. Am J Gastroenterol 85:2813-2815, 2000 6. Van Dam J, Rice T, Catalano M, et al: Dilation of malignant stricture is

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12. Eloubeidi MA, Tamhane A, Varadarajulu S, et al: Frequency of major complications after EUS-guided FNA of solid pancreatic masses: a prospective evaluation. Gastrointest Endosc 63:622-629, 2006 13. Varadarajulu S, Eloubeidi M: Frequency and significance of acute intracystic hemorrhage during EUS-FNA of cystic lesions of the pancreas. Gastrointest Endosc 60:631-635, 2004 14. Ader DG, Jacobson BC, Davila RE, et al: ASGE guidelines: complications of EUS. Gastrointest Endosc 61:8-12, 2005 15. Jacobson BC, Waxman I, Parmar K, et al: Endoscopic ultrasoundguided gallbladder bile aspiration in idiopathic pancreatitis carries a significant risk of bile peritonitis. Pancreatology 2:26-29, 2002 16. Shah JN, Fraker D, Guerry D, et al: Melanoma seeding of an EUSguided fine needle track. Gastrointest Endosc 59:923-924, 2004 17. Hirooka Y, Goto H, Itoh A, et al: Case of intraductal papillary mucinous tumor in which endosonography-guided fine-needle aspiration biopsy caused dissemination. J Gastroenterol Hepatol 18:1323-1324, 2003 18. Micames C, Jowell PS, White R, et al: Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUSguided FNA vs. percutaneous FNA. Gastrointest Endosc 58:690-695, 2003