Endoscopic Ultrasound–Guided Fine Needle Aspiration Cytology of ...

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AJG – September, 2003 EUS-FNA Cytology of Solid Liver Lesions 1979 FNA. All imaging had been performed within 45 days of the EUS examination. Of these 42 lesions, EUS-FNA detected malignancy in 17 (41%) when prior imaging of the liver by CT alone (n 13), transabdominal ultrasound (US) alone (n 1), or both (n 3) were normal. For the 32 patients in whom CT alone was performed, EUS-FNA initially detected a malignancy in 13 (41%). For the nine patients in whom CT and US were both performed, EUS-FNA initially detected malignancy in three (33%). The mean size of the 17 malignant liver lesions detected initially by EUS-FNA was 12.6 mm (range 3–26 mm). Of these 17, six (35%) were 1 cm in diameter. Clinical Impact of EUS-FNA of the Liver For the 45 patients with malignant cytology, EUS-FNA had (by protocol definition) a clinical impact in all patients. EUS-FNA changed management, however, in only 38 (84%) of these patients, because in seven cases (16%) tumor was upstaged but did not change overall patient management. EUS-FNA provided the initial diagnosis of malignancy in 35 patients (78%) and avoided surgery in 12 (27%). Of the 35 patients in whom EUS-FNA made the initial diagnosis of malignancy, 34 (97%) had metastases and one (3%) had a hepatocellular carcinoma. In 25 patients (55%), the FNA provided both the primary diagnosis and upstaged the malignancy. In nine subjects (20%), EUS-FNA made the initial diagnosis, upstaged the tumor, and prevented surgery. Three EUS-FNAs (7%) were diagnostic in which previous CT-FNA was benign (two of three) or nondiagnostic (one of three). In three patients with nonmalignant EUS-FNA aspirates, malignancy was later confirmed by surgery (n 2) or percutaneous biopsy (n 1). Follow-Up After EUS-FNA Of the 45 patients with malignant cytology from EUS-FNA, 40 have died, with a mean time to death after EUS-FNA of 135 days (range 7–754 days). The patient who died 7 days after EUS-FNA expired in his sleep outside the hospital without any apparent adverse consequence from EUS-FNA; however, no autopsy was performed. The patient who lived 754 days had metastatic pancreatic cancer and enrolled in an experimental chemotherapy protocol at another institution. The longest survival otherwise was 298 days. Five patients remain alive with a mean follow-up of 64 days (range 30–140 days). The mean time to death from metastatic pancreatic adenocarcinoma to the liver was 113 days (n 31; range 7–754 days). DISCUSSION The results of this study demonstrate that EUS-guided FNA of solid hepatic masses is sensitive, safe, and has a significant impact on patient management when malignancy is diagnosed. In our series, the sensitivity of EUS-FNA for the diagnosis of malignancy ranged from 82% to 94%. Although it may be presumed that we obtained no false positive results when testing aspirates, the inability to histologically corroborate this does not allow for calculation of specificity. A previous report of 14 patients that underwent EUS-FNA of liver metastases described a sensitivity and specificity of 100% and 100% for the diagnosis of malignancy (11). To our knowledge, however, our study is the first report of the test characteristics of EUS-FNA of the liver that includes both malignant and benign hepatic lesions. The sensitivity of the EUS-FNA of the liver we report is similar to previous series that describe the sensitivity of EUS-FNA of pancreatic malignancy (9, 15–17) and P-FNA of liver tumors (2, 18–20). Despite the good sensitivity of EUS-FNA of liver tumors, we obtained three false negative results. Therefore, follow-up percutaneous biopsy or intraoperative evaluation is warranted when the diagnosis of malignancy in the liver is strongly suspected and would significantly affect patient management. The mean number of overall passes performed for the diagnosis of hepatic lesions (n 3.2; range 1–8) is slightly higher in our series than has been previously reported (11). The exact reason for this difference is not clear, although it is not significantly different from the number required for ultrasound-guided P-FNA of small hepatic masses (21). In a series of 14 patients with EUS-FNA of a malignant liver lesion, Nguyen et al. reported a mean of 2.0 (range 1–5) passes for the diagnosis of malignancy (11). The presence of a cytopathologist on-site was implied, as interpretation of specimens was performed before making repeated passes. We also have a cytotechnologist or cytopathologist available on site to assess the adequacy of obtained specimens. Because the diagnosis of metastatic disease is clinically relevant and initial air-dried preparations are sometimes difficult to interpret, we will often repeat another pass to ensure that cytology is sufficient to render a diagnosis if the adequacy of a specimen is initially interpreted as “suspicious” but not diagnostic of malignancy. We found no statistically significant difference between the numbers of passes required for the diagnosis of benign (n 3.2; range 1–8) or malignant (n 3.5; range 1–8) lesions. In addition, no difference existed between the number of passes required during the first or second half of the study. This implies that increased experience with this technique may not decrease the number of passes needed to obtain an accurate cytological diagnosis. Despite the relatively higher number of passes performed in this study, we observed no complications after EUS-FNA of the liver. In a large international survey of 167 cases describing EUS-FNA of the liver, however, six complications (4%) were described (12). These complications included one death in a patient who underwent EUS-FNA of the liver despite a suspected obstructed biliary stent. Other complications noted were bleeding, abdominal pain, and fever. Although it is standard practice for gastroenterologists to observe patients in the right lateral decubitus position for several hours after percutaneous biopsy of the liver, we discharge stable patients within 60–75 min after EUS-
1980 DeWitt et al. AJG – Vol. 98, No. 9, 2003 FNA of the liver. Furthermore, we do not routinely place patients on their right side during recovery before discharge. A recent series (5) describing the use of P-FNA in the diagnosis of 216 liver tumors reported the occurrence of implantation metastases in seven patients (3%) a median 4 months (range 2–49 months) after P-FNA of liver masses from colorectal cancer (n 5), gallbladder carcinoma (n 1), and a hepatoma (n 1). In addition, the implantation metastases caused major problems locally and were fatal in four patients. This complication has not been described after EUS-FNA of the liver. The true incidence of implantation metastases after EUS-FNA of the liver, however, is difficult to estimate, inasmuch as hepatic metastases from pancreatic malignancy (which comprise 87% of malignancies in our study) usually carry a dismal prognosis and are managed nonoperatively. Therefore, as the overwhelming majority of patients diagnosed with of hepatic metastases after EUS- FNA of the liver do not undergo intended curative resection, the true incidence of this complication is not known. The most common malignancies diagnosed by P-FNA (colorectal metastases and primary hepatomas) are often managed surgically with curative intent. We believe that these fundamental differences partially explain the disparity in reported incidence of implantation metastases between EUS- FNA and P-FNA of liver masses. Studies comparing the diagnostic accuracy and complications EUS-FNA and P- FNA of all types of suspected liver tumors are needed to resolve these issues. The overall sensitivity of transabominal US for the detection of liver metastases is reportedly between 80% and 90% (22, 23). Recent studies using helical CT and magnetic resonance imaging, however, show that noninvasive imaging is relatively insensitive for lesions 1 cm(24–26). By EUS and EUS-FNA, we detected 17 malignant hepatic lesions (mean 12.6 mm, range 3–26 mm) with a previously normal CT alone (n 13), CT and US (n 3), or US alone (n 1). Of these, six (35%) were 1 cm in diameter. These 17 lesions were found in 41% of the 42 patients with available radiographic imaging information performed before EUS. Nguyen et al. (11) reported that CT performed before EUS-FNA of the liver failed to detect liver lesions in 11 of 14 patients (79%). Collectively, these results demonstrate the utility of EUS-FNA for the detection of malignant liver lesions that have been missed by prior radiographic imaging. Further comparative studies are needed to determine whether other imaging modalities such as fluorine-18 fluorodeoxyglucose positron emission tomography (27), magnetic resonance imaging (28), harmonic ultrasound imaging (29), or ultrasound contrast agents (30) offer any advantages over EUS for detection of occult or subcentimeter liver metastases. When compared with benign lesions, we found that malignant lesions detected by EUS-FNA of the liver were more likely to have regular margins (60% vs 27%; p 0.02) and to be accompanied by at least one other lesion detected on EUS (38% vs 9%; p 0.03). Furthermore, no statistically significant difference was found with regard to site of biopsy (p 0.57), size (p 0.70), echogenicity (p 0.36), or number of passes performed (p 0.44) for these lesions. Although EUS features of malignant lymphadenopathy have been described (31), to our knowledge the endosonographic features for malignant liver lesions have not been previously reported. These findings may help to guide decision making and assessment of the risk/benefit ratio of EUS-FNA of hepatic masses. In conclusion, the results of our study show that the sensitivity of EUS-FNA of the liver for the diagnosis of malignancy ranges from 82% to 94% and that, contrary to previous reports, it is a safe procedure. When malignancy is diagnosed, EUS-FNA of the liver significantly affects patient management and implies a poor overall prognosis. EUS features predictive of malignant hepatic masses are the presence of regular outer margins and the detection of two or more lesions. In this series, EUS and EUS-FNA detected malignant liver tumors that were not seen by CT or US (or both) in 41% of subjects. Therefore, surveillance of the entire liver is indicated during evaluation of known or suspected malignancy. Prospective studies are needed to compare the accuracy and complication rate of EUS-FNA and P-FNA for the diagnosis of liver tumors. Reprint requests and correspondence: John M. DeWitt, M.D., Department of Medicine, Division of Gastroenterology, Indiana University Medical Center, 550 N. University Boulevard, UH 4100, Indianapolis, IN 46202-5121. Received Nov. 11, 2002; accepted Jan. 30, 2003. REFERENCES 1. Tatsuta M, Yamamoto R, Kasugai H, et al. Cytohistologic diagnosis of neoplasms of the liver by ultrasonically guided fine-needle aspiration biopsy. Cancer 1984;54:1682–6. 2. Buscarini L, Fornari F, Bolondi L, et al. Ultrasound-guided fine-needle biopsy of focal liver lesions: Techniques, diagnostic accuracy and complications. A retrospective study on 2091 biopsies. J Hepatol 1990;11:344–8. 3. Edoute Y, Ben-Haim S, Brenner B, et al. Fatal hemoperitoneum after fine-needle aspiration of a liver metastases. Am J Gastroenterol 1992;87:358–9. 4. Kowdley KV, Aggarwal A, Sachs PB. Delayed hemorrhage after percutaneous liver biopsy: Role of therapeutic angiography. J Clin Gastroenterol 1994;19:50–3. 5. Ohlsson B, Nilsson J, Stenram U. Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumors. Br J Surg 2002;89:757–62. 6. Goletti O, Chiarugi M, Buccianti P, et al. Subcutaneous implantation of liver metastasis after fine needle biopsy. Eur J Surg Oncol 1992;18:636–7. 7. Scheele J, Alterndorf-Hofmann A. Tumor implantation from needle biopsy of hepatic metastases. Hepato-Gastroenterology 1990;37:335–7. 8. Andersson R, Andren-Sanberg A, Lundstedt C, et al. Implantation metastases from gastrointestinal cancer after percutaneous puncture or biliary drainage. Eur J Surg 1996;162:551–4. 9. Wiersema MJ, Vilmann P, Giovannini M, et al. Endosonography-guided fine needle aspiration biopsy: Diagnostic accu-
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