Endoscopic Ultrasound-Guided Fine-Needle Aspiration in the Evaluation of Gallbladder Masses

• Introduction
• Patients and Methods
• Results
• Discussion
• References

Background and Study Aims: There are very few data on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of gallbladder masses. The aim of this study was to assess the utility and safety of EUS-FNA in the evaluation of patients with gallbladder masses.
Patients and Methods: Six patients who underwent EUS-FNA of gallbladder masses over a 2-year period between 2002 and 2004 were studied retrospectively. Reports of endoscopic ultrasound (EUS) procedures, EUS images, cytology results, and clinical records were reviewed. Abdominal computed tomography (CT) prior to EUS had revealed a definitive gallbladder mass in only one of the six patients and no gallbladder masses were identified in any of the patients who had undergone prior transabdominal ultrasound.
Results: At EUS, all the patients were found to have an echo-poor mass arising from the gallbladder wall or within the lumen of the gallbladder. EUS-FNA of the gallbladder masses revealed adenocarcinoma in five patients and benign disease in one patient. After a mean follow-up period of 127 days (range 90 - 187 days), three patients had died, two were undergoing palliative chemoradiotherapy, and one had been confirmed as having chronic cholecystitis at surgery. No complications occurred.
Conclusions: In patients with obstructive jaundice and equivocal ultrasound or CT findings, evaluation of the gallbladder for the presence of a primary malignancy by EUS is useful. In patients with gallbladder masses, EUS-FNA can be performed safely and can help to make a definitive diagnosis.

Introduction

In the United States, gallbladder cancer is the fifth most common cancer of the gastrointestinal tract and is usually discovered incidentally in patients who are undergoing explorative investigations for cholelithiasis [1] [2]. The median survival of these patients is poor (19 months), even for those with stage I disease in which tumor is confined to the gallbladder [3].

Traditionally, the diagnosis of gallbladder cancer is established by computed tomography- (CT-) guided or ultrasound-guided biopsy. In a series of 89 patients with gallbladder polyps who underwent both endoscopic ultrasound (EUS) and transabdominal ultrasound, the sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of gallbladder cancer by EUS were 92 %, 88 %, 76 %, and 97 % respectively, compared with 54 %, 54 %, 54 %, and 95 % for the same parameters for diagnosis by transabdominal ultrasound [4]. EUS also has the advantage of being able to detect regional metastases because it allows visualization of the porta hepatis and peripancreatic regions [5] [6]. Apart from one recent case series [7], there are no data available on the use of EUS-guided fine-needle aspiration (EUA-FNA) for evaluating patients with gallbladder cancer. The lack of data in this field may be accounted for by concern about the potential development of biliary peritonitis associated with EUS-FNA [8]. We report our experience with EUS-FNA of gallbladder masses, with regard to its clinical value, safety, and diagnostic accuracy.

Patients and Methods

The endoscopy database was searched for all patients who had undergone EUS-FNA of gallbladder masses over a 2-year period between February 2002 and February 2004. The medical records of the patients who were identified were reviewed and clinical information, reports of imaging studies, and EUS, surgical, and cytopathology reports were assessed. In order to assess the long-term outcome, follow-up data to May 2004 were obtained by contacting the patients or their family members by telephone. Immediate complications (within 24 hours) and late complications (up to 30 days) were evaluated prospectively by a research assistant. EUS was performed first with a radial echo endoscope (Olympus GF-UM 130; OLympus America Inc., Melville, New York) and the fine-needle aspiration (FNA) was then performed using a curved linear-array echo endoscope (Olympus UC-30P; Olympus America Inc., Melville, New York, USA). FNA samples were obtained using a 22-gauge needle (Wilson-Cook, Winston-Salem, North Carolina, USA) and smeared onto slides for review by an on-site cytopathologist. For the sake of this analysis, we relied on the final diagnosis submitted on the official report.

Results

Six patients were included in the study (five men, one woman; median age 72, range 56-86). They had all been referred for evaluation of obstructive jaundice. The clinical characteristics of the patients are summarized in Table [1]. EUS was performed in order to further evaluate CT findings that had revealed a gallbladder mass in one patient, intrahepatic biliary dilatation without a definite mass in two patients, a porta hepatis mass in one patient, a liver metastasis from an unknown primary in one patient, and a retroperitoneal mass that was thought to be a metastatic deposit in one patient. Four of the six patients had undergone transabdominal ultrasound as part of their initial work-up: one patient was found to have dilated intrahepatic ductal radicles and three had a contracted gallbladder.

In all six patients, EUS revealed an echo-poor mass with irregular borders within the gallbladder lumen or arising from the gallbladder wall (Figure [1], [2]). Four patients had gallstones and two had hilar lymphadenopathy in association with the mass. The mean size of the mass lesion was 40 mm along its longest axis (range 18 - 74 mm). FNA yielded adequate tissue in all patients (Figure [3]) and a preliminary diagnosis was established by the on-site cytopathologist in all cases: adenocarcinoma was found in four patients and neutrophils in association with fibrosis in one patient; FNA of the gallbladder mass was not possible in one patient due to the presence of collateral vasculature, but FNA of the hilar lymph node (12 mm × 6 mm) in this patient revealed adenocarcinoma. The mean number of passes required to establish a diagnosis was two (ranging from one to five).

After a mean follow-up period of 127 days (range 90 - 187 days), three patients had died of advanced malignancy, two patients were undergoing palliative chemoradiotherapy for inoperable disease, and the patient with neutrophils and fibrosis on EUS-FNA had been diagnosed with chronic cholecystitis at surgery. There were no immediate or late complications.

Discussion

EUS-FNA of gallbladder masses is safe and establishes a diagnosis when the findings of other conventional investigative techniques, such as transabdominal ultrasound or CT, are equivocal. CT and transabdominal ultrasound have accuracies of 40 % and 70 % respectively for diagnosing gallbladder cancer [9] [10]. However, the accuracy of these techniques for detecting regional lymph node involvement and local spread is poor [9] [11]. Transabdominal ultrasound-guided FNA has a specificity of 100 % and sensitivity of 88 % for diagnosing cancer in patients with large gallbladder masses [9] [12]. Percutaneous FNA, however, is associated with risks such as minor abdominal pain (4.5 %) and bile peritonitis (1 % - 6 %) [12] [13]. All six patients in our study had undergone prior CT and four patients had had a transabdominal ultrasound study as part of their initial work-up, but a definite gallbladder mass was identified in only one patient (on CT).

EUS is more accurate than extracorporeal ultrasound for visualizing the gallbladder [14]. The transducer frequency used in conventional sonography (3.5 MHz) is lower than that used for EUS (7.5 MHz), which means that the image obtained by EUS is clearer. In addition, EUS is not limited by the presence of gas in the bowel. As with transabdominal ultrasound, EUS findings that are suggestive of gallbladder cancer include a mass protruding into the gallbladder lumen, a fixed mass in the gallbladder wall, loss of the interface between the gallbladder and the liver, and direct liver infiltration [15]. One limitation of EUS is its limited ability to determine the depth of tumor invasion (77 % accuracy in one series, [16]). This inaccuracy is also encountered with other staging modalities such as transabdominal ultrasound (USD)s, CT, and magnetic resonance imaging [9] [11] [17]. In one of the six patients, in whom FNA of the gallbladder mass itself was not possible, a diagnosis of adenocarcinoma was made from examination of hilar lymph node aspirate. This ability to sample regional lymph nodes should improve staging accuracy further as metastasis to lymph nodes in gallbladder cancer indicates stage III disease, irrespective of the depth of tumor invasion.

The reluctance of endosonographers to perform FNA of gallbladder masses stems from a prior report by Jacobson et al. of three patients with idiopathic pancreatitis who underwent EUS-FNA of the gallbladder [7]. Although microlithiasis was diagnosed in one patient, two patients developed bile peritonitis. We did not encounter complications following EUS-FNA of gallbladder masses in any patient. It is likely that patients with a diseased gallbladder have a thick fibrotic wall that guards against bile spillage into the peritoneum after FNA of mass lesions.

In summary, evaluation of the gallbladder at EUS may be useful in demonstrating a primary lesion in patients presenting with malignant obstructive jaundice of unclear etiology. Both the current study and that by Jacobson et al. [7] of EUS-FNA of gallbladder masses involved a small number of patients. Our experience, although limited, indicates that the technique is safe and has high diagnostic accuracy. Given this preliminary data, further evaluation by larger studies is justified.

References

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S. Varadarajulu, M.D.

Division of Gastroenterology-Hepatology, University of Alabama at Birmingham ·

410 Lyons Harrison Research Building · 1530 3rd Ave South · Birmingham · Alamabma · 35294-0007 · USA ·

Fax: +1-205-975-6381

Email: svaradarajulu@yahoo.com

References

• 1 Piehler J M, Crichlow R W. Primary carcinoma of the gallbladder.  Surg Gynecol Obstet. 1978;  147 929-942
  PubMedSearch in Google Scholar
• 2 Hamrick R E Jr, Liner F J, Hastings P R, Cohn I Jr. Primary carcinoma of the gallbladder.  Ann Surg. 1982;  195 270-273
  PubMedSearch in Google Scholar
• 3 Henson D, Albores-Saavedra J, Corle D. Carcinoma of the gallbladder.  Cancer. 1992;  70 1493-1497
  PubMedSearch in Google Scholar
• 4 Azuma T, Yoshikawa T, Araida T, Takasaki K. Differential diagnosis of polypoid lesions of the gallbladder by endoscopic ultrasonography.  Am J Surg. 2001;  181 65-70
  CrossrefPubMedSearch in Google Scholar
• 5 Fujita N, Noda Y, Kobayashi G. et al . Diagnosis of the depth of invasion of gallbladder carcinoma by EUS.  Gastrointest Endosc. 1999;  50 659-663
  PubMedSearch in Google Scholar
• 6 Sadamoto Y, Kubo H, Harada N. et al . Preoperative diagnosis and staging of gallbladder carcinoma by EUS.  Gastrointest Endosc. 2003;  58 536-541
  CrossrefPubMedSearch in Google Scholar
• 7 Jacobson B C, Pitman M B, Brugge W R. EUS-guided FNA for the diagnosis of gallbladder masses.  Gastrointest Endosc. 2003;  57 251-254
  CrossrefPubMedSearch in Google Scholar
• 8 Jacobson B, Waxman I, Parmar K. et al . Endoscopic ultrasound-guided gallbladder bile aspiration in idiopathic pancreatitis carries a significant risk for bile peritonitis.  Pancreatology. 2002;  2 26-29
  CrossrefPubMedSearch in Google Scholar
• 9 Pandey M, Sood B P, Shukla R C, Aryya N C. Carcinoma of the gallbladder: role of sonography in diagnosis and staging.  J Clin Ultrasound. 2000;  28 227-232
  CrossrefPubMedSearch in Google Scholar
• 10 Oikarinen H, Paivansalo M, Lahde S. et al . Radiological findings in cases of gallbladder carcinoma.  Eur J Radiol. 1993;  17 179-183
  CrossrefPubMedSearch in Google Scholar
• 11 Kim B S, Ha H K, Lee I J. et al . Accuracy of CT in local staging of gallbladder carcinoma.  Acta Radiol. 2002;  43 71-76
  PubMedSearch in Google Scholar
• 12 Zargar S, Khuroo M, Mahajan R. et al . US-guided fine-needle aspiration biopsy of gallbladder masses.  Radiology. 1991;  179 275-278
  CrossrefPubMedSearch in Google Scholar
• 13 Wu S, Lin K, Soon M, Yeh K. Ultrasound-guided percutaneous transhepatic fine-needle aspiration cytology of gallbladder polypoid lesions.  Am J Gastroenterol. 1996;  91 1591-1594
  PubMedSearch in Google Scholar
• 14 Sugiyama M, Atomi Y, Yamato T. Endoscopic ultrasonography for differential diagnosis of polypoid gallbladder lesions: analysis in surgical and follow-up series.  Gut. 2000;  46 250-254
  CrossrefPubMedSearch in Google Scholar
• 15 Wibbenmeyer L A, Sharafuddin M J, Wolverson M K, Heiberg E V. Sonographic diagnosis of unsuspected gallbladder cancer: imaging findings in comparison with benign gallbladder conditions.  AJR Am J Roentgenol. 1995;  165 1169-1174
  PubMedSearch in Google Scholar
• 16 Mitake M, Nakazawa S, Naitoh Y. et al . Endoscopic ultrasonography in the diagnosis of the extent of gallbladder carcinoma.  Gastrointest Endosc. 1990;  36 562-566
  PubMedSearch in Google Scholar
• 17 Tseng J, Wan Y, Hung C. et al . Diagnosis and staging of gallbladder carcinoma: evaluation with dynamic MR imaging.  J Clin Imaging. 2001;  26 177-182
  PubMedSearch in Google Scholar

S. Varadarajulu, M.D.

Division of Gastroenterology-Hepatology, University of Alabama at Birmingham ·

410 Lyons Harrison Research Building · 1530 3rd Ave South · Birmingham · Alamabma · 35294-0007 · USA ·

Fax: +1-205-975-6381

Email: svaradarajulu@yahoo.com