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Usefulness of EUS-FNA with contrast-enhanced harmonic imaging for diagnosis of gallbladder tumor

 Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Date of Submission02-Jun-2020
Date of Acceptance02-Nov-2020
Date of Web Publication09-Feb-2021

Correspondence Address:
Masayuki Kitano,
Second Department of Internal Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama City, Wakayama 641-8509
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/EUS-D-20-00112

PMID: 33586687

How to cite this URL:
Tamura T, Yamashita Y, Itonaga M, Ashida R, Kitano M. Usefulness of EUS-FNA with contrast-enhanced harmonic imaging for diagnosis of gallbladder tumor. Endosc Ultrasound [Epub ahead of print] [cited 2021 May 8]. Available from: http://www.eusjournal.com/preprintarticle.asp?id=308925

Dear Editor,

It is usually difficult to obtain pathological evidence from gallbladder tumors before surgery and chemotherapy; however, histological diagnosis of gallbladder tumors is necessary for determining the treatment policy.[1] In recent years, EUS-FNA is reportedly useful to obtain a tissue for the diagnosis of gallbladder mass lesions. However, EUS-FNA for gallbladder tumor has a risk of bile leak and needle-track seeding by puncturing fluid space.[2],[3] We report a new technique of EUS-FNA with contrast-enhanced harmonic imaging (EUS-FNA-CHI) for accurately and safely obtaining tissue from a gallbladder mass to clarify the borderline between the gallbladder tumor and fluid spaces.[4] In this letter, we report usefulness of EUS-FNA-CHI for diagnosis of gallbladder tumor.

Our strategy for obtaining tissue from gallbladder tumors is first to try to obtain tissue from gallbladder tumors by endoscopic retrograde cholangiography (ERC) biopsy, then from liver or lymph node metastases by EUS-FNA, and finally from gallbladder tumors by EUS-FNA-CHI.

The detailed procedures for EUS-FNA-CHI were published elsewhere. Before EUS-FNA-CHI, we first manipulated the echoendoscope to detect the gallbladder mass lesion using fundamental B-mode [Figure 1]a. A few seconds after ultrasound contrast agent injection, gallbladder mass lesions typically became enhanced on contrast-enhanced harmonic mode, while fluid spaces, sludge, and necrotic tissue in the gallbladder remain unenhanced [Figure 1]b. If a nonenhanced space was observed on the puncture line, the puncture line was changed to avoid it [Figure 1]c. The enhanced part of the gallbladder tumor was targeted for EUS-FNA [Figure 1]d and [Figure 1]e.
Figure 1: EUS-FNA with contrast-enhanced harmonic imaging for gallbladder tumor. (a) Fundamental B-mode EUS showing a mass lesion in the gallbladder. There is no fluid space visible in the gallbladder under fundamental B-mode imaging. (b) The borderline between the gallbladder tumor and fluid space become clear under contrast-enhanced harmonic EUS (CH-EUS). (c) CH-EUS revealing the presence of a fluid space (yellow arrow) on the puncture line (dot line) that fundamental B-mode imaging failed to depict. (d) CH-EUS showing that the enhanced part of the gallbladder tumor is punctured by the needle (white arrow head) passing through the gallbladder wall. (e) Histological examination of tissue obtained by EUS-FNA showing inflammatory cell aggregation and gallbladder epithelium without atypical nuclear cell (H and E, ×400) (final diagnosis: xanthogranulomatus cholecystitis)

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Between September 2016 and December 2019, a total of 22 patients needed tissue for pathological evidence due to suspected gallbladder carcinoma at Wakayama Medical University. Among these patients, eight patients underwent EUS-FNA-CHI from gallbladder tumor. The mean mass lesion size was 35 mm along the longest axis (range: 20–85 mm). EUS-FNA-CHI obtained adequate tissue for pathological evidence in all eight patients. There were no serious procedure-related complications such as bile leakage or needle-track seeding [Table 1]. The average of follow-up period was 15.1 months in all patients; 9 and 19.2 months in those with and without undergoing cholecystectomy, respectively.
Table 1: Detailed summary of 8 patients who underwent endoscopic ultrasound-guided fine-needle aspiration for gallbladder tumor

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The final diagnoses of the gallbladder tumors were three gallbladder adenocarcinoma, one neuroendocrine carcinoma, one diffuse B-cell malignant lymphoma, one xanthogranulomatus cholecystitis, and two cholecystitis, all of which were correctly diagnosed by EUS-FNA-CHI [Table 1]. In particular, it properly diagnosed neuroendocrine carcinoma and malignant lymphoma, which are usually difficult to diagnose with only a cytology examination. The present report shows that EUS-FNA-CHI allows appropriate positioning the needle within the gallbladder tumor by avoiding fluid space, which may result in obtaining a higher volume of tissue. EUS-FNA has an advantage over bile cytology with ERCP in obtaining sufficient samples for histopathology and gene analysis to reveille phenotype and clue for special innovative drugs.[5] It would be mandatory to take sufficient materials in the patients who receive chemotherapy, particularly neoadjuvant chemotherapy for a tumor localized in the gallbladder. In conclusion, performing EUS-FNA-CHI may be a useful and safe method to obtain gallbladder tissue.


The present study was supported by grants from the Japan Society for Promotion of Science.

Financial support and sponsorship

The present study was supported by grants from the Japan Society for Promotion of Science.

Conflicts of interest

There are no conflicts of interest.

  References Top

Kumar R, Srinivasan R, Gupta N, et al. Spectrum of gallbladder malignancies on fine-needle aspiration cytology: 5 years retrospective single institutional study with emphasis on uncommon variants. Diagn Cytopathol 2017;45:36-42.  Back to cited text no. 1
Hijioka S, Hara K, Mizuno N, et al. Diagnostic yield of endoscopic retrograde cholangiography and of EUS-guided fine needle aspiration sampling in gallbladder carcinomas. J Hepatobiliary Pancreat Sci 2012;19:650-5.  Back to cited text no. 2
Hijioka S, Mekky MA, Bhatia V, et al. Can EUS-guided FNA distinguish between gallbladder cancer and xanthogranulomatous cholecystitis? Gastrointest Endosc 2010;72:622-7.  Back to cited text no. 3
Tamura T, Yamashita Y, Kawaji Y, et al. Endoscopic ultrasound-guided fine needle aspiration with contrast-enhanced harmonic imaging for diagnosis of gallbladder tumor (with video). J Hepatobiliary Pancreat Sci 2020; Ahead of print. [Doi 10.1002/jhbp.834].  Back to cited text no. 4
Kuwatani M, Sakamoto N. Evolution and a promising role of EUS-FNA in gene and future analyses. Endosc Ultrasound 2020;9:151-3.  Back to cited text no. 5


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  [Table 1]


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