Endoscopic ultrasonography-guided brushing increases cellular diagnosis of pancreatic cysts: A prospective study

doi:10.1016/j.dld.2010.07.009

Digestive and Liver Disease

Volume 42, Issue 12, December 2010, Pages 877-881

https://doi.org/10.1016/j.dld.2010.07.009 Get rights and content

Abstract

Background

The diagnosis of pancreatic cystic lesions is still a challenge.

Aim

To prospectively investigate the usefulness and safety of EUS-guided cytology brushing (EUS BR) in the cellular diagnosis of pancreatic cysts.

Methods

Cysts >15 mm were sampled with a 19G needle. The fluid was aspirated and processed for cytology. The brush was introduced to scrub the cystic wall and processed as standard brushings. Antibiotic prophylaxis was administered. Complications were assessed in the first 24 h and 7 days after the procedure.

Results

30 patients were included. In 8 patients the technique failed for technical reasons. EUS BR provided with a cellular diagnosis in 20/22 cases (91%). The EUS BR was superior to the aspirated fluid for detecting diagnostic cells (73% vs. 36%, p = 0.08) and mucinous cells (50% vs. 18%, p = 0.016). In the 8 patients operated on, the specimen was consistent with EUS BR diagnosis. Three patients (10%) had complications, one of them a subacute retroperitoneal haemorrhage in a patient on anticoagulation therapy who died for complications 1 month later.

Conclusions

EUS BR increases cellular diagnosis of pancreatic cystic lesions as compared with fluid analysis, mainly in mucinous lesions. Its use is not recommended in patients under anticoagulation therapy.

Introduction

The management of cystic lesions of the pancreas is a clinical challenge. Mucinous cystic lesions have a known risk of malignant degeneration that must be kept in mind when taking decisions and planning follow-up. Therefore, the differentiation between benign and malignant or potentially malignant cystic lesions of the pancreas is crucial in the management of this group of patients [1].

In the last years, the improvement of cross-sectional imaging techniques and a better understanding of the appearance of the cystic lesions of the pancreas have caused a dramatic increase in the incidence of these lesions [2]. Among the cystic neoplasms, serous cystadenoma, mucinous cystic neoplasms and intraductal papillary-mucinous neoplasms account for the majority of the pancreatic cystic lesions encountered in clinical practice, with an incidence of 32–39%, 10–49%, and 21–33%, respectively [3]. Besides some typical cases, a high percentage of these lesions do not present morphological characteristics clear enough to diagnose or exclude a mucinous neoplasm [4]. Since imaging alone does not allow in most cases differentiating between benign and malignant or pre-malignant lesions, the possibility of obtaining a cytological diagnosis is of main importance.

EUS has largely demonstrated to be a useful tool for the evaluation of cystic lesions of the pancreas [5], [6], [7]. The main advantage of EUS is its ability to safely perform FNA under real-time guidance, even in focal lesions of small size. However, the poor cellularity typically obtained from the aspirated fluid of a cyst limits the performance of the cytological exam in these lesions [8], [9].

A new, through-the-needle cytological brush system, the EchoBrush that seeks to solve the limitations of EUS FNA by providing more cells, has recently been approved for use during EUS evaluation of the cystic lesions of the pancreas [10]. Although data are limited, EUS-guided cytology brushing (EUS BR) seems to be superior to conventional FNA in this setting and could be useful for the diagnosis of pancreatic cystic lesions [10], [11], [12].

Our hypothesis is that EUS BR may increase the cellular diagnosis of the cystic lesions of the pancreas as compared with the standard fluid aspiration. Therefore, this study was undertaken to investigate the usefulness and safety of EUS BR in the cellular diagnosis of the cystic lesions of the pancreas.

Section snippets

Study design

This prospective study included all consecutive patients with pancreatic cysts examined by EUS between May 2007 and July 2008 who met the following inclusion criteria: (1) diameter of the cyst > 15 mm, (2) platelet count > 50,000 and/or prothrombine time > 50% and (3) informed consent to participate.

Complications were prospectively investigated. The patients were hospitalized and carefully monitored 24 h after the EUS procedures, and data concerning post-procedural abdominal pain, bleeding, fever, or

Results

A total of 30 consecutive cystic lesions of the pancreas met the inclusion criteria and were included in the study. Characteristics of the pancreatic cysts are shown in Table 1.

In 8 patients, technical reasons prevent from completion of EUS BR procedure: the cyst could not be punctured because of its location in the head of the pancreas (n = 6) or its size in the lower limit (n = 2) that hampered the penetration of the 19G needle. Therefore, the final sample size is 22 pancreatic cystic lesions. In

Discussion

It is known that EUS allows an excellent visualization of the cystic lesions of the pancreas as well as to perform FNA under real-time guidance is deemed necessary. A variety of studies have assessed the role of EUS in discriminating benign pancreatic cysts from malignant or potentially malignant cystic lesions, mainly mucinous neoplasms. However, unless a solid mass or invasive tumour is seen, morphological features do not appear to be specific enough to differentiate between them [15], [16].

Conflict of interest

None declared.

References (24)

W.R. Brugge
Management and outcomes of pancreatic cystic lesions
Dig Liver Dis
(2008)
W.R. Brugge
Evaluation of pancreatic cystic lesions with EUS
Gastrointest Endosc
(2004)
F. Gress et al.
Endoscopic ultrasound characteristics of mucinous cystic neoplasms of the pancreas
Am J Gastroenterol
(2000)
N.H. Ahmad et al.
Interobserver agreement among endosonographers for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions
Gastrointest Endosc
(2003)
W.R. Brugge et al.
Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study
Gastroenterology
(2004)
A Khalid et al.
The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology
Clin Gastroenterol Hepatol
(2005)
J.L. Frossard et al.
Performance of endosonography-guided fine needle aspiration and biopsy in the diagnosis of pancreatic cystic lesions
Am J Gastroenterol
(2003)
F. Maire et al.
Intraductal papillary mucinous tumors of the pancreas: the preoperative value of cytologic and histopathologic diagnosis
Gastrointest Endosc
(2003)
M.J. Wiersema et al.
Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment
Gastroenterology
(1997)
M.J. Levy et al.
Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors
Clin Gastroenterol Hepatol
(2005)

L.S. Lee et al.

EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictors

Clin Gastroenterol Hepatol

(2005)

C. Fernández-del Castillo et al.

Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients

Arch Surg

(2003)

Cited by (66)

Efficacy and safety of EUS-guided through-the-needle microforceps biopsy sampling in categorizing the type of pancreatic cystic lesions
2022, Gastrointestinal Endoscopy
EUS-guided through-the-needle biopsy sampling (EUS-TTNB) using microbiopsy forceps is performed for the accurate diagnosis of pancreatic cystic lesions (PCLs). However, there are no standardized protocols for this procedure, and the amount of data on its efficacy is limited. Here, we evaluated the feasibility, efficacy, and safety of EUS-TTNB in categorizing the types of PCLs and identified the factors associated with diagnostic failure.
The prospectively collected and maintained EUS-TTNB database at Asan Medical Center was reviewed to identify patients with PCLs who underwent EUS-TTNB between January 2019 and January 2021. The primary outcomes were technical success, diagnostic yield, and adverse events. Factors contributing to diagnostic failure and the discrepancies in the diagnosis made by conventional modalities (ie, EUS morphology, cross-sectional imaging, and cystic fluid analysis) were also evaluated.
Forty-five patients were analyzed. EUS-TTNB was successfully performed in all patients (technical success, 100%). Histologic diagnosis of PCLs was made in 37 patients (diagnostic yield, 82%). When comparing EUS-TTNB with a presumptive diagnosis, EUS-TTNB changed the diagnosis in 10 patients in terms of the categorization of the types of PCLs. The diagnostic yield was significantly higher in those who had 4 or more visible biopsy specimens per session (93%) than in those with fewer than 4 visible biopsy specimens per session (67%; P = .045). During follow-up, 3 patients (7%) experienced adverse events (2 acute pancreatitis, 1 intracystic bleeding), and no life-threatening adverse event occurred.
EUS-TTNB showed high technical feasibility, diagnostic yield, and good safety profile. EUS-TTNB may improve the categorization of the types of PCLs. Studies with standardized procedure protocols are needed to reduce the diagnostic failure for the types of PCLs.
Reply
2021, Gastroenterology
Complication incidence of EUS-guided pancreas biopsy: A systematic review and meta-analysis of 11 thousand population from 78 cohort studies
2020, Asian Journal of Surgery
A systematic review and meta-analysis were performed to estimate the incidence of possible complications following EUS-guided pancreas biopsy. Pancreatic cancer has a very poor prognosis with a high fatality rate. Early diagnosis is important to improve the prognosis of pancreatic cancer. We searched Pubmed, Embase, Web of Science, and Scopus databases for studies published from inception to Augest, 2018. Meta-analysis were conducted with random-effect models and heterogeneity was calculated with the Q, I² and τ² statistics. We enrolled 78 studies from 71 articles in the meta-analysis, comprising 11,652 patients. Pooled data showed that the whole complication incidences were low 0.210 × 10⁻⁴(95%CI -0.648 × 10⁻⁴, 1.068 × 10⁻⁴). And they were in bleeding 0.002 × 10⁻⁴ (95%CI -0.092 × 10⁻⁴, 0.097 × 10⁻⁴), pancreatitis 0.002 (95%CI -0.082 × 10⁻⁴, 0.086 × 10⁻⁴), abdominal pain 0 (95%CI -0.037 × 10⁻⁴, 0.038 × 10⁻⁴), fever 0 (95%CI -0.032 × 10⁻⁴, 0. 032 × 10⁻⁴), infection 0 (95%CI -0.030 × 10⁻⁴, 0.031 × 10⁻⁴), duodenal perforation 0 (95%CI -0.033 × 10⁻⁴, 0.034 × 10⁻⁴), pancreatic fistula 0 (95%CI -0.029 × 10⁻⁴, 0.029 × 10⁻⁴), abscess 0 (95%CI -0.029 × 10⁻⁴, 0.029 × 10⁻⁴) and sepsis 0 (95%CI -0.029 × 10⁻⁴, 0.030 × 10⁻⁴). Subgroup analysis based on the tumor size, site, needle type and tumor style also showed robust results. The pooled data showed EUS-guided pancreas biopsy could be a safe approach for the diagnosis of pancreatic lesions. More large-scale studies will be necessary to confirm the findings across different population.
Histologic Analysis of Endoscopic Ultrasound-Guided Through the Needle Microforceps Biopsies Accurately Identifies Mucinous Pancreas Cysts
2019, Clinical Gastroenterology and Hepatology
Citation Excerpt :
Even the use of a ProCore FNA needle has resulted in a marginal increase in tissue acquisition, particularly for PCLs without any solid component.29 A cytology brush had been studied previously with mixed results, but this practice has been tempered by high rates of technical failure and adverse events.30 In the present study, TTNB of PCLs was performed successfully in nearly all (97.4%) of the 114 cases.
It is a challenge to accurately assess pancreatic cystic lesions (PCLs) and determine their risk. We compared the yield of tissue acquired with endoscopic ultrasound (EUS)-guided microforceps (through the needle tissue biopsy [TTNB]) with that of samples collected by EUS-guided fine-needle-aspiration (EUS-FNA), and the accuracy of analyses of each sample type in the diagnosis of mucinous PCLs.
We performed a prospective open-label study of 114 consecutive adults (56.1% women; mean age, 64.2 y) undergoing EUS-FNA evaluation of PCLs (mean size, 35 mm) at 7 centers, from June 20, 2016, through August 31, 2018. Samples were collected from each cyst by FNA and microforceps; samples collected by FNA were analyzed by cytology and samples collected by TTNB were analyzed by histology. Acquisition yield was defined as the percentage of specimens collected that were adequate for cytologic or histologic analysis. Diagnoses of mucinous cysts were made based on identification of pancreatic mucinous epithelium by cytology analysis of FNA samples or histologic analysis of TTNB samples. Surgical specimens were used as the reference standard when available.
The EUS-guided microforceps were successfully inserted into 97.4% (111 of 114) of PCLs. Tissue acquisition yield was significantly higher with TTNB (95 of 114; 83.3%) than FNA (43 of 114; 37.7%) (P < .001). Sixty-one PCLs were determined to be mucinous based on TTNB analysis (53.5%) vs 11 with FNA analysis (9.6%) (P < .001). Among PCLs categorized as equivocal, based on the level of carcinoembryonic antigen, TTNB analysis found 50% (41 of 82) to be mucinous and FNA analysis found 8.5% (7 of 82) to be mucinous (P < .001). Findings from analyses of samples collected by TTNB were 100% concordant with findings from histologic analysis of surgical specimens (14 of 14), whereas only 3 of 14 findings from analysis of samples collected by FNA were in agreement with findings from surgical specimens (21.4%) (P < .001). Four of 5 mucinous PCLs with advanced neoplasia (80%) were detected with TTNB compared with none with FNA (P = .04). Self-limited intracystic bleeding occurred in 7 patients (6.1%), and acute pancreatitis in 6 patients (5.3%).
In a multicenter prospective study of patients undergoing EUS-FNA for evaluation of PCLs, we found TTNB collection of tissues for histologic analysis to be safe and feasible, with an acquisition yield of 83.3%. Histologic analysis of samples collected by TTNB identified a larger proportion of mucinous PCLs compared with cytologic analysis of samples collected by FNA—even among samples categorized as equivocal, based on the level of carcinoembryonic antigen. More samples collected by TTNB than FNA were found to have advanced neoplasia. Clinicaltrials.gov no: NCT02979509.
Tissue acquisition in pancreatic cystic lesions
2019, Digestive and Liver Disease
Citation Excerpt :
After this, in 2010, three articles on brushing techniques in PCLs were published [23–25]. In the study by Sendino et al. [23], very different results with respect to cytology with EUS-FNA were obtained, with a 73% diagnostic adequacy vs 36%; moreover, with this technique, 50% of mucinous cells vs 18% of EUS-FNA were identified. Al-Haddad et al. [24] reported that brushing is more likely to provide an adequate mucinous epithelium specimen (62%) than standard FNA (23%), with an 8% rate of adverse events.
Despite the progress achieved by scientific research in recent years, pancreatic cystic lesions (PCLs) remain a challenging clinical problem. A significant percentage of benign PCLs are still wrongly sent to surgery, with all the related risks of a high number of surgery-related complications and mortality. Diagnosis of the type of PCL, and risk stratification for malignancy are essential for a correct management of these lesions. Several guidelines have identified some clinical and morphological aspects suggesting the need for more accurate exams. Endoscopic ultrasound fine needle aspiration (EUS-FNA) of cystic fluid for cytology is the advised method of tissue acquisition in several guidelines, and the most used technique around the world. However sensitivity and adequacy of this technique are limited by the low amount of cells dispersed in cystic fluid. Alternative techniques have been tested to target the cystic walls in an attempt to obtain microhistologic specimens in order to augment the probability of obtaining an adequate diagnostic sample.
The aim of this review is to offer a critical overview of the existing literature on tissue acquisition in PCLs, and emphasize advantages and disadvantages of each technique, and unclear areas that need to be investigated with future research.
The Use of Biomarkers in the Risk Stratification of Cystic Neoplasms
2018, Gastrointestinal Endoscopy Clinics of North America
Citation Excerpt :
Yield is increased if the needle is moved back and forth repeatedly.24 Other techniques proposed to increase diagnostic yield include use of the Moray microforceps and cytology brushes.25,26 Despite a high specificity of 93%, the potential miscategorization of cysts as nonmucinous limits the utility of cytology.27

View all citing articles on Scopus

View full text

Liver, Pancreas and Biliary TractEndoscopic ultrasonography-guided brushing increases cellular diagnosis of pancreatic cysts: A prospective study

Abstract

Background

Aim

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Conflict of interest

Dig Liver Dis

Gastrointest Endosc

Am J Gastroenterol

Gastrointest Endosc

Gastroenterology

Clin Gastroenterol Hepatol

Am J Gastroenterol

Gastrointest Endosc

Gastroenterology

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients

Arch Surg

Liver, Pancreas and Biliary Tract
Endoscopic ultrasonography-guided brushing increases cellular diagnosis of pancreatic cysts: A prospective study