Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: Final results from a large prospective multicenter study

doi:10.1016/j.dld.2013.08.134

Digestive and Liver Disease

Volume 46, Issue 1, January 2014, Pages 41-44

https://doi.org/10.1016/j.dld.2013.08.134 Get rights and content

Abstract

Background

Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been reported to have a higher complication rate than that of solid lesions, but the real complication rate is unknown. Aim of the study was to identify the complication rate of endoscopic ultrasound-guided fine needle aspiration and related risk factors.

Methods

Prospective multicenter study at four referral centres. Data were collected from January 2010 to July 2012, searching for all adverse events related to guided fine needle aspiration. All complications occurring up to day 90 were recorded.

Results

298 patients (43.9% male, mean age 63.2 ± 15.4 years) underwent endoscopic ultrasound-guided needle aspiration of pancreatic cystic lesions. Mean size was 34.1 ± 9 mm. Adverse events occurred in 18 patients (6%): mild complications in 12/18 (66.6%), and moderate complications in 6/18 (33.3%). Seven were immediate, 6 early, and 5 late. All resolved with medical therapy.

Conclusions

Endoscopic ultrasound-guided fine needle aspiration of pancreatic cystic lesions has been found to be associated with a higher complication rate than for solid lesions; however, the risk rate is acceptable considering the complication grade and the important diagnostic role of the technique in the management of pancreatic cystic lesions.

Introduction

Pancreatic cystic lesions (PCLs) are being diagnosed with increasing frequency, and cover a vast spectrum, from benign to malignant and invasive. Numerous investigations can be carried out to discriminate between benign and non-evolutive lesions and those that require surgery because there is no single test that allows for a correct diagnosis in all cases. Cystic fluid analysis and cytohistology with endoscopic ultrasound-guided fine needle aspiration (EUS FNA) can aid in this difficult diagnosis. In PCLs, EUS FNA allows evaluation of extracellular mucin, cytological and sometimes histological analysis, biochemical tests, tumour markers, and molecular analysis [1]. The EUS FNA techniques for pancreatic cystic lesions are quite simple. The needles normally used are the same as those for solid lesions, 19-, 22-, and 25-gauge. Doppler is recommended to avoid puncture of the intervening vessels, as is crossing the normal pancreatic parenchyma as little as possible to help avoid pancreatitis. Other recommendations include complete drainage of the cyst in a single needle passage, and antibiotic prophylaxis with intravenous antibiotics just before the procedure, followed by the oral route for 3–5 days to reduce the risk of infection (recommendation grade C) [2]. EUS FNA of cystic lesions has been reported to have a higher complication rate than that of solid lesions [2], [3], [4], [5], [6], [7], [8]. The incidence of infectious complications in prospective studies that used prophylaxis was low (0–1.4%) [3], [4], [5]. No data from controlled studies are available on complications, such as bleeding and pancreatitis, related to EUS FNA of cystic lesions. Finally, the risk of seeding after EUS FNA of malignant PCLs appears to be very low, with only one published case of peritoneal seeding after EUS FNA of a PCL [9]. Because of the higher expected rate of complications after puncture of PCLs than that of solid lesions, many centres prefer not to perform the procedure, renounce valuable information for diagnosis. A prospective study by the Mayo Clinic group on complications related to EUS FNA has been published. To our knowledge, this was the first prospective report, but the limitations of the study were that the complication rate was assessed at a single centre, and the number of EUS FNA procedures on PCLs was low [10]. The aim of our present study was to identify, in a large prospective multicenter study, the rate of adverse events of EUS FNA of PCLs, and the risks related to these complications.

Section snippets

Patients and methods

This was a prospective clinical study at four referral centres for EUS: ISMETT/UPMC (Mediterranean Institute for Transplantation and Advanced Specialized Therapies/University of Pittsburgh Medical Center in Italy), Palermo; AUSL Bologna Bellaria-Maggiore Hospital; Civico-A.R.N.A.S. Hospital, Palermo; Humanitas IRCCS, Rozzano, Milan. We collected data from January 2010 to July 2012 looking for all adverse events related to EUS FNA of PCLs. The procedures were carried out by one or two attending

Results

From January 2010 to July 2012, 298 patients (131 male [44%],), with a mean age of 63.2 years (SD ± 15.4), underwent EUS FNA of PCLs. The mean size of the PCLs was 34.1 mm (SD ± 19 mm). All patients completed the scheduled antibiotic prophylaxis as described in Section 2. Procedures were performed with patients under conscious sedation in 100 of cases (33.6%), deep sedation in 192 (64.4%), and general anaesthesia in 6 (2%). The needles used were: 22-gauge in 199 (66.8%) cases, 25-gauge in 22 (7.4%),

Discussion

This large, prospective, multicenter study shows the actual rate of adverse events after EUS FNA on PCLs. Complete follow-up data were obtained in 100% of the enrolled patients. We encountered only one complication related to conscious sedation (desaturation), which required the use of reversal agents. This low rate may be the result of two factors: appropriate selection of patients to be treated with deep and conscious sedation, and the constant presence of an anaesthesiologist in the case of

Conflict of interest statement

The authors declare no conflict of interest.

Acknowledgement

The authors thank Warren Blumberg for his editorial assistance.

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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.
Antibiotic Prophylaxis Is Not Required for Endoscopic Ultrasonography-Guided Fine-Needle Aspiration of Pancreatic Cystic Lesions, Based on a Randomized Trial
2020, Gastroenterology
Citation Excerpt :
Two recent prospective studies aimed at investigating the complications of EUS-FNA in this group of patients reported only 3 and 4 patients with suspicion of cyst infection, which resulted in 4.1% and 1.3% of the total series. Moreover, infection was not confirmed in any case, and all cases were resolved with antibiotic therapy.16,17 Our study confirms this low incidence because no pancreatic cyst infection occurred in 226 procedures, and only 1 infectious complication was observed in a patient with concurrent previous and postprocedural acute pancreatitis.
Guidelines recommend routine antibiotic prophylaxis for patients undergoing endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic cysts, but there is conflicting evidence for its necessity. We investigated whether performing the procedure without antimicrobial prophylaxis increases the incidence of infection.
We performed a multicenter, randomized, noninferiority trial to compare prophylaxis with ciprofloxacin vs placebo in patients with a pancreatic cyst requiring EUS-FNA at multiple centers in Spain. From September 2014 to June 2018, patients were randomly assigned to groups that received the prophylaxis with ciprofloxacin (n = 112) or saline solution (n = 114, placebo). We recorded patients’ demographic data, lesion characteristics, and procedure data and followed patients for 21 days. A total of 205 patients completed the trial (90.7%), receiving ciprofloxacin or the control, with no statistically significant differences in demographics, baseline data, or procedure characteristics between groups. The primary outcome was FNA-related infection. Secondary outcomes were incidence of fever, procedure complications, and medication-related adverse events.
The only case of FNA-related infection (0.44%) occurred in a patient in the placebo group (0.87%); this patient developed acute pancreatitis and bacteremia after the procedure. Prevention of infection was not inferior in the control group; the difference between proportions was 0.87% (95% confidence interval, –0.84% to 2.59%). There were no differences between groups in fever (2 patients in each group: 1.78% vs 1.76%; P = 1.00) or other adverse events.
In a randomized trial of patients undergoing EUS-FNA for pancreatic cyst evaluation, we found the risk of infection to be low. The incidence of infections did not differ significantly with vs without ciprofloxacin prophylaxis. (ClinicalTrials.gov, Number: NCT02261896).
Statins decrease the risk of acute pancreatitis after endoscopic ultrasound fine-needle aspiration of pancreatic cysts
2020, Hepatobiliary and Pancreatic Diseases International
Basic and clinical studies suggest that statins may prevent and even ameliorate acute pancreatitis. The present study was to evaluate whether statin decreases the risk of acute pancreatitis in patients undergoing endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts.
Out of 456 patients with pancreatic cysts referred to our center between 2006 and 2018, 365 were finally included in analyses: 86 were treated with statins and 279 were not at the time of endoscopic ultrasound fine-needle aspiration. We compared the acute pancreatitis incidence between the two groups, and we also compared other complications such as bleeding and infections.
Median age was 64 years [interquartile range (IQR) 62–69] and median cyst size was 24 mm (IQR, 21–29). The most frequent histology was intraductal papillary mucinous neoplasm (45.3% and 42.3% in the two groups, respectively; P = 0.98). All 13 patients experiencing post-endoscopic ultrasound acute pancreatitis were from the control group (4.7%), of which 3 were classified as severe pancreatitis. None of statin users developed post-procedural acute pancreatitis (odds ratio: 0.15; 95% confidence interval: 0.03–0.98; P = 0.03). No difference was registered with regard to severe pancreatitis and other complications.
Statins exert a beneficial role in preventing acute pancreatitis in patients with pancreatic cysts undergoing endoscopic ultrasound-guided fine-needle aspiration. If confirmed in prospective trials, our findings may pave the way to an extensive use of statins as prophylactic agents in pancreatic interventional endoscopy.
Association between macroscopically visible tissue samples and diagnostic accuracy of EUS-guided through-the-needle microforceps biopsy sampling of pancreatic cystic lesions
2019, Gastrointestinal Endoscopy
EUS-guided through-the-needle biopsy (TTNB) sampling has been reported to improve diagnostic yield compared with cytology for the evaluation of pancreatic cystic lesions (PCLs). The number of macroscopically visible tissue samples needed to reach an adequate diagnosis is still unknown.
This is a retrospective, single-center study on consecutive patients with PCLs with risk features (cyst >3 cm, thickened wall, cyst growth during follow-up, and mural nodules) who underwent TTNB sampling. The capability of differentiating mucinous versus nonmucinous cysts, ability to obtain a cyst-lining epithelium, definition of the grade of dysplasia, and specific diagnosis of cyst histotype were evaluated for 1, 2, or 3 TTNB macroscopically visible specimens.
Sixty-one patients were evaluated. A 100% histologic adequacy was reached by 2 samples (P = .05 versus 1). Compared with cytology, 1 TTNB specimen improved the possibility of defining cyst histotype (P < .0001), whereas 2 specimens increased all 4 diagnostic categories (P < .003). Two specimens also increased diagnostic yield compared with 1 sample (P < .085). The collection of a third sample did not improve the value of any diagnostic categories. A specific diagnosis was reached in 74% of patients with 2 histologic samples. The diagnostic reliability of TTNB sampling compared with surgical histology was 90%, with a 22.9% rate of adverse events.
Two TTNB macroscopically visible specimens reached 100% histologic adequacy and a specific diagnosis in 74% of patients. The collection of a third specimen did not add any additional information and should be avoided to possibly decrease the risk of adverse events.
Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions
2019, Gastrointestinal Endoscopy
The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples.
TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet’s AC1 was used to assess interobserver agreement.
An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95).
Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.
Tissue acquisition in pancreatic cystic lesions
2019, Digestive and Liver Disease
Citation Excerpt :
However, all adverse events were considered mild because they resolved spontaneously without any treatment. Intracystic hemorrhage is relatively common even when performing a standard FNA in PCLs and, to date, only one case requiring transfusion has been reported [41]. Future studies are needed to verify whether this complication could have a clinical significance or has to be considered simply a side-effect of EUS-TTNB in PCLs.
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.

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Digestive EndoscopyComplications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: Final results from a large prospective multicenter study

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Conflict of interest statement

Acknowledgement

Gastroenterology Clinics of North America

Pancreatology

Gastroenterology

Gastrointestinal Endoscopy

Clinical Gastroenterology and Hepatology

Gastrointestinal Endoscopy

Gastrointestinal Endoscopy

Digestive Endoscopy
Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: Final results from a large prospective multicenter study