Endoscopic ultrasound-guided through-the-needle biopsy for the diagnosis of cystic tumors of the pancreas: not for all patients

The increasing incidence of pancreatic cystic lesions (PCLs) represents a major problem in Western countries [1] [2]. First of all, we have to accurately establish in a minimally invasive fashion the diagnosis of the nature of the cyst. Noninvasive imaging techniques like computed tomography scanning or magnetic resonance imaging are not able to differentiate the type of tumor in a significant proportion of patients [2]. Furthermore, establishing a diagnosis of malignant or benign disease may be impossible in the early stages. Unfortunately, endoscopic ultrasound (EUS) image criteria, as well as EUS-guided fine-needle aspiration (EUS-FNA) of the cyst content for analysis, have been revealed to be suboptimal [2]. Most samples obtained from PCLs are poorly cellular and, despite advances in tumor markers (glucose, amylase, carcinoembryonic antigen [CEA], K-Ras, G-NAS, among others), fluid analysis is not able to provide a definitive diagnosis in a significant proportion of patients [2]. In recent years, some improvements to solve this problem have been introduced, such as EUS-guided laser confocal endomicroscopy for the characterization of the cyst wall, with promising results for the differentiation of serous and mucinous type PCLs [3]. However, the high cost of this type of device is likely to preclude its widespread use in clinical practice in the coming years.

In the search for more practical solutions, technical improvements have made possible a miniaturized biopsy forceps (Moray Microforceps; US Endoscopy, Mentor, Ohio, USA) that fits through a 19-gauge EUS-FNA cytology needle and can obtain biopsies from the inner part of the wall of the PCL, helping to establish a definitive tissue diagnosis [4]. A number of studies have shown this technique, named EUS-guided through-the-needle biopsy (TTNB), to be technically feasible from the duodenum and the stomach in 97.4 % of cases, with a tissue acquisition rate (83.3 %) that is significantly superior to EUS-FNA (37.7 %; P < 0.001) [5].

“...although EUS-guided TTNB may be useful in certain clinical scenarios, the wise use of this type of needle is mandatory, especially in those patients with a higher likelihood of developing a serious AE.”

Although initial retrospective studies supported an improved safety profile for this new EUS-TTNB technique, more recent reports with larger sample sizes, some of them prospective series, have highlighted a significant adverse event (AE) rate (12.3 %), with some of these AEs even causing death [5] [6]. When this type of AE occurs, one may either abandon the technique and investigate whether there is a safer one, or try to make improvements in the technique to help minimize risks. The latter was the aim of an initiative tested by Facciorusso et al. in the study published in the current issue of Endoscopy [7].

In this study, the authors investigated the largest cohort of patients who underwent EUS-TTNB for PCL diagnosis reported to date (n = 506). This large cohort of patients represents a significant experience with this technique at 10 institutions, which may potentially make these results more representative of clinical practice. The main objective of the study was to investigate the incidence of AEs after EUS-TTNB, to analyze any potential factors that may be associated with these AEs, and to try to correlate the likelihood of AEs with the identified risk factors. In this large retrospective multicenter cohort study, AEs were found in 58 of 506 patients with a PCL sampled by EUS-TTNB (11.5 %): 3 % were classified as moderate in severity, 1.8 % were severe, and 0.5 % (three patients) experienced a fatal AE. These concerning numbers of AEs were mostly associated with pancreatitis (29/506 patients; 5.7 %), fever/infection (10/506; 2 %), or intracystic bleeding (10/506; 2 %). Fatal AEs were all due to severe pancreatitis or septic shock that developed into uncorrectable multiorgan failure despite intensive care unit therapy.

The authors performed uni- and multivariate analysis and identified four risk factors that correlated with the likelihood of AEs: (i) patient age > or < 64 years old; (ii) number of passes (TTNB bites) > or < 2; (iii) complete aspiration of the cystic fluid; and (iv) diagnosis of an intraductal papillary mucinous neoplasm (IPMN). After complex statistical analysis, with testing and retesting of these factors by recursive partitioning analysis, the authors were able to establish three groups of patients according to their risk for AEs: (i) a high risk group – patients with an IPMN in whom more than two microforceps passes were performed – who had a risk of AEs as high as 28 % and were more likely to develop a fatal AE; (ii) a low risk group – patients aged < 64 with a diagnosis other than an IPMN who underwent complete aspiration of the cyst and tissue sampling in no more than microforceps passes; (iii) a medium risk group – those patients who did not fit the definition of either the high or low risk groups.

Although this is not the definitive answer to the PCL problem, these interesting findings and the resulting classification may be extremely useful in clinical practice. These results strongly support that EUS-TTNB should be avoided in patients who fit the high risk criteria. Furthermore, as samples obtained with the TTNB technique are small in size and usually several passes (TTNB bites) will be required to obtain an adequate tissue diagnosis [4], it seems reasonable to advocate that this technique is not used in IPMN patients.

This practical recommendation is open for discussion if one reviews other recent publications with more optimistic results [8]. The authors reported a series of 45 patients, most of them with an IPMN (49 %), in whom two or more TTNB bites had been obtained (median 4, range 1–7), with an AE rate of 7 % (mild pancreatitis and intracystic bleeding), all of which were mild, with no fatal or severe AEs reported [8]. The larger sample size of the Facciorusso study [7] and the precise analysis of factors that may help predict the appearance of AEs make it more reliable and we should take advantage of the information provided by the study.

Furthermore, although prospective comparative studies may help provide a definitive answer on this issue, it would be desirable to include recommendations in coming guidelines that support the cautious use of the EUS-TTNB device in PCL patients, but discourage the use of this device in patients that meet the high risk criteria and, in my opinion, this recommendation should extend to those patients where there is suspicion of an IPMN.

In summary, although EUS-guided TTNB may be useful in certain clinical scenarios, the wise use of this type of needle is mandatory, especially in those patients with a higher likelihood of developing a serious AE, as pointed out in the current study [7].

Publication History

Article published online:
04 August 2022

• References

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