Irving Levine, Arvind J Trindade

Abstract Endoscopic ultrasound tissue acquisition, in the form of both fine needle aspiration (EUS-FNA) and fine needle biopsy (EUS-FNB), is utilized for pancreatic mass lesions, subepithelial lesions, and lymph node biopsy. Both procedures are safe and yield high diagnostic value. Despite its high diagnostic yield, EUS-FNA has the potential limitations associated with cytological aspirations, including inability to determine histologic architecture, and perhaps small quantitative sample for further immunohistochemical staining. EUS-FNB, with its larger core biopsy needle, was designed to overcome these potential limitations. However, it remains unclear which technique should be used and for which lesions.Comparative trials are plagued by heterogeneity at every stage of comparison;including variable needles used, different definitions of endpoints, and therefore limits generalizability. Thus, we present a review of prospective trials, systematic reviews, and meta-analyses on studies examining EUS-FNA vs EUS-FNB.Prospective comparative trials of EUS-FNA vs EUS-FNB primarily focus on pancreatic mass lesions, and yield conflicting results in terms of demonstrating superiority of one method. Yet consistent among trials is potential for diagnosis with fewer passes, and larger quantity of sample achieved for next generation sequencing. Pertaining to subepithelial lesions and lymph node biopsy, fewer prospective trials exist, and larger prospective studies are necessary. Yet based on the available literature, we would recommend EUS-FNB for peri-hepatic lymph nodes.

Key Words: Endoscopic ultrasound fine-needle aspiration; Endoscopic ultrasound fine needle biopsy; Pancreatic lesions; Subepithelial lesions; Lymph node biopsy

INTRODUCTION

As medical and surgical therapeutics continue to evolve, there is a renewed emphasis on timely diagnosis of various illnesses. This mantra certainly holds true in gastrointestinal (GI) diseases, including pancreatic malignancies and GI tumors, where early and specific diagnosis guides management and impacts morbidity and mortality[1 ]. While cross sectional imaging can characterize lesions, a tissue diagnosis is often required for a definitive diagnosis prior to therapy[2 -5 ]. Endoscopic ultrasound tissue acquisition (EUS-TA) has improved the ability for tissue diagnosis in a minimally invasive technique. The two modalities for EUS-TA, endoscopic ultrasound fine needle aspiration (EUS-FNA) and endoscopic ultrasound fine needle biopsy (EUS-FNB) vary in technique and utility. Common indications for EUS-TA include the diagnosis and staging of pancreaticobiliary and luminal GI malignancy, and assessing lymphadenopathy associated with luminal GI and lung cancers[6 ]. Additionally, EUS-TA aids in evaluation of potentially neoplastic GI subepithelial lesions[6 ]. Comparative studies on the diagnostic ability of EUS-FNA and EUS-FNB has yielded conflicting results. Here we review prospective comparative data on EUS-FNAvsEUS-FNB for pancreatic masses, subepithelial lesions, and lymph node biopsy (Table 1 -3 ).

EUS-FNA

EUS-FNA was first introduced in 1992 . It is often combined with rapid onsite evaluation (ROSE) to improve diagnostic ability[7 ,8 ]. EUS-FNA is now standard of care for sampling pancreatic solid masses, subepithelial lesions, lymph nodes, among others. Current European Society of Gastroenterology and American Society of Gastroenterology recommend EUS-FNA as first line for diagnosing pancreatic lesions[9 -11 ].

Great variability exists in EUS-FNA equipment and technique. Several different needles size exist, with 19 G, 20 G, 22 G, and 25 G. Additionally, variability exists in aspiration technique, including the use of negative pressure suction (used with either a 5 mL or 10 mL syringe) or slow stylet pull. The aspirate from EUS-FNA is often sufficient for cytology and adequate for diagnosis, with diagnostic accuracy ranging from 77 %-95 % for pancreatic masses[9 ,10 ]. Given its minimally invasive technique and small needle size, EUS-FNA has low rates of morbidity[12 ].

However, several limitations exist for EUS-FNA which obtains a cytological specimen. EUS-FNA is limited by an inability to obtain histological architecture, and inability to perform immunohistochemical analysis and molecular profiling. This is of particular importance as certain neoplasms, such as stromal cell tumors and lymphomas, may be difficult to diagnose without histologic samples, as their tissue architecture and morphology are essential for accurate pathologic assessment and histochemical studies[9 ,13 -17 ]. Furthermore, with the increased attention on personalized or precision medicine in oncology, sufficient tissue sample to perform next generation sequencing is required. Current National Comprehensive Cancer Network guidelines recommend germline testing for any patient with confirmed pancreatic cancer using comprehensive gene panels for hereditary cancer syndromes, as well astumor/somatic gene profiling for patients with locally advanced or metastatic disease to identify mutations that may benefit from anti-cancer therapy. Testing on tumor tissue is preferred, however cell-free DNA testing can also be considered[18 ]. There remains uncertainty if EUS-FNA will be able to routinely provide adequate material for these studies[6 ].

Table 1 Prospective comparative trials regarding endoscopic ultrasound fine-needle aspiration vs fine needle biopsy for solid pancreatic mass lesions

EUS-FNB

In an attempt to overcome the limitations of EUS-FNA, EUS-FNB was first introduced in early 2000 s to obtain tissue specimens as opposed to aspiration-based cytology.With the goal of evaluating tissue core, EUS-FNB provided novel needles for improved diagnostic accuracy.

Table 2 Prospective comparative trials regarding endoscopic ultrasound fine-needle aspiration vs fine needle biopsy for subepithelial lesions

Table 3 Prospective comparative trials regarding endoscopic ultrasound fine-needle aspiration vs fine needle biopsy for lymph node biopsy

Early models of EUS-FNB utilized Trucut needle biopsy, with a tissue penetrating stylet within an outer cannula. The 19 G Trucut FNB proved more accurate than EUSFNA for diagnosing lymphomas and stromal tumors, but was limited by mechanical failure when attempting to biopsy pancreatic head masses and duodenal lesions due to the torqued echoendoscope and mechanical friction[16 ,19 ]. Newer models, including EchoTip HD ProCoreTM(Wilson-Cook Medical Inc., Winston-Salem, NC, United States)is available in 19 -25 G, and provides two cutting surfaces, a tip and reverse bevel, to further preserve histological architecture[1 ]. The reverse or opposing cutting bevel design of EUS-FNB needle allows for the biopsy of core histopathologic tissue. This aspect has the potential advantage of improving diagnostic performances, but also allowing a wide arrange of follow up testing[20 ]. Immunohistochemistry, which is required for the diagnosis of autoimmune pancreatitis, lymphoma, and metastasis, can be performed on the tissue core. Furthermore, molecular analysis, which is now standard of care for pancreatic malignancies, can be performed as well. Other needles,including SharkCoreTM(Medtronic Inc., Sunyvale, CA, United States) and AcquireTM(Boston Scientific, Malborough, MA, United States), (Figure 1 ) may achieve even higher diagnostic accuracy[21 ,22 ].

Figure 1 Fine needle biopsy needles.

Studies have demonstrated the high diagnostic yields of core specimen with EUSFNB with fewer needle passes[23 -25 ]. The potential concern when using EUS-FNB for increased bleeding is offset by the fewer passes required for diagnosis.

EUS-FNA VS EUS-FNB: OVERVIEW

Several comparative trials have evaluated EUS-FNAvsEUS-FNB. Interpreting the conflicting data is challenging, as trials are plagued by heterogeneity in every stage of comparison. Reported outcomes as well as definition of those outcomes vary between studies. For example, inconsistent use of the term “diagnostic accuracy” and“diagnostic adequacy” creates confusion. Furthermore, heterogeneity exists within equipment use (needle size), technique (suctionvsslow pull; specified number of passes). Additionally, designing strong randomized trials is limited by inability to blind endosonographers, and sometimes cytopathologists, to type of needle used[26 -57 ].

CONCLUSION

Endoscopic ultrasound tissue acquisition is routinely utilized in the evaluation of pancreatic mass lesions, subepithelial lesions, and lymph node biopsies. Ongoing confusions surrounds the ideal modality for EUS-TA, whether by EUS-FNA or EUSFNB. While more robust comparative clinical trials exist for pancreatic lesions compared to subepithelial lesions and lymph nodes, the data continues to be mixed.Randomized controlled trials with homogenous populations and homogenous sampling protocols are needed in order to truly understand which needle is superior.

Based on the literature reviewed in this paper, the authors conclude the following:EUS-FNA and EUS-FNB both provide high diagnostic accuracy, with low technical failure and adverse events, and thus either needle can be utilized for EUS-TA of pancreatic lesions, subepithelial lesions, and lymph nodes. In our experience we prefer FNB with a new generation needle as it allows us fewer passes of the needle, allows us to forgo ROSE which adds significant time and resource to a procedure, and gives a sample suitable for molecular testing. When increased quantity of DNA is desired for next generation sequencing, consider utilizing EUS-FNB. For extramural subepithelial lesions, consider utilizing EUS-FNB. Despite the dearth of prospective literature, we would recommend EUS-FNB for lymph node biopsy, specifically for peri-hepatic nodes.