Endoscopic ultrasound-guided fine-needle biopsy: size really does matter!

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the gold standard for the diagnosis of pancreatic and peripancreatic masses, often achieving a sensitivity of 90 %, with a specificity of 100 % [1]. It is not clear whether the size of needle used matters, with a recent meta-analysis demonstrating similar sensitivity, specificity, and safety profiles for 22 G and 25 G FNA needles [2]. However, FNA needles are limited by: a high reliance on rapid on-site evaluation (ROSE); their lower yield in a highly desmoplastic stroma, often seen in pancreatic cancers; their inability to achieve histologic architecture; and often the obtaining of an insufficient quantity of tissue to allow genome profile analysis for targeted therapies to be performed [3]. Many of these limitations have been overcome with the development of newer “core needles” that obtain histologic and not just cytologic samples [4].

In this issue of Endoscopy, Oh et al. present the results of a randomized study comparing 25 G and 22 G Franseen-tip needles for EUS-guided fine-needle biopsy of pancreatic and peripancreatic masses [5]. The authors set up a non-inferiority trial to evaluate the differences between the two sizes of needle. A total of 70 patients were enrolled in each group and the non-inferiority margin between the two groups was set at −15 %. Histologic quality was determined by the Gerke score [6], which was evaluated by two independent pathologists blinded to the needle size. A Gerke score of 4 or 5 indicates a sample that enables high quality histologic assessment. Samples adequate for histologic assessment were obtained from 87.1 % of patients in the 25 G group and 97.1 % in the 22 G group, resulting in a −10 % difference. However, the 95 % confidence interval (−17.35 % to −2.65 %) exceeded the predetermined −15 % non-inferiority margin, meaning the 25 G needle was considered inferior compared with the 22 G needle in obtaining histologic cores.

“This is the first study to evaluate the histologic yields from two different sizes of Franseen-tip needles and to show higher quality histologic cores with the larger 22 G needle.”

Importantly, the authors also evaluated the sensitivity, specificity, and accuracy of malignancy detection by needle size. There was no difference in the sensitivity to detect malignancy between the 22 G needle (100 %) and the 25 G needle (98.4 %). In addition, slides were made for cytologic analysis from the core sample and these similarly showed no difference in sensitivity between the 22 G (96.8 %) and 25 G needles (95.1 %). Notably, there was no difference in the adverse events between the two sizes of needle and only one patient in the entire cohort had an adverse event (mild acute pancreatitis in one patient in the 22 G group).

This is the first study to evaluate the histologic yields from two different sizes of Franseen-tip needles and to show higher quality histologic cores with the larger 22 G needle. Previous studies with a fork-tip needle design have not demonstrated superiority for the 22 G needle compared with the 25 G needle [7]. Similarly, there was no difference in histologic yields between a 22 G Franseen-tip needle and a 22 G fork-tip needle [4]. How can we explain that the 25 G Franseen-tip needle is inferior here, when other studies have not shown a difference between the Franseen and fork-tip needles and no difference has been found between needle sizes when evaluating the fork-tip needles? It seems that variations in needle design are probably not solely responsible for the performance differences.

One explanation is that the prior fork-tip study was a retrospective comparison of consecutive patients, in contrast to the current randomized controlled study [5] [7]. In the current study, a non-inferiority design was employed, which is more commonly used for drug studies [8]. In a non-inferiority trial, the aim is to show that a new drug or device is not unacceptably worse than an older one. One reason non-inferiority trials are commonly used in drug studies is that a non-inferior new drug may have a more tolerable dosing regimen or fewer side-effects, which would make it more desirable. A strength of non-inferiority trials is that they do not suffer from multiple testing [8]. In the current study, for example, the authors can appropriately claim that the 22 G needle is superior in obtaining optimal histologic cores compared with the 25 G needle, given that the confidence interval did not include 0.

Could the differences be explained by how the quality of the histologic core was determined? The Gerke score was developed to evaluate EUS-guided Trucut biopsy samples and is not a commonly used histologic scoring system [6]. Certainly, the use of validated image software that could rate desmoplastic fibrosis, retained tissue architecture, and the total tissue area could serve to decrease subjectivity [4]. The authors do recognize this as a limitation and, given that two experienced pathologists blinded to the needle size reviewed their data, this is unlikely to account for any differences in the outcome.

How will I utilize the results of this study in my own practice? Though this study was not powered to evaluate the ability to detect malignancy by needle size, it is important to remember that there is no difference in the sensitivity to detect malignancy between the two needle sizes. Given this result, one may still consider a 25 G needle when sampling an uncinate process lesion from the second part of the duodenum, given the torqued scope and the need for the scope elevator. However, in lesions that require a true histologic core, such as autoimmune pancreatitis or lymphoma, or as there is increased need for a larger quantity of tissue for molecular analysis to aid with targeted therapy [3], a 22 G Franseen needle seems to be the logical choice rather than the 25 G Franseen needle.

Publication History

Article published online:
03 August 2021

• References

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