Second-generation fine-needle biopsy for autoimmune pancreatitis: ready for prime time?

Autoimmune pancreatitis (AIP) is a rare disease. According to the International Consensus Diagnostic Criteria (ICDC) [1], two types of AIP are identified: (i) type 1 AIP (80 % of AIPs), called lymphoplasmacytic sclerosing pancreatitis (LPSP), which is the pancreatic manifestation of a systemic disease called IgG4-related disease and usually affects men over 60 years of age, most often being accompanied by jaundice or severe cholestasis (60 % – 80 %), with little or no pain; (ii) type 2 AIP (20 % of AIPs), called idiopathic duct-centric pancreatitis (IDCP), which affects both women and men between 30 and 45 years of age, is often painful, with acute or mild subacute pancreatitis, but rarely with jaundice (15 %), and is associated with inflammatory bowel disease in 20 % of cases. The treatment of AIP is not a real issue as symptoms respond to corticosteroid therapy in almost all cases.

“The most interesting result of the study is the direct correlation between the length of specimens obtained and the detection rate of the four histological criteria for type 1 AIP (80 % of AIPs).”

In contrast, the diagnosis of AIP remains challenging as half of AIP cases present as focal resectable masses using cross-sectional imaging, which can lead to unnecessary pancreatic resection for a presumed cancer. On the other hand, a false-positive diagnosis of AIP can lead to the wrong treatment with steroids or adoption of an erroneous “wait and see strategy” in cases of a true pancreatic cancer. Histology is crucial for the diagnosis of definitive type 1 AIP in at least 25 % of the cases where the serum level of IgG4 is normal and in most cases of type 2 AIP.

Results of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) in patients with AIP have been published over many years. With the exception of two studies published by the same team in 2012 and 2016 [2] [3], there are no satisfactory results using 22G needles and slightly better, but still insufficient, results with 19G needles. For that reason, EUS-guided FNA was not considered in the 2011 International Consensus.

Recently, three second-generation FNB “cutting” needles have become available, two of which are 22G needles (Franseen tip and fork tip) and one of which is a 20G forward-bevel needle. These needles have demonstrated significantly better results than standard EUS-FNA needles and first-generation EUS-FNB needles in obtaining core tissue specimens from pancreatic masses.

In the study published in this issue of Endoscopy [4], Ishikawa et al. rated the effectiveness of the Franseen needle to histologically diagnose AIP. It was a prospective multicenter study involving 56 patients who met the imaging ICDC for AIP: 51 were ultimately diagnosed with AIP (50 with definitive type 1 and one with probable type 2).

With regard to the primary end point of the study, the authors report a detection rate of 58.2 % for ICDC level 1 histology of type 1 AIP, which is a good result in comparison with those published using EUS-guided FNA. The most interesting result of the study is the direct correlation between the length of specimens obtained and the detection rate of the four histological criteria for LPSP. When the length was 20 mm or more, the level 1 histology rate was 85.7 %. However, this length was obtained in only 25.4 % of the samples. The consequence of this lack of sensitivity is that, among the 24 % of patients in this study who needed histological diagnosis, and therefore EUS-guided biopsy, only 46 % of them had level 1 histology but, thanks to the addition of level 2 histology, 62 % of them finally achieved a diagnosis of definitive type 1 AIP.

For the endosonographers facing a clinical suspicion of type 1 AIP, the question is: are these good results reproducible? The answer is “Yes” as, in a recently published randomized prospective study [5], comparing the first pass of the Franseen needle to the first pass of the 20G forward-bevel needle, Kurita et al. reported similar results to Ishikawa et al. for the detection rate of level 1 histology (56 % versus 58.2 %). However, in the study of Kurita et al., the results were not as good as those published here [4] for lymphoplasmacytic infiltration rate (84 % versus 100 %) and level 2 histology (22 % versus 34.5 %), leading to a lower rate of level 1 or 2 histology (78 % versus 92.7 %).

This leads to an additional question: would an appropriate sampling technique be able to improve the percentage of cases where the length of the specimen obtained is suitable for the histological diagnosis of definitive type 1 AIP? In my experience and in the literature published on the subject, it seems the answer is again “Yes.” The following three factors (in addition to the fanning method that is now widely used around the world) appear to play a critical role in achieving better histological results.

1. Speed of needle entry into the target. Studies that have used a spring-loaded biopsy needle that greatly accelerates the penetration speed (a system that is no longer available) [2] [6] or that have used as fast a motion of the needle into the target as possible [3] have obtained particularly interesting results for the diagnosis of AIP.

2. The slow-pull technique. This causes less fragmentation and dissociates fewer samples than the conventional suction technique, meaning this technique should be preferred for obtaining core tissue when sampling the pancreas with these new cutting needles.

3. The number of passes made. In this study [4], two passes were insufficient in 75 % of cases to obtain a total length of tissue fragments of more than 20 mm, the length that is required to obtain a histological diagnosis of definitive type 1 AIP. As a result, the number of supplementary passes should be adjusted to the length of the macroscopically visible cores, according to the macroscopic on-site evaluation (MOSE) of the two first passes [7].

In summary, the use of the Franseen needle significantly improves the performance of EUS-FNB for the diagnosis of type 1 AIP. However, an appropriate sampling technique should be used to further optimize the possibilities with this new cutting needle: make the fastest possible movement when penetrating the target, perform 10 – 20 movements this way, use the slow-pull technique in order to get an intact core sample, and make two to four passes, depending on MOSE results after the first two passes.

Finally, is the Franseen needle the best second-generation FNB needle to use when faced with a patient with a suspicion of AIP? We do not yet have the answer to that question. There has been no study involving the 22G fork-tip needle in AIP, although this needle has demonstrated results as good as those of the Franseen needle for the histological diagnosis of pancreatic cancers.

In conclusion, the use of the Franseen FNB needle improves the ability to histologically diagnose a definitive type 1 AIP, and this ability should be promoted in patients with suspected AIP requiring histological evidence. These results are not amazing and could, in my view, be improved by a better way to proceed with the needles. Large multicenter prospective randomized studies devoted to the subgroup of patients with suspected AIP requiring histological evidence, including type 2 AIP, and comparing all the second-generation FNB cutting needles are warranted.

Publication History

Article published online:
27 October 2020

• References

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• 3 Kanno A, Masamune A, Fujishima F. et al. Diagnosis of autoimmune pancreatitis by EUS-guided FNA using a 22-gauge needle: a prospective multicenter study. Gastrointest Endosc 2016; 84: 797-804
• 4 Ishikawa T, Kawashima H, Ohno E. et al. Usefulness of endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of autoimmune pancreatitis using a 22-gauge Franseen needle: a prospective multicenter study. Endoscopy 2020; 52: 978-985
• 5 Kurita A, Yasukawa S, Zen Y. et al. Comparison of a 22-gauge Franseen-tip needle with a 20-gauge forward-bevel needle for the diagnosis of type 1 autoimmune pancreatitis: a prospective, randomized, controlled, multicenter study (COMPAS study). Gastrointest Endosc 2020; 91: 373-381.e2
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• 7 Iwashita T, Yasuda I, Mukai T. et al. Macroscopic on-site quality evaluation of biopsy specimens to improve the diagnostic accuracy during EUS-guided FNA using a 19-gauge needle for solid lesions: a single- center prospective pilot study (MOSE study). Gastrointest Endosc 2015; 81: 177-185