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Through-the-needle microforceps biopsy: a powerful tool but for selected patientsReferring to Kovacevic B et al. p. 44–52
Pancreatic cystic lesions (PCLs) are a common incidental finding on cross-sectional imaging, with a prevalence of 13.5 % that increases with age . Despite very low progression to pancreatic cancer , the spectrum of pathology ranges from benign lesions to invasive neoplasms, and the possible threat of cancer is a looming fear for both patients and physicians. Endoscopic ultrasound (EUS) is indicated when clinical or radiological features of concern mean the lesion is considered for surgical resection or when the patient’s management dramatically changes according to the cyst histological subtype . However, cyst morphology is often non-specific and “traditional” cystic fluid analyses (i. e. carcinoembryonic antigen [CEA] and cytology) obtained through EUS-guided fine-needle aspiration (EUS-FNA) have low accuracy in differentiating mucinous vs. non-mucinous lesions, and in defining the nature of the cyst .
“TTNB could become a game-changer for the diagnostic evaluation of PCLs by providing useful information to guide the decision-making process and by reducing the rate of inappropriate surgery, which is often performed based on presumptive diagnoses.”
Recently, a microforceps that is able to pass through a 19G needle (Moray; US Endoscopy, Mentor, Ohio, USA) has become available. The main advantage of this device is the capability of retrieving histological specimens from the cystic wall, allowing the definition of the cyst histological subtype in approximately 75 % of cases . Despite outperforming the accuracy of EUS-FNA fluid cytology, the reported risks of intracystic bleeding and acute pancreatitis are about 6 % and 2.5 %, respectively , making accurate selection of patients vital to balance the risks and benefits of the procedure.
In this issue of Endoscopy, Kovacevic et al. report a prospective experience with through-the-needle biopsy (TTNB) in 101 patients with PCLs, in which both the clinical impact of TTNB (i. e. change in patient management) and the rate of adverse events were evaluated . TTNB changed the clinical management in approximately 12 % of cases (10 follow-up discontinuation and two mucinous cyst diagnoses), although with not a negligible rate of adverse events (9.9 %, including three severe and one fatal event).
Based on these results, the perception of TTNB use is that it is risky, with very limited clinical usefulness. However, in this study, the authors pushed the boundaries of the indications for EUS-FNA by including PCLs of ≥ 15 mm even in the absence of “worrisome features” . Moreover, 40 % of the cases showed multifocal disease that was highly suggestive of intraductal papillary mucinous neoplasm (IPMN), whose management is mainly based on morphological features. This allowed the rapid enrollment of a large number of patients (101 patients included out of 521 assessed for eligibility over 19 months), but at the expense of proper patient selection and, consequently, of the clinical impact. Indeed, it is likely that, in the majority of the cases included by Kovacevic et al. , TTNB confirmed the presumed diagnosis of IPMN but without impacting the patient’s management.
The strength of TTNB is the possibility of accurately defining the exact type of cyst. Therefore, TTNB is often decisive when the morphology of the cyst is non-specific, for example in patients with large unilocular/oligocystic PCLs without clear-cut communication with the pancreatic ducts, for whom management radically changes according to the cyst histological subtype, from surgical resection in the case of a mucinous cystic neoplasm  or cystic neuroendocrine tumor to discontinuation of follow-up in the case of a serous cystadenoma. In fact, in the study of Kovacevic et al. , in 10 out of 12 cases, TTNB changed the patient management by reaching a diagnosis of serous cystadenoma, thereby allowing discontinuation of follow-up. Of course, discontinuation of follow-up for benign cysts is a relevant point. However, it was not specified in how many cases TTNB avoided inappropriate surgery for these lesions.
Another point that deserves to be discussed is the possibility of IPMN subtyping on TTNB samples. The authors must be commended for demonstrating the feasibility of histopathological analysis on TTNB samples. It is known that the pancreaticobiliary subtype is more often associated with invasive carcinoma, whereas the gastric subtype is rarely associated with high grade dysplasia. Fortunately, the gastric subtype is the most common, with a prevalence of about 60 %, whereas the pancreaticobiliary subtype does not exceed 6 % . These data, however, come from surgical series and the prevalence of the gastric subtype in a non-resected population could be even higher. Therefore, even assuming that the accuracy of TTNB for IPMN subtyping is 100 %, we would need to be perform at least 100 TTNB procedures to identify six patients with the pancreaticobiliary subtype. Is this information worth the TTNB procedure, especially given the adverse event rate? Probably not in an unselected population, but it could be useful in a subgroup of patients to support the decision-making process (e. g. in high surgical risk patients with “worrisome” cysts but without clear signs of malignancy). Moreover, about 25 % of IPMNs contain more than one epithelial subtype  (most frequently a combination of gastric and pancreaticobiliary subtypes) or are unclassifiable, and sampling errors using the microforceps could occur, leading to misclassification. To date, the reliability of TTNB for IPMN subtyping compared with surgical pathology has not been evaluated.
The TTNB technique is not yet standardized and the associations between its technical aspects (e. g. the number of bites performed or specimens retrieved) and the rate of adverse events, as well as the impact of prophylactic measures, have not yet been fully evaluated. In the study of Kovacevic et al. , no predictive factors for adverse events were identified and no relationship between adverse events and procedural features, including procedure time, intracystic needle time, and the number of passes, was observed. Although all of the adverse events occurred in patients with IPMNs, a significant correlation could not be demonstrated (P = 0.19). Interestingly, the protocol was amended after 3 months of enrollment to add perioperative hydration with 1 L of Ringer lactate and the administration of rectal diclofenac 100 mg, which led to a reduction in the adverse event rate from 17.6 % to 8.3 %. Future studies should further investigate the impact of prophylactic measures commonly employed to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis on the rate of TTNB-related adverse events.
TTNB could become a game-changer for the diagnostic evaluation of PCLs by providing useful information to guide the decision-making process and by reducing the rate of inappropriate surgery, which is often performed based on presumptive diagnoses. However, TTNB is not for all PCLs. Multidisciplinary discussion and patient selection considering age and co-morbidities, morphology and risk features of the cyst, and the type of possible surgical intervention are essential before deciding to perform the procedure. When a definitive diagnosis is considered crucial for driving the patient’s management, TTNB should certainly be considered.
17 December 2020 (online)
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- 1 Lee KS, Sekhar A, Rofsky NM. et al. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol 2010; 105: 2079-2084
- 2 Gardner TB, Glass LM, Smith KD. et al. Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults. Am J Gastroenterol 2013; 108: 1546-1550
- 3 European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018; 67: 789-804
- 4 Crinò SF, Bernardoni L, Brozzi L. et al. Association between macroscopically visible tissue samples and diagnostic accuracy of EUS-guided through-the-needle microforceps biopsy sampling of pancreatic cystic lesions. Gastrointest Endosc 2019; 90: 933-943
- 5 Tacelli M, Celsa C, Magro B. et al. Diagnostic performance of endoscopic ultrasound through-the-needle microforceps biopsy of pancreatic cystic lesions: Systematic review with meta-analysis. Dig Endosc 2020; DOI: 10.1111/den.13626.
- 6 Kovacevic B, Klausen P, Vestrup Rift C. et al. Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts. Endoscopy 2020; 44-52
- 7 Crinò SF, Bernardoni L, Gabbrielli A. et al. Beyond pancreatic cyst epithelium: evidence of ovarian-like stroma in EUS-guided through-the-needle micro-forceps biopsy specimens. Am J Gastroenterol 2018; 113: 1059-1060
- 8 Schaberg KB, DiMaio MA, Longacre TA. Intraductal papillary mucinous neoplasms often contain epithelium from multiple subtypes and/or are unclassifiable. Am J Surg Pathol 2016; 40: 44-50