Clinical trial NCT04404101: Evaluation of Pancreatic Cystic Lesions Via EUS-guided Fine Needle Aspiration With and Without Micro Forceps Biopsies
Official title: Evaluation of Pancreatic Cystic Lesions Via EUS-Guided Fine Needle Aspiration With and Without Micro Forceps Biopsies: A Multi-Center Prospective Randomized Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreatic Cyst
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: US Endoscopy
First posted: 2020-05-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Pancreatic cystic lesions (PCLs) are a common incidental finding in cross sectional imaging (up to 27% on CT scan and 41% on MRI) and pose a management challenge to physicians. According to society guidelines, PCLs with specific features should prompt additional workup with endoscopic ultrasound (EUS) for cyst characterization as well as cyst sampling. This can help determine if the cyst is mucinous or non-mucinous which has implications for its malignant potential. Cyst fluid has traditionally been sampled using EUS with fine needle aspiration (EUS-FNA) and sent for fluid analysis and cytology. More recently, the adjunctive use of the through-the-scope micro forceps (Moray micro forceps, US Endoscopy, Mentor, OH) biopsy (EUS-MFB) has shown promise for diagnosis of PCLs. This technology utilizes a micro forceps through a 19-gauge needle to biopsy the cyst wall for histology, in addition to collecting cyst fluid for CEA level and cytology. More recently, the adjunctive use of the Moray® through the needle micro forceps biopsy (EUS-MFB) has shown promise for diagnosis of PCLs. This technology utilizes a micro forceps through a 19-gauge needle to biopsy the cyst wall for histology, in addition to collecting cyst fluid for CEA level and cytology. Only a few small retrospective reports have been published regarding the use of MFB. The results of this study will hopefully help increase diagnostic yield by obtaining a histopathologic diagnosis of these PCLs, and potentially affect practice patterns of gastroenterologists and the endoscopic community, specifically those physicians who perform EUS in these patients. Furthermore, the results will help determine whether there is reason to continue this line of research to obtain a definite histologic tissue diagnosis of PCLs.

Detailed description: Pancreatic cystic lesions (PCLs) are a common incidental finding in cross sectional imaging (up to 27% on CT scan and 41% on MRI) and pose a management challenge to physicians. According to society guidelines, PCLs with specific features should prompt additional workup with endoscopic ultrasound (EUS) for cyst characterization as well as cyst sampling. This can help determine if the cyst is mucinous or non-mucinous which has implications for its malignant potential. Cyst fluid has traditionally been sampled using EUS with FNA (Fine-Needle Aspiration) and sent for fluid analysis (CEA and amylase) and cytology. However, despite use of a cyst fluid carcinoembryonic antigen (CEA) level cutoff of 192 ng/mL and cytology, accuracy of diagnosis for PCLs is poor. As the spectrum ranges from benign to high risk for neoplasm, precise diagnosis is critical. More recently, the adjunctive use of the Moray® through the needle micro forceps biopsy (EUS-MFB) has shown promise for diagnosis of PCLs. This technology utilizes a micro forceps through a 19-gauge needle to biopsy the cyst wall for histology, in addition to collecting cyst fluid for CEA level and cytology. Only a few small retrospective reports have been published regarding the use of MFB. Pancreatic cysts continue to pose a management dilemma for practicing clinicians, especially with the increased use of radiologic imaging modalities identifying incidental pancreatic cystic lesions with higher frequency. This leads to patient anxiety and increased costs due to radiologic surveillance and even surgery. The results of this study will hopefully help increase diagnostic yield by obtaining a histopathologic diagnosis of these PCLs, and potentially affect practice patterns of gastroenterologists and the endoscopic community, specifically those physicians who perform EUS in these patients. Furthermore, the results will help determine whether there is reason to continue this line of research to obtain a definite histologic tissue diagnosis of PCLs.

Eligibility criteria: Inclusion Criteria:

* Adult patients \>18 years old
* Cysts \> 20 mm in size deemed appropriate for FNA by the endoscopist, based on clinical presentation, radiologic imaging features, associated solid mass or nodules, and patient anxiety about the diagnosis

Exclusion Criteria:

* Age \<18 years
* Inability to provide informed consent
* Thrombocytopenia (Platelets \< 50,000) or coagulopathy (INR \> 1.8)
* Pregnancy
* Post-surgical anatomy where the cyst is not accessible for FNA
* EUS findings suggesting that cyst FNA would be unsafe (e.g. intervening blood vessels)
* EUS appearance suggesting FNA is not indicated (e.g. cyst smaller than prior radiologic imaging, cyst not seen, EUS suggestive of serous cystadenoma)

Primary outcomes:
measure: Technical Success of EUS-FNA plus MFB, with EUS-FNA alone for evaluation of PCLs.
timeFrame: Intraprocedural
measure: Clinical Success of EUS-FNA plus MFB, with EUS-FNA alone for evaluation of PCLs.
timeFrame: 0-4 weeks
measure: Safety of EUS-FNA plus MFB with that of EUS-FNA by recording adverse events per published ASGE (American Society for Gastrointestinal Endoscopy) criteria.
timeFrame: 0-4 Weeks
Secondary outcomes:
measure: Technical ease in performing FNA and MFB
timeFrame: Intraprocedural
measure: Time taken for FNA and time for MFB
timeFrame: Intraprocedural
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado - Anschutz Medical Campus
state: Colorado
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: University of Colorado, Denver
name: Anna Duloy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moris M, Bridges MD, Pooley RA, Raimondo M, Woodward TA, Stauffer JA, Asbun HJ, Wallace MB. Association Between Advances in High-Resolution Cross-Section Imaging Technologies and Increase in Prevalence of Pancreatic Cysts From 2005 to 2014. Clin Gastroenterol Hepatol. 2016 Apr;14(4):585-593.e3. doi: 10.1016/j.cgh.2015.08.038. Epub 2015 Sep 11.
citation: Tanaka M, Fernandez-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012 May-Jun;12(3):183-97. doi: 10.1016/j.pan.2012.04.004. Epub 2012 Apr 16.
citation: Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015 Apr;148(4):819-22; quize12-3. doi: 10.1053/j.gastro.2015.01.015. No abstract available.
citation: Del Chiaro M, Verbeke C, Salvia R, Kloppel G, Werner J, McKay C, Friess H, Manfredi R, Van Cutsem E, Lohr M, Segersvard R; European Study Group on Cystic Tumours of the Pancreas. European experts consensus statement on cystic tumours of the pancreas. Dig Liver Dis. 2013 Sep;45(9):703-11. doi: 10.1016/j.dld.2013.01.010. Epub 2013 Feb 14.
citation: Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004 May;126(5):1330-6. doi: 10.1053/j.gastro.2004.02.013.
citation: Attili F, Pagliari D, Rimbas M, Inzani F, Brizi MG, Costamagna G, Larghi A. Endoscopic ultrasound-guided histological diagnosis of a mucinous non-neoplastic pancreatic cyst using a specially designed through-the-needle microforceps. Endoscopy. 2016;48 Suppl 1:E188-9. doi: 10.1055/s-0042-108194. Epub 2016 May 23. No abstract available.
citation: Mittal C, Obuch JC, Hammad H, Edmundowicz SA, Wani S, Shah RJ, Brauer BC, Attwell AR, Kaplan JB, Wagh MS. Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video). Gastrointest Endosc. 2018 May;87(5):1263-1269. doi: 10.1016/j.gie.2017.12.025. Epub 2018 Jan 6.
citation: Zhang ML, Arpin RN, Brugge WR, Forcione DG, Basar O, Pitman MB. Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts. Cancer Cytopathol. 2018 Jun;126(6):414-420. doi: 10.1002/cncy.21988. Epub 2018 Apr 16.
citation: Basar O, Yuksel O, Yang DJ, Samarasena J, Forcione D, DiMaio CJ, Wagh MS, Chang K, Casey B, Fernandez-Del Castillo C, Pitman MB, Brugge WR. Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts. Gastrointest Endosc. 2018 Jul;88(1):79-86. doi: 10.1016/j.gie.2018.02.039. Epub 2018 Mar 3.
citation: Barresi L, Crino SF, Fabbri C, Attili F, Poley JW, Carrara S, Tarantino I, Bernardoni L, Giovanelli S, Di Leo M, Manfrin E, Tacelli M, Bruno MJ, Traina M, Larghi A. Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A multicenter study. Dig Endosc. 2018 Nov;30(6):760-770. doi: 10.1111/den.13197. Epub 2018 Jul 5.
citation: Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, Mergener K, Nemcek A Jr, Petersen BT, Petrini JL, Pike IM, Rabeneck L, Romagnuolo J, Vargo JJ. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010 Mar;71(3):446-54. doi: 10.1016/j.gie.2009.10.027. No abstract available.