Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Adenocarcinoma

Cysts

Pancreatic Cyst

Mucocele

Pathological Conditions, Anatomical

Pancreatic Diseases

Gastrointestinal Diseases

Use of EUS-guided through-the-needle microbiopsy forceps for obtainment of tissue from the wall of the cystic lesion

EUS-guided microbiopsy

Prevalence of genetic mutations in known cancer-associated genes in the microbiopsy tissue examined using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, USA). The multigene panel explores selected regions of 50 cancer-associated genes, among others KRAS, GNAS, CDKN2A and SMAD4 genes.

Next Generation Sequencing

The purpose of this study is to determine clinical impact of EUS-guided microbiopsy procedure and supplementary molecular analyses compared to standard diagnostic workup of pancreatic cysts. The hypothesis is that a combination of previously mentioned modalities may change the management of some pancreatic cystic lesions, increase the diagnostic accuracy and optimize the discrimination between high- and low-risk pancreatic cysts.

Pancreatic ductal adenocarcinoma (PDAC) accounts for 6% of all cancer related deaths in Denmark, and the 5-year survival rate is only 8%. PDAC develops from precursor lesions with pancreatic intraepithelial neoplasia (panIN) being the most common, and cystic lesions as a second precursor. Unlike panINs, which are too small for detection with current imaging modalities, cystic lesions of the pancreas are increasingly diagnosed due to the extended use of cross-sectional imaging. Pancreatic cystic lesions may be observed in up to 13.5% of all MRI scans and 3% of all CT scans. There are several types of pancreatic cysts and each of them requires individual management, ranging from no treatment over watchful waiting to surgical resection according to their malignant potential.

Standard diagnostic workup includes cross-sectional imaging of the cystic lesions and, in selected cases endoscopic ultrasound (EUS) with aspiration of cyst fluid by fine needle aspiration (FNA), followed by cyst fluid cytology and tumor marker analysis. The diagnostic algorithm is based on International consensus guidelines established in 2006, and revised in 2012 and 2017, integrating clinical features with EUS-findings. The level of evidence in these guidelines is unfortunately low. A recent meta-analysis concluded that EUS and cyst fluid cytology have low sensitivity (54-63%), whereas the specificity is acceptable (88-92%) for detection of mucinous cysts. Low sensitivity is mainly due to absence of sufficient cellular material in the cyst fluid for definite diagnosis. Tumor marker analysis of cyst fluid, such as carcinoembryonic antigen (CEA), CA 72.4, CA 125, CA 19.9, and CA 15.3, have been studied extensively with CEA being the most accurate marker. A cut-off value of 192 ng/mL for CEA distinguishes mucinous from non-mucinous cysts with a good, albeit imperfect, accuracy of 80%. However, the value will not differentiate between IPMN and MCN, and more importantly, it does not correlate with the level of dysplasia or malignancy.

EUS-guided through-the-needle microbiopsy using the Moray™ forceps is a novel adjunctive. The device can be inserted through a EUS-FNA needle and used to obtain microbiopsies from different tissues in relationship to the gastrointestinal system. This instrument can be used in combination with EUS-FNA to subsequently obtain microbiopsies from the pancreatic cyst wall. Microbiopsies seem to represent a break-through in pre-operative classification of pancreatic cysts, as they provide histological material for examination of tissue architecture not readily accessible in FNA material. However, very little experience has been obtained hitherto. Even though this technique is currently described only in a few studies, it seems feasible and theoretically offers a higher quality of material than what can be obtained by EUS-FNA alone.

Utility of EUS-guided Microbiopsies in Pancreatic Cystic Lesions

Utility of EUS-guided Microbiopsies Combined With Auxiliary Molecular Techniques in the Workup of Pancreatic Cystic Lesions

All patients are evaluated at a multidisciplinary conference prior to microbiopsy procedure. A primary decision is made based on available imaging modalities and/or cyst fluid analysis (operation, follow-up or discontinuation from follow-up). Subsequently, each patient is once again evaluated at a multidisciplinary conference, and a possible change in management is noted. Clinical impact is defined as a proportion of the patients where a change in clinical management is observed.

Technical success is defined as a proportion of patients where a pancreatic cystic lesion is successfully punctured by a 19G FNA needle, and where at least one microbiopsy is obtained with the microbiopsy forceps.

Adverse events are defined in concordance with ASGE guidelines (Cotton PB, Eisen GM, Aabakken L et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454). All patients are contacted by telephone on day 3 following the procedure. Adverse event rate is an overall proportion of the patients where an adverse event is observed.

Diagnostic yield is defined as a proportion of the patients included where a definite histopathological diagnosis could be made on microbiopsy material.

Sensitivity, specificity as well as positive and negative predictive values are calculated by comparing microbiopsy diagnosis with gold standard (resected specimens).

Sensitivity, specificity as well as positive and negative predictive values are calculated by correlating different mutations with final diagnosis in patients that undergo surgery. NGS analysis is performed using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, USA). The multigene panel explores selected regions of 50 cancer-associated genes, among others KRAS, GNAS, CDKN2A and SMAD4 genes.

Rigshospitalet, Denmark

Herlev Hospital

Principal Investigator

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Cystadenoma

Cystadenoma, Serous

Neoplasms, Cystic, Mucinous, and Serous

Pancreatic Intraductal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

The registry will be populated with a retrospective cohort of patients previously identified as having pancreatic cysts.

The prospectively enrolled patients in this study are the primary population of interest.

There are no study-specific interventions, as this is a prospective registry. However, patients will be asked to complete approximately 1-2 hours worth of surveys on things such as demographics, medical and surgical history, and pancreatic cyst-specific questionnaires.

Survey

Charysa Santos, BS

Kimberly S Kirkwood, MD

M.D.

Kimberly Kirkwood, MD

Paige M Bracci, PhD, MPH, MS

Pancreatic cysts are found incidentally on 15-50% of CT and MRIs for all indications and their prevalence is increasing. Many of these cysts may be precursors to pancreatic cancer, and thus pose a substantial risk, however, the vast majority are benign. Increased detection of pancreatic cysts provides an opportunity to diagnose pancreatic malignancy at an early, curable stage yet also increases the potential to over-treat clinically insignificant lesions. This presents a clinical challenge to prevent unnecessary resection of indolent disease, with associated risks of infections, bleeding, diabetes, and costly disability. Unfortunately, there is little information on the epidemiology and natural history of pancreatic cysts to help guide management.

This study develops a large, prospectively managed, electronic, patient-directed pancreatic cyst registry based at UCSF. The UCSF Pancreatic Cystic Lesions Registry (PANC Cyst) will facilitate work to improve clinical care and understanding of pancreatic cysts by prospective follow-up of patients with cystic lesions, especially the diagnostically challenging small cysts, to identify factors related to cyst formation and progression to malignancy. Longitudinal data capture that includes clinical outcomes will also enable us to more precisely define anatomic, radiographic and biomarker information that can be used to differentiate populations of patients for whom surgery is indicated, surveillance is warranted, or no further evaluation is necessary.

Patients in this study will have the option of donating blood for biobanking, approximately 10cc of plasma and 10cc of serum. Patients will also have the opportunity to donate a saliva sample at the time of study registration, or at a later date.

Further, samples that are routinely collected for diagnostic purposes may be collected and banked at the time of their clinically routine procedure. If a patient consents to the use of extra material for research purposes, the biological samples will be banked and the blood, and/or pancreatic juice/cystic fluid, tissues, and saliva will be used for identification and characterization of potential biomarkers from de-identified samples.

UCSF PANC Cyst Registry

Population-Based Analysis of Neoplastic Changes in Cystic Lesions of the Pancreas.

While not the primary outcome measure, the development of cancer from a pancreatic cyst is a critically important study endpoint, which the investigators do not expect to be frequent occurrence.

If a patient with a pancreatic cyst experiences no or minimal change in size, and no development of worrisome or high-risk stigmata (Tanaka 2017), this will be considered to be an indolent lesion. Most patients will fall under this category.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Utility of EUS-guided Microbiopsies in Pancreatic Cystic Lesions	NCT03578445	Pancreatic Cyst IPMN Mucinous Cyst Pancreatic Aden...	EUS-guided micr... Next Generation...	18 Years -	Herlev Hospital
UCSF PANC Cyst Registry	NCT04291651	Pancreatic Cyst Pancreatic Neop... Pancreatic Canc... Pancreatic Dise... Pancreatic Intr... Intraductal Pap... Pancreatic Duct... Mucinous Cyst	Survey	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for mucinous cyst