Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Cysts

Pancreatic Cyst

Pancreatic Diseases

Gastrointestinal Diseases

Pancreatic Cancer

Megan Fry

Diana Burke

Veronica Oria

Rahul Pannala

Samer El-Dika

Chloe Bennett

Thiruvengadam Muniraj, MD, MRCP

Kylie Ning

Anne Marie Lennon

Roya Dastjerdi, MPH

Mandeep Sawhney, MD

Maria Marotta-Kollarus

Jessica Widmer, MD

Tomas Gonda, MD

Sharon Slomovich

Frank Gress, MD

Chandra Kovvali

Mohamed Othman, MD

Somashekar Krishna, MD, MPH

The study schema is shown in Figure 4. (A) All patients referred to one of the participating academic centers for EUS evaluation of the PCL will be enrolled in the protocol if they satisfy inclusion criteria. Patient consent will be obtained during the clinic visit or prior to their EUS. EUS-guided nCLE imaging is first performed (B) followed by EUS-guided FNA and aspiration of cyst fluid. The cyst fluid is analyzed for CEA and cytology. As per institutional standard of care, the cyst fluid is also sent for molecular analysis. The results of the cyst fluid molecular analysis (B) will be utilized for the most likely diagnosis. Based on institutional multidisciplinary tumor board meetings, surgery is performed as indicated (C). Surgical histopathology serves as "gold standard" for diagnosis. It is anticipated that the majority of patients will undergo surgical resection after their EUS.

Confocal Laser Endomicroscopy as an Imaging Biomarker for the Diagnosis of Pancreatic Cystic Lesions

Confocal Laser Endomicroscopy as an IMaging Biomarker for the Diagnosis of Pancreatic Cystic Lesions

Diagnostic accuracy of confocal laser endomicroscopy and/or cyst fluid molecular markers and/or composite clinical and imaging features for the diagnosis of mucinous PCLs, PCLs with malignant potential, specific PCL types, and mucinous PCLs with advanced neoplasia.

Diagnostic accuracy of confocal laser endomicroscopy and/or composite clinical and imaging features for the risk stratification of IPMNs

Optimal quality of imaging obtained during in vivo confocal laser endomicroscopy of pancreatic cystic lesions

American College of Gastroenterology

The National Pancreas Foundation

Ohio State University

Professor

Cystadenoma

Cystadenoma, Mucinous

Cystadenoma, Serous

Pathological Conditions, Anatomical

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Cystic, Mucinous, and Serous

Pharmaceutical Solutions

All Drugs and Chemicals

Gastrointestinal Agents

Pancrelipase

Pancreatin

For inoperable patients with indeterminate cystic lesions of the pancreas,a EUS FNA will be performed and molecular biology analysis of pancreatic intra-cyst fluid collected by EUS FNA will be performed.

For operable patients, after the pancreatic surgery, molecular biology analysis of extemporaneous pancreatic tissue specimen biopsy will be conducted.

The EUS FNA will be performed according to the Francophone Club of Echo Endoscopy recommendations.

For molecular biology technique, the samples will be processed within the UMR_S910 unit. Nucleic acids will be extracted from the intra-cystic fluid or, for post-operative patients, from a resected specimen that will be collected into a tube containing a nucleic acid stabilization solution (Allprotect Tissue reagent, Qiagen).

The nucleic acids will be extracted and then sequenced. The sequencing technology chosen (HaloPlexHS, Agilent) allows a detection close to 1% in allelic frequency. This new technical approach that links high sensitivity and specificity is also suitable with degraded and/or low-volume ( \<50ng) DNA.

Molecular biology analysis of pancreatic intra-cyst fluid

Arthur Laquière, MD

The main objective of the study is to compare the diagnostic accuracy of intra-cystic fluid DNA molecular analysis to standard diagnostics.

The secondary objective of the study is to evaluate the feasibility of intra-cystic fluid DNA molecular analysis.

Multicenter study to determinate the feasibility of intra-cystic fluid DNA molecular analysis in patients with suspected cystic tumours of pancreas in whom EUS FNA is clinically indicated.

Morphological criteria obtained by MRI and computerised tomography (tumor characterization (size, metastases presence, dilatation of bile ducts), etiologic diagnosis, serious symptoms), biological exams (biomarkers), cytological analysis will lead to a diagnosis and a treatment.

The goal of this study is to compare this standard diagnostic modalities to diagnosis obtained by intra-cystic fluid DNA molecular analysis.

Is the DNA molecular analysis improve the diagnosis accuracy.

First 20 patients for pilot study to test the feasibility of the molecular analysis then 120 patients to continue the trial.

Feasibility of Molecular Biology in Pancreatic Cyst Tumors

Study of Feasibility and Diagnostic Profitability of Intra-cyst Fluid Molecular Biology Analysis in Pancreatic Cyst Tumors.

The nucleic acids of the samples will be extracted and then sequenced on a panel of about 70 genes implicated in the pancreatic tumorigenesis and targeting RAS, MAPK, AKT, JAK-STAT, WNT, TGFB, TP53 and Repair BRCA, ATM. The selected sequencing technology (HaloPlexHS ®, Agilent) will be used. A comparison of the molecular profiles between the cystic fluid and the surgical specimen will be carried out and then confronted with the pathology, biological, radiological and clinical characterization

The nucleic acids of the samples will be extracted from the different cyst fluids and then sequenced. A comparison of the molecular profiles between the different cystic fluids will be carried out and then confronted with the pathology, biological, radiological and clinical characterization

Ramsay Générale de Santé

Hospital St. Joseph, Marseille, France

Principal Investigator Dr Arthur LAQUIERE

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Individuals without history of PDAC meeting any of the following criteria:

A. 2+ relatives with PDAC on same side of family; 2 are first degree related to each other and at least 1 is first degree related to subject; age ≥ 50 years or ≤10 years younger than earliest PDAC in family at diagnosis.

B. 2+ first degree relatives with PDAC; age ≥ 50 years or ≤ 10 years younger than earliest PDAC in family at diagnosis.

C. BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, MSH6, PMS2, EPCAM pathogenic or likely pathogenic variant AND 1 first or second degree relative with PDAC; age ≥ 50 years or ≤ 10 years younger than earliest PDAC in family at diagnosis.

D. Familial Atypical Moles and Malignant Melanoma (FAMMM) with pathogenic or likely pathogenic CDKN2A variant; age ≥ 40 years.

E. Peutz-Jegher syndrome with STK11 pathogenic or likely pathogenic variant; age ≥35 years.

F. Hereditary pancreatitis with PRSS1 pathogenic or likely pathogenic variant and history of pancreatitis; age ≥ 40 years.

Individuals without history of PDAC meeting any of the following criteria:

A. ATM, BRCA1, BRCA2, or PALB2 pathogenic or likely pathogenic variant regardless of family history; age ≥50 years.

B. Two or more (2+) relatives with PDAC on the same side of family, any degree of relation, not meeting other criteria above; age ≥50 years or ≤10 years younger than earliest PDAC in family at time of diagnosis.

C. One (1) first degree relative with PDAC at age ≤45 years; ≤10 years younger than PDAC diagnosis in family member at time of diagnosis.

A. Individuals meeting criteria for Cohorts 1 or 2 EXCEPT age (i.e. too young to qualify for Cohorts 1 or 2); age ≥ 18 years.

A. Individuals without history of PDAC presenting for evaluation who do not meet any criteria for the other cohorts after collection of full family history and/or germline testing, eg. they have only 1 relative with PDAC; age ≥ 18 years.

Individuals with a personal history of PDAC meeting any of the following criteria (age ≥ 18 years for all subgroups):

A. Family history includes at least one first degree relative with PDAC, or 2 relatives with PDAC who are first degree related to each other.

B. Personal or family history of a pathogenic or likely pathogenic germline variant in ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11.

C. Diagnosed with PDAC at ≤ age 45.

Individuals with pancreatic cysts (age ≥ 18 years for all subgroups):

A. Individuals with a pancreatic cystic neoplasm (IPMN) and/or mucinous cystic neoplasm (MCN) and/or PanIN not meeting any criteria for Cohorts 1-3 or 6 (no personal history of PDAC, no known family history of PDAC, no known pathogenic germline variants linked to PDAC risk present in cohorts 1C, 2A, 1D, 1E, and 1F).

B. Individuals with a pancreatic cystic neoplasm (IPMN) and/or MCN and/or PanIN without PDAC and with at least one of the pathogenic or likely pathogenic gene mutations present in cohorts 1C, 2A, 1D, 1E, and 1F and/or a first degree relative with PDAC.

Individuals with a personal history of pancreatitis meeting any of the following criteria (age ≥ 18 years for all subgroups):

A. Chronic pancreatitis. B. At least 2 episodes of acute pancreatitis.

Individuals with one of the following conditions and treatment naïve (age ≥ 18 years for all subgroups):

A. Biopsy-proven, clinical stage I-II PDAC and candidate for surgical resection.

B. Clinical findings suspicious for early stage PDAC prior to biopsy.

Harmeet Dhani, MD, M.Sc

Rebekah White, MD

Harmeet Dhani, MD

Hoon David, PhD

Thomas Lomis, MD

Priyanka Kanth, MD

Steven Hughes, MD

Bhanu Visvalingam, MD

Sapna Syngal, MD

ExoLuminate is a nationally-enrolling registry study designed for earlier detection of cancer in patients at elevated risk or clinically-suspicious for pancreatic ductal adenocarcinoma (PDAC).

Those with elevated risk for PDAC can include individuals with intraductal papillary mucinous neoplasms, family history of pancreatic cancer, germline mutations in genes known to be associated with cancer, and a personal or family history of pancreatitis.

The goal of the study is to compare the performance of ExoVerita™ assay in early detection of PDAC to current standard-of-care methods of surveillance.

Biological Dynamics, Inc. has developed a non-invasive blood test ("liquid biopsy") that can identify early-stage disease with high sensitivity and specificity. The proprietary ExoVerita™ assay uses alternating current electric (ACE) field to isolate extracellular vesicles (EVs) for differentiated multiomics applications and includes an optimized machine learning algorithm to identify a panel of EV-bound protein biomarkers in patient's plasma in order to detect PDAC at earlier stages.

ExoLuminate is a prospective, multi-center, observational registry study designed to evaluate the non-inferiority of the performance of the ExoVerita™ assay in detecting pancreatic ductal adenocarcinoma (PDAC) in high-risk or clinically-suspicious populations in comparison to standard-of-care methods.

The study is planned to recruit a minimum of 1000 U.S. adults over 3-years (with a 2-year follow-up for data collection).

Eligible subjects will be evaluated using the ExoVerita™ assay through blood donation(s) at specified time intervals. Overall, this study poses minimal risk to subject.

ExoLuminate Study for Early Detection of Pancreatic Cancer

Exoluminate Study: Observational Registry Study to Assess Exo-PDAC Assay Performance for Detection of Pancreatic Adenocarcinoma (PDAC) in High-Risk or Clinically Suspicious Patients

Evaluation of stage distribution (SEER) at diagnosis

Medical College of Wisconsin

Dana-Farber Cancer Institute

Biological Dynamics

Medical Director

All subjects will undergo the intraoperative pancreatoscopy with SpyGlass procedure.

Visualization of main pancreatic duct with SpyGlass catheter.

SpyGlass

Marco Del Chiaro, MD

G.V. Rao, MD

Richard Burkhart, MD

Marc Besselink, MD

Yi Miao, MD

Sohei Satoi, MD

Urban Arnelo, MD

Christian Schmidt, MD

To demonstrate the added value of intraoperative pancreatoscopy in patients undergoing partial pancreatic resection for the treatment of Intraductal Papillary Mucinous Neoplasm (IPMN) as it pertains to detection of discontinuous (skip) lesions in the remnant pancreas; to generate a hypothesis for a subsequent randomized control trial.

The primary objective of this study is to demonstrate the added value of intraoperative pancreatoscopy in patients undergoing partial pancreatic resection for the treatment of Intraductal Papillary Mucinous Neoplasm (IPMN) as it pertains to detection of discontinuous (skip) lesions in the remnant pancreas. A secondary study objective is to generate a hypothesis for a subsequent randomized controlled trial comparing diagnostic accuracy of intra-operative pancreatoscopy and SpyBite™ with the diagnostic accuracy of intra-operative frozen section in patients undergoing resection

Intra-operative Pancreatoscopy in Patients With IPMN

Intra-operative Pancreatoscopy in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN)

Rate of detection of discontinuous (skip) lesions along the main pancreatic duct of patients with IPMN using intraoperative pancreatoscopy based on visual impression of IPMN and/or pancreatoscopy guided biopsies

Ability to advance the pancreatoscope along the entire main pancreatic duct length or until clinically needed; to visualize the potential lesion(s); or to obtain a tissue sample with SpyBite where applicable

Evaluate all serious adverse events related to the intraoperative pancreatoscopy procedure and/or device

Recurrence of IPMN within 5 years post-surgery evaluated with regular MRI or alternative radiological method

Comparison based on exploration with Spy Glass of the resected specimen

Based on intra-operative impression and on review of recorded pancreatoscopy images/videos

Boston Scientific Corporation

Precancerous Conditions

patients referred to Johns Hopkins Hospital for evaluation and or treatment for 1 or more pancreatic cysts

Anne Marie O'Broin-Lennon, MD

The aim is to propose and prospectively validate a diagnostic approach and model for prediction of mucinous versus non-mucinous, and malignant versus non-malignant pancreatic cysts using a combination of clinical, radiologic, and biomarker characteristics.

This combined cross-sectional and prospective single center clinical and translational study involves a collaborative multidisciplinary team composed of gastroenterologists, surgeons, radiologists, and basic scientists. Eligible patients with solitary or multiple pancreatic cysts referred for diagnostic evaluation and/or surgical treatment will undergo initial radiographic imaging with high-resolution CT, MRI/MRCP, and EUS/FNA as part of standard medical care at Johns Hopkins Hospital. This is a three-phase study.

In Phase I, eligible patients with pancreatic cysts will undergo initial radiographic imaging (high-resolution CT, MRI/MRCP, endoscopic ultrasonography (EUS) with fine needle aspiration (FNA)) as part of standard care at the Johns Hopkins Hospital. Patients will be categorized according to the presence of symptoms referable to the cyst or imaging features concerning for malignancy based on the initial radiographic assessment. Symptomatic patients, or those with concerning features, will be referred for surgical resection. The pathologic features and final diagnosis of resected pancreatic cysts will be compared with preoperative clinical, radiologic, and cyst fluid test results.

Asymptomatic patients with low-risk features at baseline radiographic and endoscopic imaging will enter Phase II. Patients will be followed on a prospective periodic surveillance schedule according the consensus clinical guidelines with either CT or MRI to monitor for new or metachronous cystic neoplasms. Those who develop symptoms or concerning features will have a repeat EUS/FNA as well as imaging with the opposite axial imaging modality, and will be referred for surgery if a suspicious lesion is detected.

Patients who have surgery either during Phase I or Phase II, will enter post-surgical surveillance (Phase III). Patients will be followed using a prospective periodic surveillance schedule according the consensus clinical guidelines with either CT or MRI to monitor for new or metachronous cystic neoplasms. Those who undergo surgery after surveillance in Phase II will continue with the imaging modality they were originally evaluated with prior to surgery.. Patients who develop symptoms or high-risk features on imaging will have a repeat EUS/FNA as well as imaging with the opposite axial imaging modality and will be referred for surgery if a suspicious lesion is detected. Samples will be collected prospectively for biomarker analysis. Cyst fluid, pancreatic juice and blood will be collected during EUS and blood will be collected yearly during the outpatient clinic visit. Patients will be followed for three years.

The Clinical,Radiologic,Pathologic and Molecular Marker Characteristics of Pancreatic Cysts Study

The Clinical,Radiologic, Pathologic and Molecular Marker Characteristics of Premalignant and Malignant Pancreatic Cysts Study

1)to determine the prevalence and incidence of malignancy in pancreatic cysts according to cyst size and concerning features

To collect tissue samples (cyst fluid and blood) for research on molecular markers in pancreatic cysts

To develop a panel of candidate biomarkers in pancreatic juice and serum as indicators of prevalent and incident malignancy in patients with surgically-proven neoplastic pancreatic cysts compared to non-neoplastic cysts (pseudocysts, lymphoepithelial cysts, congenital cysts)

to determine the sensitivity, specificity, and overall accuracy of pancreatic protocol CT, EUS, and/or MRCP in patients with pancreatic cysts, using surgical pathology as the reference standard

to calculate difference in diagnostic accuracy and clinical impact (change in preoperative diagnosis and treatment plan) of additional diagnostic tests (EUS and/or MRCP) over pancreatic protocol CT for the diagnosis of neoplastic/malignant pancreatic cysts.

to determine the factors associated with prevalent and incident malignancy in pancreatic cyst using a multivariate model including clinical, radiologic, and molecular markers

to determine the best model for prediction of malignancy in pancreatic cysts using multiple logistic regression and discriminant function analysis, including clinical, radiologic, and molecular markers

Lustgarten Foundation

Johns Hopkins University

Mucocele

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

Pancreatic cancer patients evaluated at the Pancreatic Surgery Unit of the Pancreas Institute of the University of Verona will be enrolled. Fifteen PC patients per stage will be selected (15 Stage I/II, Stage III, Stage IV). Patients may have been scheduled for surgery or for biopsy for future systemic treatments. An oral microbiota (dental plaque) sample will be collected and a periodontal and dental assessment will be performed, before any therapeutic procedure, together with orthopantomography

Age-matched (+- 5 years) healthy controls referring to the Odontostomatology Unit for oral procedure according to clinical practice, with a recent (not longer than 12 months) cross-sectional abdominal imaging excluding gastrointestinal cancers.

Pancreatic cancer patients evaluated at the Pancreatic Surgery Unit of the Pancreas Institute of the University of Verona will be enrolled. Fifteen PC patients per stage will be selected (15 Stage I/II, Stage III, Stage IV). Patients may have been scheduled for surgery or for biopsy for future systemic treatments.

Patients suffering from IPMNs evaluated at outpatients clinics or scheduled for surgery.

Dental plaque sampling

qPCR

Salvatore Paiella, MD, PhD

Erica Secchettin, PharmD

Salvatore Paiella

Erica Secchettin

Francesca Zotti

Pancreatic cancer (PC) is a solid malignancy with a dismal prognosis. It has a 5-year survival rate of approximately 8%. This is due to the usually late diagnosis, to chemoresistance, and to intrinsic biological aggressiveness. Risk factors for PC are smoking, alcohol, chronic pancreatitis, obesity, and diabetes. Recently, research has been dedicated to the identification of a causal connection between certain pathogenic microorganisms, especially of the oral flora, and PC. This would ultimately allow to identify new biomarkers to adopt for early diagnosis, or to create new strategies for prevention.

Oral microbiota, periodontal disease and neoplastic risk

When referring to "oral microbiota" (OM), about 700 hundreds bacterial species are mentioned, colonizing the oral cavity. A change in the normal flora of the oral cavity is commonly indicated with the term "dysbiosis".

The causal connection between oral microbiota, periodontal disease and neoplastic risk is possibly triple. First, it has been found that oral flora substantially differentiates between cancer patients and controls. In particular, the most predominant phyla in cancer patients are Firmicutes and Actinobacteria, whereas Proteobacteria, Fusobacteria, and Bacteroides are more common in healthy controls. This highlights the possibility of a direct causal connection between dysbiosis and neoplastic risk. Second, oral dysbiosis represents the main risk factor of PD that per sé is a risk factor of many cancers. Third, the conditions leading to oral dysbiosis (alcohol, smoking, obesity, diabetes, chronic drugs intake, dietary habits, etc.) are the most well known risk factors either for cancer and oral dysbiosis. The common denominator is always represented by chronic inflammation and migration of microorganisms to distant sites, ultimately promoting neoplastic progression.

This tangled net of causal connections sheds light on the potential important role of the oral cavity and PD as independent risk factors for many cancers, and as modifiable elements to reduce the neoplastic risk and to perform prevention(15).

Oral microbiota, periodontal disease and pancreatic cancer

In 2012, the pioneering study by Farrell et al. showed that bacteria of the OM can discriminate PC patients from healthy subjects. Since then, few other studies have shown that changes of the OM are independent risk factors for PC and that the OM of PC patients differs than controls. The involved bacterial species are many and their role seems to be contrasting on the basis of the study considered. Farrell et al. found that the combined adoption of Neisseria elongata and Streptococcus mitis distinguished PC patients from healthy controls (both showed low levels in PC patients, AUC of combined sensitivity 0.9), and that higher levels of Granulicatella adiacens and Streptococcus Mitis distinguished PC patients from chronic pancreatitis ones. Torres et al. found a higher ratio of Leptotrichia to Porphyromonas in PC patients. Fan et al. reported that Porphyromonas gingivalis, Prevotella intermedia, Alloprevotella and Aggregatibacter actinomycetemcomitans are associated with a higher risk of PC, whereas Fusobacteria and Leptotrichia were associated with a decreased risk. Another study evaluating the diversity of OM in three groups of individuals (PC patients, patients suffering from Intraductal papillary mucinous neoplasms \[a pancreatic preneoplastic condition\], and healthy controls), excluding current smokers and users of antibiotics, found no differences in the OM, although patients with PC had a higher proportion of Firmicutes compared with Intraductal Papillary Mucinous Neoplasms (IPMNs) and controls. Lastly, a recent study by Gaiser et al. showed that the cystic fluid of patients submitted to surgery for IPMNs contained bacterial species that are commonly found in the oral cavity, including, among the others, Granulicatella adiacens, Fusobacterium nucleatum. These two, in particular, were higher in the cohort of individuals with IPMNs with high-grade dysplasia, indicating a pivotal role in tumorigenesis(19).

As regards PD, the first studies demonstrating an association between PD and PC date back to the mid of 2000's, and they were confirmed afterward, even adjusting confounders such as diabetes, pancreatitis, hyperlipemia, smoking or alcohol-related conditions. PD is strictly connected to oral hygiene, that seems to be associated to an increased risk of PC. It is now clear that PD can concur to development of PC in several ways, promoting chronic inflammation, spreading continuously to distant organs (including pancreas) pro-tumorigenic bacteria, or promoting a chronic alteration of the immune function that make the individual more prone to develop a cancer.

Pancreatic Cancer and Oral Microbiome

Pancreatic canceR pErioDontAl sTatus and Oral micRobiome - PREDATOR Study

According to the periodontal status (appropriate scores will be used), patients will be divided into distinct groups. The proportional means of abundance of selected genera and species, and bacterial load (real-time data) between these groups will be analyzed using the Mann-Whitney U-test. Correlations between mean distributions of the genera and species and the parodontal status scores values will be analysed using the Spearman Correlation Coefficient.

Azienda Ospedaliera Universitaria Integrata Verona

Disease Progression

Pancreatic Intraductal Neoplasms

Hypoglycemic Agents

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Analgesics

Metformin

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus sulindac. The sulindac starting dose is 200 mg by mouth 2x daily. Patients will continue drug for 3 years during follow-up.

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus placebo. Patients will continue placebo for 3 years during follow-up.

Patients will be randomized to receive standard radiographic/endoscopic surveillance plus sulindac. The sulindac starting dose is 200 mg by mouth 2x daily. Randomization will be performed at Duke and stratified by (1) the presence of high-grade dysplasia on the operative pathologic report and (2) the use of metformin at the time of enrollment. Patients will be provided the study drugs by a Duke, MSK, MGH, or JHH pharmacist. Patients will continue drug/placebo for 3 years during follow-up.

Sulindac 400 MG

Placebo

Peter Allen, MD

This is a multi-center randomized double-blind placebo controlled trial of patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The primary objective is to evaluate the effect of sulindac on the presence or absence of progression of IPMN after up to 3 years of treatment.

Patients without contraindications will be considered to be eligible and will be required to have a cross-sectional imaging study of the pancreas by CT scan or MRI within 3 months of study entry to document residual IPMNs and to rule out any evidence of pancreatic cancer. Patients will be randomized to receive either sulindac (200 mg p.o. BID) plus standard radiographic and endoscopic surveillance or placebo plus standard radiographic and endoscopic surveillance. Randomization will be stratified by (1) whether the patient had high-grade dysplasia identified in the initial resection specimen (resected patients only) and (2) whether the patient is taking metformin at the time of randomization.

This is a phase 2 multicenter, randomized, double-blind, placebo-controlled clinical trial of patients who have high-risk intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Patients will be randomized in a 1:1 fashion and stratified by whether the patient had high-grade dysplasia (yes vs. no vs. no resection) identified in the initial resection specimen (for resected subjects), and whether or not the patient is taking metformin at the time of randomization. Patients will be required to have undergone an MRI or CT angiogram for IPMN active surveillance in accordance with the standard practice at the enrolling institution within 3 months of study entry. The CT imaging study will be used to document baseline IPMN characteristics and to ensure that there is no evidence of a preexisting pancreatic cancer.

Following randomization, patients will take the study drug or placebo twice daily for up to 3 years. Both the study drug arm and the placebo arm will undergo standard laboratory, radiographic, and endoscopic assessment for IPMN progression. Every 6 months, patients will undergo assessment of serum CMP, CBC, and CA19-9. EUS will be performed 6 months after randomization (+/- 4 weeks) and then annually. CT or MRI will be performed 1 year after randomization (+/- 4 weeks) and then annually. The intent of these timings is to have the EUS and CT/MRI be on an alternating 6-month schedule per standard of care.

Patients, nurses, and physicians will be blinded to the randomization. Study drug will be provided to patients in the outpatient clinic or mailed to their home. Pill diaries will be provided at the time that the study drugs are given and will be evaluated every 6 months, at the time of routine follow-up.

Safety and efficacy will be assessed throughout the treatment period. Assessment for study drug complications will be made by phone call every other month (in between routine follow-up) and at routine follow-up every 6 months by the attending surgeon or designee, until the end of the study. If a complication is identified, the study drug will be discontinued. Patient evaluations will be scheduled bi-annually for the primary endpoint and off-schedule evaluations may be made to address symptoms or clinical concerns as they arise.

The investigators plan to accrue 100 patients and will follow all patients for up to 3 additional years until protocol defined progression or study closure, whichever occurs first.

The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)

Preventing an Incurable Disease: The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)

Data will only be shared through publication.

2. Cyst fluid obtained at the time of annual EUS or surgical resection will be used to determine whether cyst fluid inflammatory marker analysis can identify progression. Antibody bead array analysis will be used to assess whether previously developed biomarker models for high-risk IPMN (IL-4/sFASL and MMP-9/CA72-4) can identify patients with an increased risk of radiographic progression. Archival tissue will be collected to validate cyst fluid analysis.

Patients will be determined to have progressed if they have:

1. New cystic lesion(s) of the pancreas \>1 cm in diameter (or initial lesion(s) \<5 mm that are now \>1cm),
2. Doubling of the diameter of any preexisting cyst initially measuring ≥5 mm
3. Increase in diameter of the main pancreatic duct by \>3mm
4. Pancreatic resection
5. The development of pancreatic adenocarcinoma

1. All initial and follow-up radiographic imaging will be quantitatively assessed for radiographic changes associated with progression. Utilizing a recently described radiomics approach to the evaluation of imaging in patients with IPMN, the investigators will further explore the set of 256 imaging features that broadly describe variation in radiographic enhancement patterns (i.e. heterogeneity). Using image analysis techniques, the investigators will derive quantitative measurements of the cyst wall and will determine the presence and degree of solid enhancing component suggestive of malignancy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Confocal Laser Endomicroscopy as an Imaging Biomarker for the Diagnosis of Pancreatic Cystic Lesions	NCT03492151	Pancreatic Cyst		18 Years -	Ohio State University
Feasibility of Molecular Biology in Pancreatic Cyst Tumors	NCT03305146	Pancreatic Cyst Pancreas Cyst Serous Cystaden... Mucinous Cystad... IPMN	Molecular biolo...	18 Years -	Hospital St. Joseph, Marseille, France
ExoLuminate Study for Early Detection of Pancreatic Cancer	NCT05625529	Pancreas Cancer Exosomes Extracellular V... Pancreatic Neop...		18 Years -	Biological Dynamics
Intra-operative Pancreatoscopy in Patients With IPMN	NCT03729453	Intraductal Pap...	SpyGlass	18 Years -	Boston Scientific Corporation
The Clinical,Radiologic,Pathologic and Molecular Marker Characteristics of Pancreatic Cysts Study	NCT01202136	Pancreatic Cyst... Pancreatic Canc...		18 Years -	Johns Hopkins University
The Clinical,Radiologic,Pathologic and Molecular Marker Characteristics of Pancreatic Cysts Study	NCT01202136	Pancreatic Cyst... Pancreatic Canc...		18 Years -	Johns Hopkins University
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
ExoLuminate Study for Early Detection of Pancreatic Cancer	NCT05625529	Pancreas Cancer Exosomes Extracellular V... Pancreatic Neop...		18 Years -	Biological Dynamics
Pancreatic Cancer and Oral Microbiome	NCT04993846	Oral Microbiome Pancreatic Canc... IPMN Parodontopathy	Dental plaque s... qPCR	18 Years - 75 Years	Azienda Ospedaliera Universitaria Integrata Verona
The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)	NCT04207944	IPMN IPMN, Pancreati...	Sulindac 400 MG Placebo	21 Years - 85 Years	Duke University
A Long-term Follow-up Cohort Study in Patients With Intraductal Papillary Mucinous Neoplasm	NCT05593393	IPMN, Pancreati...	Endoscopic ultr...	18 Years -	Peking Union Medical College Hospital
The Prevention of Progression to Pancreatic Cancer Trial (The 3P-C Trial)	NCT04207944	IPMN IPMN, Pancreati...	Sulindac 400 MG Placebo	21 Years - 85 Years	Duke University
Intraductal Papillary Mucinous Neoplasm With Malignant Change	NCT02044926	IPMN		20 Years -	Asan Medical Center
Intraductal Papillary Mucinous Neoplasm (IPMN) Database - A Tool to Predict Pancreatic Cancer	NCT05117723	IPMN, Pancreati... IPMN		18 Years - 90 Years	St Vincent's Hospital Melbourne

Spots Global Cancer Trial Database for ipmn

Every month we try and update this database with for ipmn cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ipmn

Every month we try and update this database with for ipmn cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ipmn cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.