IPMN Research

Intraductal Papillary Mucinous Neoplasm (IPMN) of the pancreas is the precursor lesion from which pancreatic ductal adenocarcinoma (PDAC) arises in 10% of individuals. IPMNs may be associated with low-grade or high-grade dysplasia or an associated adenocarcinoma. Accurately determining low-risk from high-risk IPMN is crucial for early detection initiatives for PDAC, so treatment can be offered before invasive cancer in high-risk individuals but without causing harm to low-risk individuals. Currently, imaging forms the basis for stratification but this is costly, resource intense and is limited in accuracy. There is a need to develop biomarkers to improve the risk stratification of IPMN.

A systematic review was conducted according to PRISMA-DTA guidelines by screening EMBASE, MEDLINE, CENTRAL and bibliographic reference lists for comparative studies. Studies were excluded if they were based on non-human subjects, not specific to IPMN, or determined IPMN from PDAC rather than low-grade from high-grade dysplasia in IPMN. Data extracted included study design, cohort demographics, specimen type, biomarker type, methodology for biomarker discovery, positive predictive value, negative predictive value, sensitivity, specificity or AUC value and were evaluated against the STARD checklist. Study quality was evaluated using the QUADAS-2 tool.

Study Group:

• James Birch-Ford, Medical Student, University of Liverpool

• Billy Rowley, Medical Student, University of Liverpool

• Mr. Munir Tarazi, ST6 OG Surgery/Clinical Research Fellow, North West Deanery/Imperial College London

• Mr. Martyn Stott, ST6 HPB Surgery/Clinical Research Fellow, North West Deanery/University of Liverpool

A national multi-centre study of the variation in surveillance and management of intraductal papillary mucinous neoplasms (IPMN) of the pancreas in the United Kingdom

Aim

The aim of this study is to assess current national practice with regards to diagnosis, surveillance and management of IPMN of the pancreas in both district general hospitals and specialist regional pancreas centres, including network arrangements, in the United Kingdom.

Primary Outcome

To assess national practice against the European Study Group on Cystic Tumours of the Pancreas Pancreatic Cystic Neoplasm Guidelines (2018) and Fukuoka Guidelines (2017) for the management of IPMN of the pancreas.

Secondary Outcomes

1.     To assess national variability in diagnostic and surveillance pathways between secondary and tertiary services

2.     To assess regional variability in network arrangements for diagnosis and surveillance of IPMN

3.     To assess regional variability in MDT decision making with regards to the surgical management of IPMN

Part 1: Site Feasibility Study

Study Group:

• Scott Oakes, ACP, Dept of Gastroenterology, Wythenshawe Hospital, Manchester University NHS FT

• Lauren Hill, ACP, Dept of Gastroenterology, Wythenshawe Hospital, Manchester University NHS FT

• Dr. Sajjad Mahmood, Consultant PB Physician, Dept of Gastroenterology, Wythenshawe Hospital, Manchester University NHS FT

• Mr. Martyn Stott, ST6 HPB Surgery/Clinical Research Fellow, North West Deanery/University of Liverpool

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and bound to become the second most frequent cause of cancer-related death in the Western world. There are two types of PDAC precursor lesions, namely pancreatic intraepithelial neoplasias (PanIN) and mucinous cysts. The latter are subdivided further into intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). In particular IPMNs have a high potential to develop into malignant tumors with a bad prognosis and are therefore of high clinical relevance. They are frequently discovered through incidental cross-sectional imaging. Diagnostically, three IPMN grades are described: low-grade and high-grade dysplasia (also called carcinoma in situ) as well as IPMN with an associated carcinoma. On the basis of clinical evidence, low-grade IPMN dysplasia are considered benign with a low risk of malignant progression. They have a 5-year disease-specific survival rate of 97%, as compared with 84% and 39% of patients with high-grade and invasive IPMN. They are kept under close surveillance to monitor further development of the disease. High-grade dysplasia is a premalignant form and IPMNs with an associated carcinoma have already become malignant. Distinguishing high-risk from low-risk IPMN patients accurately is critical to give patients the appropriate treatment. If the intervention is late, a highly malignant tumor could develop which results in poor prognosis. If surgery is performed when not required, it poses an unnecessary risk to the patient's health.

Current indicators of “high risk lesions” include positive cytology for malignant, high-grade dysplasia, tumor-related jaundice, enhancing mural nodes, main pancreatic duct dilatation, tumor growth-rate, cyst diameter, increased carbohydrate antigen 19–9 (CA19–9) blood concentration, new-onset of diabetes mellitus, and diagnosis of pancreatitis. Despite this large number of diagnostic features, however, diagnosis is not sufficiently accurate. Also imaging does not solve the problem; resected IPMN samples frequently reveal other grades of malignancy than predicted prior to resection. IPMN screening is also costly to health services and is a resource burden.

Aims

IPMN-Detect and Discover is a translational observational cohort study with the aim of providing bioresources throughout Europe to allow multi-omic (genomic, transcriptomic, proteomic and metabolomic (Volatile organic compound)) biomarker discovery linked to radiomics and pathological outcomes for individuals undergoing IPMN surveillance. The aim is to develop a biomarker to determine individuals who would require further intensive imaging follow up for high risk IPMN and to offer them surgery prior to invasive carcinoma development.

Methods

Individuals enrolled in the study would undergo standard IPMN screening according to international guidelines. At each imaging visit, blood and breath samples would be taken for biomarker discovery as well as symptom and anthropological measurements. Images will be stored for radiomic analysis. If endoscopy is undertaken, they will give cyst fluid samples for storage. If surgery is undertaken, blood and breath samples will be taken on the day of surgery. Samples of the tumour will be taken and snap frozen. Histological outcomes will be available.

Outcomes

The primary outcome is to determine if a non-invasive biomarker can be established which allows high and low risk IPMN lesions to be segregated. The secondary outcome is to provide a well characterized cohort of individuals undergoing IPMN surveillance with associated biosamples to allow for the future discovery and validation of biomarkers in this area.