Pancreatic Cyst

Pancreatic mucinous cystic neoplasm (MCN) is a precursor to invasive pancreatic adenocarcinoma which occurs almost exclusively in females in their 5th-7th decade. Currently the only option for MCN treatment and prevention of invasive pancreatic ductal adenocarcinoma (PDA) is oncologic resection. The clinical features of pancreatic MCN support the influence of sex hormones in the pathogenesis of the disease. Anti-hormonal therapy may therefore constitute an effective approach to treatment. Preliminary analyses from preclinical studies suggest that tamoxifen inhibits the spread and normal life cycle in MCN epithelial cells and fibroblasts. Investigators hypothesize that in humans, treatment with tamoxifen will lead to cyst regression or stabilization and may spare or delay the need for resection. Up to 15 participants not undergoing immediate resection will be enrolled and take tamoxifen orally for up to 24 weeks. The study will assess the feasibility of tamoxifen as a treatment for pancreatic MCN.

Hepato-Pancreato-Biliary (HPB) cancers originating in the liver, bile ducts, pancreas, and gall bladder represent a rising global health challenge, with incidence doubling in the UK over the past decade. Cholangiocarcinoma (CCA) and pancreatic cancer are particularly aggressive, often detected late due to non-specific symptoms and difficulties in sampling or imaging. In the UK, CCA affects around 3,000 people annually, with only 13% surviving 3 years, while pancreatic cancer has a 5-year survival of 8.3%. Diagnosis is complicated by the anatomical narrowness of the bile duct and the similarity between malignant and benign strictures. Standard imaging often cannot distinguish between inflammation and cancer, while tissue sampling is challenging, paucicellular, and limited in sensitivity, necessitating repeated biopsies. Yet, accurate characterisation is critical as NICE now recommends targeted therapies (FGFR2, NTRK, MSI-H/dMMR, IDH1 mutations) that require molecular profiling. Both CCA and PDAC display high heterogeneity, further complicating treatment. Emerging approaches such as Raman spectroscopy can map malignant tissues by detecting vibrational energy shifts, but require further validation due to weak signals. For focal or cystic HPB lesions not well visualised by conventional imaging, novel modalities like ultra-thin endoscopes with scattering/absorption imaging are being developed for improved early diagnosis. Management of biliary obstruction frequently involves stenting to restore bile flow, essential for palliation and pre-treatment optimization. However, stent failure from tumour ingrowth, displacement, or erosion remains common, and evidence for best stent use is limited. Novel approaches, including drug-eluting coatings and nanoparticle-mediated wireless treatment delivery, are being investigated. To overcome diagnostic and therapeutic barriers, flexible snake-like robotic systems with navigation, sampling, spectroscopy, and treatment capabilities are being developed. These devices, alongside ultra-thin endoscopes and integrated Raman spectroscopy, aim to characterise strictures, generate 3D imaging in ex-vivo HPB tissue, and permit targeted ablation. Parallel work will explore molecular and fluid-based biomarkers (blood, bile, cyst fluid) to support minimally invasive diagnosis and monitoring. Through integration of engineering, molecular diagnostics, and device innovation, this transdisciplinary research programme (UKRI and MRC funded) seeks to transform early detection, accurate diagnosis, and novel treatment of HPB cancers, thereby improving outcomes in CCA, pancreatic malignancy, and other clinically similar biliary disorders. Aim: To provide a detailed understanding of the characteristics (including clinical and molecular) of liver and pancreatic biliary focal lesions (inflammatory and cancerous) and create a bioresource of liver, pancreas, gallbladder and biliary tract associated tissue and fluids (biopsies, brushings, resected tissues, bile and cyst fluid and blood samples) in order to develop innovative tools for accurate diagnosis and treatment. Study Configuration: Prospective Longitudinal Cohort study Setting: Secondary care centre, Nottingham University Hospitals NHS Trust. (NUH). Co-ordinated by the NIHR Nottingham Biomedical Research Centre Description of interventions: This is an observational study involving collecting tissue or body fluids (such as bile or pancreatic cyst fluid) during clinical care in addition to collection of blood samples (for DNA, serum and plasma) and data collection. Surplus tissue residual to the requirements for standard care will be stored and used. Additional tissue samples and body fluid samples collected for research at time of clinical investigations will not be increasing the risk of the clinical procedure. Blood samples will be collected from patients at the time of enrolment in the study. These may be collected before and/ or after diagnosis is secured. Duration of study: Overall duration: 60 months Outcome measures: - To report the proportion of patients where adequate tissue could be retrieved from HPB biopsy to come to definitive diagnosis using standard of care. * To report the proportion of patients where adequate tissue could be retrieved from biopsy to perform molecular characterisation of HPB samples, beyond standard cyto/histology, using advanced optical-spatial technologies currently under development. * To report the proportion of patients where definitive diagnosis of mucinous cystic neoplasm could be made in patients with pancreatic cyst using standard care * To report the proportion of patients where molecular characterisation beyond standard cyto/histology could be made in patients with pancreatic cyst using exploratory new technologies under development through ex-vivo experiments * To report the correlation between Raman Spectroscopy and standard cyto/histology for identification of cancer in HPB samples

The purpose of this study is to establish a registry of patients with pancreatic diseases. Patients included in the registry may include those with: pancreatic cancer, precancerous lesions of the pancreas, inflammatory lesions of the pancreas, cystic lesions of the pancreas, and patients at high-risk of pancreatic cancer such as those with a family history of pancreatic cancer or with a family history of a syndrome known to be associated with pancreatic cancer. Pancreatic cancer is the fourth leading cause of death from cancer in the United States. However, little is known about the development of pancreatic cancer and pancreatic diseases in individuals with the above conditions. Knowledge of how family history, environmental exposures, and inflammatory lesion of the pancreas contribute to the development of pancreatic cancer and pancreatic diseases is essential. You may qualify to take part in this research study because you have inflammation in the pancreas, a pancreatic cyst, pre-cancerous lesions of the pancreas, pancreatic cancer, a family history of pancreatic cancer, or a family history of a syndrome known to be associated with pancreatic cancer. We will also be collecting a blood sample from all participants for DNA isolation. Sometimes we are born with genes or DNA that give us an increased or decreased chance of developing an illness later in life. Genetic material will be isolated from your blood for further study. You may also choose to provide additional blood samples for serum and plasma extraction. Serum and plasma are components of the blood which can be used to measure indicators of disease in the blood, called biomarkers,for pancreatic diseases. Clinical data and biological specimens contained in this study may be used for a wide variety of future related studies to the cause, diagnosis, outcome and treatment of pancreatic cancer. Funds for conducting this research are provided by Mount Sinai.

To learn if Hyperpolarized C-Pyruvate Magnetic Resonance (HP-MR) Spectroscopic Imaging can help doctors detect low-risk (benign) and high-risk (malignant) cysts.

The Florida Pancreas Collaborative wants to partner with individuals who are known to have, or are suspected to have a pancreatic lesion, tumor, cyst, mass, cancer, or pancreatitis and are undergoing diagnosis and treatment at a participating institution. The goals of this project are to build a large database of information obtained from blood, tissue, medical images, surveys and information from routine care to develop noninvasive diagnostic approaches that could be used as decision-making tools to effectively personalize clinical care.

The purpose of this study is to develop a minimally invasive test to diagnose pancreatic cancer at early stages of disease and monitor response to treatment.

The purpose of this study is for researchers to find ways of detecting pancreatic ductal adenocarcinoma/PDAC early to avoid the invasive procedure of surgery. The study researchers think a combination of imaging and a series of blood tests may be an effective way to detect PDAC early. In this study, researchers will look at whether a combination of the following types of imaging with blood tests can detect PDAC in pancreatic cysts: * The ImmunoPET scan (immune-positron emission tomography scan) with the imaging agent 89Zr-DFO-HuMab-5B1 * The HP MRI scan (hyperpolarized pyruvate magnetic resonance imaging scan)

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.

The standard of care for a patient with resectable pancreatic is to perform pancreatic resection which, even in the modern era is associated with significant complications and impact on quality of life, often in the setting of poor survival even in the best scenario. Currently, there is a lack of data on patient quality of life after such procedures, how quality of life changes throughout the course of care, and whether patients who undergo these procedures are satisfied with their decision. This research is aimed to understand the impact of pancreatic surgery on patients' quality of life, how that impact changes over time, and patient satisfaction (or regret) with their decisions. This work will help improve the pre-operative conversation to help patients decide whether undergoing a pancreatic resection aligns with their post-operative goals of care.

The DIPLOMA-3 trial is an international, multicenter, patient-blinded randomized controlled trial comparing laparoscopic and robot-assisted left-sided pancreatectomy. Patients with an indication for elective left-sided pancreatecomy for benign or premalignant lesions in the body or tail of the pancreas and considered eligible will be randomized between laparoscopic and robot-assisted resection.

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.

Pancreatic cancer is the fifth leading cause of cancer mortality in Hong Kong and the seventh leading cause of cancer mortality worldwide. In 2020, approximately 496000 new cases of pancreatic cancers were diagnosed globally . Pancreatic cancer is a highly fatal cancer with a case-fatality rate of 94.0% globally. In Hong Kong, both the incidence and mortality of pancreatic cancer have increased over the past decade. Due to the deep-seated location of pancreas, it is difficult to diagnose pancreatic cancer at an early stage, which in turn leads to delays in cancer treatment and poorer survival. Despite advances in oncologic treatment, the 5-year survival rate of metastatic pancreatic cancer remains poor (\~2.9%). As such, there has been growing interest to improve pancreatic cancer prevention and survival by: 1. reduction of modifiable risk factors (eg, cigarette smoking, obesity, diabetes), 2. screening for early detection of high-risk pre-malignant lesions in selected high-risks patients with strong family history of pancreatic cancer and/or certain germline mutations of pancreatic cancer susceptibility genes (eg, BRCA1, BRAC2, DNA mismatch repair genes in Lynch Syndrome, etc) by magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS), and 3. surveillance of pre-malignant precursor lesions such as mucinous pancreatic cystic neoplasms (PCN) by imaging and/or EUS to identify high-risk neoplastic progression indicated for surgical resection.

The objective of the study is to determine if this artificial intelligence system is capable of detecting abnormalities in the pancreas that are identified by an endoscopist at endoscopic ultrasound procedures.

Bio-repository to collect bio-specimens from patients with 1) pancreatic cysts and 2) patients at high risk, defined by family history and/or genetic mutations, for pancreatic cancer.

Several pancreatic neoplastic cystic lesions, such as IPMN (intrapapilary mucinous neoplasia), cystic neuroendocrine tumors (NET) and mucinous neoplasms, present a carcinogenetic risk, though it is yet unknown if this risk is increased in patients with pancreatic steatosis (PS). The primary objective of the study is to determine de prevalence of pancreatic steatosis in pancreatic neoplastic cysts and if pancreatic steatosis is increased in those lesions that pose a carcinogenetic risk. The secondary objective is to evaluate the prevalence of pancreatic steatosis in pancreatic adenocarcinoma.

Under the hypotheses that a more accurate patients selection could limit the problem of overtreatment and that benign intraductal papillary mucinous neoplasms (IPMN) have a distinguishable Endocrine/Metabolic/Inflammatory (EMI) profile from those with high-grade disease/invasive carcinoma, this study has three specific aims. The first aim is to evaluate and confirm the accuracy of the updated versions of International and European guidelines for the management of IPMN and it will be addressed by retrospectively applying the criteria included in the two guidelines on 350 patients with resected IPMN in order to determine the most accurate criteria to identify High Grade Dysplasia(HGD)/Invasive Carcinoma (IC). The second aim is to identify pre-operative biological and/or radiological/endosonographic biomarker(s) able to distinguish low- versus high-risk IPMN for cancer progression in a prospective study by enrolling a cohort of 186 (of which 145 surgically-resected) patients. The third aim is to prospectively validate biological and/or radiological/endosonographic biomarker(s) (previously identified and optimized) on a new cohort of 50 patients with IPMN undergoing surgical resection.

This is a randomized trial to compare the standard echoendoscope with the newly developed EndoSound Visual System in the evaluation of lesions in the gastrointestinal tract.

This study aims to find out whether quantitative and qualitative analysis, including genetic mutation analysis, of samples obtained from patients with pancreatic cysts is associated with the risk of malignancy, and helpful in the differential diagnosis of mucinous and serous cysts. The study design is a single-arm prospective cohort observational study. Using blood, pancreatic cyst fluid, and pancreatic cyst tissue, genetic mutation analysis and measurement of various biomarkers are performed, and the relationship between these and malignancy or whether they are helpful in distinguishing mucinous and serous cysts is analyzed. The primary outcome is genetic variants of pancreatic cysts associated with malignancy. The secondary outcomes are factors including genetic variants that differentiate mucinous from serous cysts.

The goal of the IMPACT project is to set up a data sharing infrastructure between expert centers for pancreatic surgery that enables training, testing and validation of computer science tools to improve quality of care for patients with pancreatic cancer.