Hôpital Beaujon
Clichy, France
NCT Number: NCT04007640
Obesity, diabetes and metabolic syndrome (MS) have all been associated with increase of pancreatic cancer (PK) risk. The precise role of obesity and diabetes and the pathways involved in the early oncogenic phases of PK associated with MS are not well known. The investigators hypothesize that it is possible to decipher this specific "fat-fibrosis-neoplastic sequence", to develop new imaging tools adapted to follow its progression, to test the benefit of treatments to slow this sequence and prevent the development of PK in obese and diabetic patients.This project is in line with a prevention strategy, by planning to understand the physiopathological pathways involved in MS leading to PK, to develop tools useful to screen early precancerous lesions in order to diagnose and treat patients at high risk, before cancer involvement.
This clinical trial is part of the INCA PAIR PANCREAS project : Early stages of pancreatic cancer associated with obesity and metabolic syndrome:
prevention and screening tools - Imaging of fatty pancreas in humans: correlation with pathological analysis, which includes 3 main coordinated objectives an in vitro approach an in vivo approach and this study (clinical approach).
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Notify Me18 year and older
All sexes
Interventional
Not applicable
Clichy, France
Translational approach with direct application to humans, to test specific imaging MRI sequences in obese patients.
Obesity and metabolic syndrome are a well-known risk factor of pancreatic cancer. Obesity is associated with about 30% increased risk in all studies, but the proportion of obese people varies considerably from one country to another. Therefore, the proportion of cancer attributable to obesity could range from 3% to 16%. Numerous epidemiological studies confirmed that obesity is a risk factor of pancreatic cancer in obese men and women (BMI, kg/m2≥30.0), with a relative risk estimated to 1.76 (95% CI, 0.90-3.45) and 1.70 (95% CI, 1.09-2.64), respectively. As previously demonstrated by partners 9 and 10, obesity is associated with fat pancreatic infiltration and precancerous lesions, such as PanIN lesions in humans. Pancreatic lesions such as adipose infiltration, iron deposits, extent of fibrosis, acino-ductal metaplasia and Pan-IN are involved in pancreatic oncogenesis.
The goal of this study is to be able to diagnose early precancerous states in patients, such as acino-ductal metaplasia (and also PanIN lesions which are more frequently observed in humans,) inflammatory process (iron deposits, fibrosis lesions) and adipose involvement in the context of obesity and metabolic syndrome. Investigators hypothesis is that specific MR imaging sequences, adapted from previous studies in rodents, could be a relevant tool to diagnose early pancreatic lesions and follow their evolution in the context of obesity and metabolic syndrome.
To this aim, the investigators will conduct a study to assess the relevance of MR imaging sequences to diagnose specific pancreatic lesions in obese patients, validated at the microscopic level. The investigators will analyze MR imaging of obese patients (BMI>30)/non obese patients (BMI<25) with a planned pancreatic surgery. It will be possible to compare imaging with histology performed on resected parenchyma. The investigators propose a proof-of-concept study aiming at assessing the relevance of specific MR imaging to diagnose early pancreatic lesions in humans and in obese patients especially. MR imaging will be performed in both obese and non obese patients with a planned pancreatic surgery in hospital to resect a benign lesion (such as neuroendocrine tumour or IPMN...). MRI are performed in the normal course of care; their sequences will be adapted for this study. It will be possible to compare imaging with histology of the resected parenchyma.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
For volunteers without history of known pancreatic disorders (1st stage):
For all participants (1st, 2nd and 3rd stages) :
MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences
MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences
Histological analysis :
Time frame: Day 1
Pancreatic fat content
Time frame: Day 1
Diffusion coefficients (10-4 mm2/s)
Time frame: Day 1
transverse magnetization relaxation rate
Time frame: Day 1
longitudinal relaxation rate
Time frame: Day 1
visco-elastic parameters by measure of tissue stiffness (kPa)
Time frame: 2 months
% surface of fibrosis
Time frame: 2 months
% surface of acinoductal metaplasia
Time frame: 2 months
number of acinoductal metaplasia lesions
Time frame: 2 months
% surface of fat pancreatic infiltration
Time frame: 2 months
% surface of iron deposit
Time frame: 2 months
% surface of fibrosis
Time frame: 2 months
% surface of acinoductal metaplasia
Time frame: 2 months y
number of PanIN lesions
Time frame: Day 1
pancreatic fat content
Time frame: Day 1
Diffusion coefficients (10-4 mm2/s)
Time frame: Day 1I
transverse magnetization relaxation rate
Time frame: Day 1
longitudinal magnetization relaxation rate
Time frame: Day 1
visco-elastic parameters by measure of tissue stiffness (kPa)
Time frame: 2 months
% expression of molecules involved in TGFb and orexin signaling
Time frame: 2 months
% expression of the markers in inflammatory cells (CD8, IL6, Caspase, HNF6)
Time frame: 2 months
% surface of acinoductal metaplasia
Time frame: 2 months
% of stained cells
Assistance Publique - Hôpitaux de Paris
Other
Early Stages of Pancreatic Cancer Associated With Obesity and Metabolic Syndrome: Prevention and Screening Tools - Imaging of Fatty Pancreas in Humans: Correlation With Pathological Analysis
Acronym: PAIR-PANCREAS
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