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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
59
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 :
MRI with 15 min additional sequences to assess the relevance of MRI to diagnose specific pancreatic lesions in obese patients
Hôpital Beaujon
Clichy, France
NOT_YET_RECRUITINGHôpital Beaujon
Clichy, France
RECRUITINGQuantitative MRI parameters
Pancreatic fat content
Time frame: Day 1
Quantitative MRI parameters
Diffusion coefficients (10-4 mm2/s)
Time frame: Day 1
Quantitative MRI parameters
transverse magnetization relaxation rate
Time frame: Day 1
Quantitative MRI parameters
longitudinal relaxation rate
Time frame: Day 1
Quantitative MRI parameters
visco-elastic parameters by measure of tissue stiffness (kPa)
Time frame: Day 1
fibroinflammatory lesions at histology in obese patients
% surface of fibrosis
Time frame: 2 months
fibroinflammatory lesions at histology in obese patients
% surface of acinoductal metaplasia
Time frame: 2 months
fibroinflammatory lesions at histology in obese patients
number of acinoductal metaplasia lesions
Time frame: 2 months
Histologic parameters
% surface of fat pancreatic infiltration
Time frame: 2 months
Histologic parameters
% surface of iron deposit
Time frame: 2 months
Histologic parameters
% surface of fibrosis
Time frame: 2 months
Histologic parameters
% surface of acinoductal metaplasia
Time frame: 2 months
Histologic parameters
number of PanIN lesions
Time frame: 2 months y
MRI parameters
pancreatic fat content
Time frame: Day 1
MRI parameters
Diffusion coefficients (10-4 mm2/s)
Time frame: Day 1
MRI parameters
transverse magnetization relaxation rate
Time frame: Day 1I
MRI parameters
longitudinal magnetization relaxation rate
Time frame: Day 1
MRI parameters
visco-elastic parameters by measure of tissue stiffness (kPa)
Time frame: Day 1
Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma
% expression of molecules involved in TGFb and orexin signaling
Time frame: 2 months
Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma
% expression of the markers in inflammatory cells (CD8, IL6, Caspase, HNF6)
Time frame: 2 months
Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma
% surface of acinoductal metaplasia
Time frame: 2 months
Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma
% of stained cells
Time frame: 2 months
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