• Quantitative MRI parameters [ Time Frame: Day 1 ]
  Pancreatic fat content
• Quantitative MRI parameters [ Time Frame: Day 1 ]
  Diffusion coefficients (10-4 mm2/s)
• Quantitative MRI parameters [ Time Frame: Day 1 ]
  transverse magnetization relaxation rate
• Quantitative MRI parameters [ Time Frame: Day 1 ]
  longitudinal relaxation rate
• Quantitative MRI parameters [ Time Frame: Day 1 ]
  visco-elastic parameters by measure of tissue stiffness (kPa)
• fibroinflammatory lesions at histology in obese patients [ Time Frame: 2 months ]
  % surface of fibrosis
• fibroinflammatory lesions at histology in obese patients [ Time Frame: 2 months ]
  % surface of acinoductal metaplasia
• fibroinflammatory lesions at histology in obese patients [ Time Frame: 2 months ]
  number of acinoductal metaplasia lesions

• Histologic parameters [ Time Frame: 2 months ]
  % surface of fat pancreatic infiltration
• Histologic parameters [ Time Frame: 2 months ]
  % surface of iron deposit
• Histologic parameters [ Time Frame: 2 months ]
  % surface of fibrosis
• Histologic parameters [ Time Frame: 2 months ]
  % surface of acinoductal metaplasia
• Histologic parameters [ Time Frame: 2 months y ]
  number of PanIN lesions
• MRI parameters [ Time Frame: Day 1 ]
  pancreatic fat content
• MRI parameters [ Time Frame: Day 1 ]
  Diffusion coefficients (10-4 mm2/s)
• MRI parameters [ Time Frame: Day 1I ]
  transverse magnetization relaxation rate
• MRI parameters [ Time Frame: Day 1 ]
  longitudinal magnetization relaxation rate
• MRI parameters [ Time Frame: Day 1 ]
  visco-elastic parameters by measure of tissue stiffness (kPa)
• Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma [ Time Frame: 2 months ]
  % expression of molecules involved in TGFb and orexin signaling
• Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma [ Time Frame: 2 months ]
  % expression of the markers in inflammatory cells (CD8, IL6, Caspase, HNF6)
• Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma [ Time Frame: 2 months ]
  % surface of acinoductal metaplasia
• Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma [ Time Frame: 2 months ]
  % of stained cells

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.

• Radiation: MRI with additional sequences
  MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences
• Radiation: MRI
  MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences
• Procedure: Left pancreatectomy or pancreaticoduodenectomy
  Histological analysis :
• Radiation: MRI with additional sequences
  MRI with 15 min additional sequences to assess the relevance of MRI to diagnose specific pancreatic lesions in obese patients

• Volunteer patient
  1st stage: To adjust the transducer, test and validate pancreatic MRI sequences on volunteers without history of known pancreatic disorders. Adjustment of MRI parameters is needed to optimize data acquisition, especially in obese patients. Moreover, an external material (transducer) has to be applied on the abdomen. The right position has to be tested and specified before stages 2 and 3 of the study. We aim to include volunteers without history of known pancreatic disorders for the Stage 1, meaning volunteers without personal history or symptoms suggesting pancreatic disorders.
  Intervention: Radiation: MRI
• Obese volunteers with indication for hepatic MRI
  2nd stage: To validate and assess pancreatic MRI sequences on obese volunteers with indication for hepatic MRI , in relation with acceptable resolution and field of view criteria applicable to the typical anteroposterior diameters found in obese persons. For Magnetic Resonance Elastography (MRE), the amplitude setting of the MRE transducer will be adapted to the size of obese patients, in addition to the aforementioned adjustments to spatial resolution and field of view sizes. The effect of frequency on MRE data quality will be investigated. The effects of respiratory motion will be investigated; indeed in obese patients respiration amplitude is typically low and this enables to acquire data in free breathing mode over long periods of time, which offers more possibilities (notably in terms of averaging, spatial resolution, mechanical wave sampling rate) than when constraining acquisition parameters with a maximum breath hold time of less than 20s.
  Intervention: Radiation: MRI with additional sequences
• Obese patient
  3rd stage: To assess the relevance of MRI to diagnose specific pancreatic lesions in obese patients validated at the microscopic level. We will analyze MRI of obese patients and non-obese patients with a planned pancreatic surgery. It will be possible to compare imaging with histology performed on resected parenchyma
  Interventions:

  • Procedure: Left pancreatectomy or pancreaticoduodenectomy
  • Radiation: MRI with additional sequences
• Non obese patients
  3rd stage: To assess the relevance of MRI to diagnose specific pancreatic lesions in obese patients validated at the microscopic level. We will analyze MRI of obese patients and non-obese patients with a planned pancreatic surgery. It will be possible to compare imaging with histology performed on resected parenchyma
  Interventions:

  • Procedure: Left pancreatectomy or pancreaticoduodenectomy
  • Radiation: MRI with additional sequences

Inclusion Criteria:

• 1st stage : Volunteers without history of known pancreatic disorders

  - Adults

• 2nd stage : Obese Volunteers

  • Adults with planned hepatic MRI
  • Obese (BMI ≥30)

• 3rd stage : Patients

  • Adults (aged 18-65 years) with a planned pancreatic surgery for benign pancreatic lesions (IPMN, cystic lesions or neuroendocrine tumors)
  • Obese (BMI ≥30) or non-obese patients (18.5<BMI<24.9)

Exclusion Criteria:

For volunteers without history of known pancreatic disorders (1st stage):

- Symptoms or past medical history suggesting pancreatic disorders

For all participants (1st, 2nd and 3rd stages) :

• Patients with contraindication to MRI (pacemaker, claustrophobia…)
• Inability to undergo MRI due to weight excess
• Pregnant or breastfeeding woman
• Absence of free and informed consent
• Non affiliation to a social security regime or CMU
• Subject deprived of freedom, subject under a legal protective measure

• National Cancer Institute, France
• Ligue contre le cancer, France
• Fondation ARC