Preoperative Detection of Lymph Node Metastases in Pancreatic and Periampullary Carcinoma Using Ultrasmall Super Paramagnetic Iron Oxide Nanoparticle Ferumoxtran-10

Rationale:

Pancreatic ductal adenocarcinoma (PDA) is a devastating disease with a dismal prognosis which has not improved substantially in the past 40 years. A good preoperative TNM staging is of importance to determine the appropriate therapy and prognosis. An important negative prognostic factor is the presence of para-aortic lymph node metastases which are regarded as distant metastases and therefore precludes a curative resection of the tumor.

In only 33% of cases para-aortic lymph node metastases are detected preoperatively, due to the low sensitivity of CT and conventional MRI. Moreover, after a curative resection in 70% of patients liver metastases or a local recurrence of disease occurs usually in the lymph nodes of the mesenteric root and in the para-aortic lymph nodes. This suggests that at the time of surgery micrometastases in the liver and lymph nodes were already present. Determining lymph node status preoperatively, however, is a challenge. Ferumoxtran-10, an ultrasmall superparamagnetic iron oxide (USPIO) particle has proven to be a valuable contrast agent for detecting lymph node metastases using magnetic resonance imaging (MRI) in various types of cancer (also called nano-MRI). With this study we would like to validate the results of this technique with pathology in patients with pancreatic or periampullary (duodenal, papilla of Vater or distal bile duct) cancer, i.e. in all patients with adenocarcinoma in the pancreatic region. Ultimately improved preoperative staging of pancreatic and periampullary cancer leads to an improved treatment stratification plan. Demonstration of para-aortic lymph nodes could prevent an unnecessary operation with its associated morbidity and mortality and therefore improve quality of life. Additionally, if metastatic lymph nodes are present, it could complement image guided focal therapies on lymph node metastases such as radiotherapy.

Objective:

The first objective is to improve preoperative staging with 3TESLA (3T) NANO-MRI regarding the detection of lymph node metastases in patients with a pancreatic or periampullary adenocarcinoma when compared to a conventional contrast-enhanced CT with histopathology as gold standard. Other objectives are to improve a) the detection of liver metastases, b) the delineation of the tumor and c) the determination of local vessel ingrowth by the tumor. A more fundamentally oriented objective aims to detect "tumor associated macrophages" in a pancreatic carcinoma with an in vivo 3T NANO-MRI.