Distal cholangiocarcinoma and pancreatic adenocarcinoma are aggressive cancers with overlapping diagnostic features, making them challenging to differentiate. Although both require similar surgical treatment, their postoperative chemotherapy regimens differ significantly, with capecitabine used for distal cholangiocarcinoma and modified FOLFIRINOX for pancreatic adenocarcinoma, based on distinct guidelines. In 10-20% of cases, due to their close anatomical proximity, pathologists cannot distinguish between these cancers, leading to diagnostic uncertainty and potential therapeutic missteps. Proteomic profiling, a cutting-edge technique leveraging protein analysis for diagnostic precision, could offer a novel solution to this challenge, although it has yet to be applied in this context

Distal cholangiocarcinoma (also known as biliary adenocarcinoma) and pancreatic adenocarcinoma are two aggressive cancers with numerous diagnostic similarities. They often present with nearly identical clinical features, tumor markers, and imaging findings on computed tomography (CT). Both cancers require similar surgical management-namely, a pancreaticoduodenectomy (also known as the Whipple procedure)-but their adjuvant systemic chemotherapy protocols in the postoperative setting differ significantly.

According to the French guidelines from the National Digestive Cancer Thesaurus, patients operated on for distal cholangiocarcinoma receive capecitabine as adjuvant therapy, while those treated for pancreatic adenocarcinoma receive modified FOLFIRINOX. These recommendations are based on randomized prospective studies that demonstrated improved overall survival and recurrence-free survival with these specific therapeutic regimens for each cancer. Thus, selecting the appropriate chemotherapy tailored to the cancer type is crucial for patient outcomes.

However, due to the close anatomical proximity of these two tumors-since the bile duct traverses the pancreatic head-it is estimated that in 10-20% of cases, the pathologist is unable to distinguish between these cancers. In such instances, the diagnosis is reported as "adenocarcinoma of pancreatobiliary origin." This ambiguity forces clinicians to choose a chemotherapy regimen based on a combination of clinical, radiological, and pathological findings rather than definitive histological evidence, thereby increasing the risk of an inappropriate treatment choice.

Proteomic profiling is an innovative analytical technique that enables diagnostic insights by analyzing the complete protein composition of a tissue sample and matching it to predefined profiles using statistical algorithms. While this method has already been successfully employed to aid in the diagnosis of other conditions-such as hepatocellular adenomas, amyloidosis, and biliary strictures of indeterminate origin-it has not yet been applied to differentiate pancreatic adenocarcinoma from distal cholangiocarcinoma.

Inclusion Criteria:

• Patients ≥ 18 years old
• Pancreaticoduodenectomy for pancreatic adenocarcinoma or distal cholangiocarcinoma
• Patient's non-opposition to the reuse of data

Exclusion Criteria:

• Neoadjuvant chemotherapy
• Patients under legal protection

10 patients with pancreatic adenocarcinomas, 10 patients with distal cholangiocarcinomas, 8 patients presenting pancreatobiliary adenocarcinomas with diagnostic challenges