Pancreatic Cancer Margin Assessment in the Operating Room
Gibbs Lab: Contribution to pancreatic oncology surgery
Pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States. Over 44,000 people are diagnosed with PDAC in the United States annually, with an average life expectancy of 5 to 7 months post diagnosis. Treatment options for PDAC are limited, with surgical resection required for cure. Cancer cure is directly related to margin status, where the survival benefit of complete resection is established and incomplete resections are considered palliative at best. Even though only 10 to 15% of PDAC patients are eligible for surgical resection, complete resection with negative margins continues to prove difficult with positive margin status reported in as many as 15-85% of cases.
Current state of PDAC intraoperative margin assessment
Current surgical resections are performed without intraoperative imaging because targeted contrast for pancreatic cancer does not exist. Complete resection is assessed visibly and through palpation by the surgeon in the operating room. Real time assessment by the pathologist is completed through analysis of frozen sections of select pancreatic tissue margins during surgery. Unfortunately, many patients are left with residual disease from margins not assessed by frozen section analysis, false negative assessments, and microscopic metastases not visible to the naked eye at the time of surgery. All of these difficulties contribute to early cancer recurrence following what was thought to be a curative operation.
The Gibbs Lab is developing molecularly targeted contrast agents specific for PDAC
The Gibbs Lab is developing molecularly targeted contrast agents specific for PDAC that can be utilized in the operating room on resected pancreas tissue to evaluate margin status at the bedside. Our synthetic efforts are guided by the plethora of PDAC targeted small molecule therapeutics that have been developed, which largely do not result in lasting tumor response, but do bind to molecular targets in PDAC. We are developing therapeutic small molecule fluorophore conjugates with diverse fluorophores used for conjugation and with varied length spacers between the targeting molecule and the fluorophore. The binding affinity of the therapeutic small molecule fluorophore conjugates is quantified to determine the affect of fluorophore and linker length. Optimized therapeutic small molecule fluorophores conjugates will be tested in vitro, in vivo in mouse models and on resected ex vivo human pancreas tissues with the goal of fluorescence margin assessment in the operating room.