For cancer patients, prognosis and treatment selection fundamentally rely on the staging assessment of the underlying cancer, i.e., determining the absence or presence of distant metastases. Despite improvements in the available staging tools, including cross-sectional radiographic imaging and laparoscopy, the accuracy of staging for gastrointestinal and gynecologic malignancies varies tremendously, with ?under-staging? considered as a common problem. Up to 30% of patients with these malignancies have distant recurrence of cancer shortly after major resections with curative intent; in the United States alone, this corresponds to about 15,000 patients per year. These recurrences, which often occur on the surface of the peritoneum, are thought to arise from the inability of conventional methods to detect small metastases (typically < 3mm) during initial staging. Our goal is to significantly improve the staging accuracy of peritoneal laparoscopy by increasing its capacity to detect such small, occult metastases. To achieve this goal, we will design and construct an optical accessory for standard laparoscopes, which will allow for polarized light imaging (Aim 1). Polarization-gating is a well- known technique to highlight surface features, and is thus expected to increase the detection sensitivity for superficial peritoneal metastases. This hypothesis will be tested by comparing the efficiency of standard versus polarization-gated laparoscopy for detecting highly scattering objects of well-defined size within tissue phantoms and cancerous cell clusters deposited on the surface of ex vivo animal peritoneal tissues (Aim 2). Finally, the feasibility and safety of polarization-gated laparoscopy will be evaluated in a small first-in-human study (Aim 3). The optical design of our accessory will rely on a removable sleeve with external optical filters at the distal end of the laparoscope, to linearly polarize the white light used to illuminate the peritoneum. At the proximal end, a half-wave liquid crystal retarder will allow for automated, near video-rate collection of images polarized in either parallel or perpendicular geometries relative to the polarized light incident on the peritoneum. The sum of these orthogonally-polarized images can be used to reconstruct standard laparoscopy images, while their difference is expected to show enhanced contrast for observing surface features. To characterize the sensitivity of this approach, we will first perform studies using tissue phantoms that will enable us to identify the scattering contrast, size and depth characteristics of features that can be detected and the corresponding levels of detection enhancement using polarization. Ex vivo studies will be performed on exposed peritoneum of normal rats on which small cancerous cell clusters (sub mm-3mm size) are deposited to confirm our in vitro findings. Finally, we will conduct a limited study (10 patients) to assess feasibility and safety of differentially-polarized light laparoscopy for detection of peritoneal metastases in adult patients with gastrointestinal or gynecologic malignancies. Based on very preliminary ex vivo human tissue measurements, we expect a nearly two-fold contrast enhancement using our device compared to standard laparoscopy.
to Public Health: These studies will establish a robust, yet simple method to improve the staging accuracy of standard laparoscopy via the detection of occult peritoneal metastases. This will significantly lower the incidence of post- operative cancer recurrences in patients with certain gynecological or gastrointestinal cancers, by better identifying those who would truly benefit from operative treatment versus those who would be better served by additional intra-peritoneal chemotherapy.
