Impact of diagnostic peritoneal lavage on omentum metastasis

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PROJECT SUMMARY/ABSTRACT The omentum is an immune cell-rich fatty tissue that suspends from the stomach and plays an important role in peritoneal defense. The omentum is the predominant site of ovarian cancer metastasis, and metastasis to the omentum can lead to fatal bowel obstruction. Although surgical removal of the omentum has been advocated for cancer patients who do not present with overt omental metastasis, this prophylactic procedure has been contentious. The over-arching goal of this study is to identify approaches to minimize the risk of omental metastasis by occult circulating cancer cells when the omentum is preserved. Peritoneal lavage is a diagnostic procedure that is performed as part of abdominal cancer staging in which saline solution is administered into the peritoneal cavity and the washings are cytologically examined. Saline solution has also been widely used for i.v. fluid and electrolyte replenishment. Studies of infusion in the critical care setting have shown that the main adverse effect of saline solution is hyperchloremic acidosis, and there is evidence that acidosis can activate inflammatory responses that foster a cancer-permissive milieu. Because the omentum has immense capability to absorb fluid in the peritoneal cavity, we speculate that the omentum might be deleteriously affected by peritoneal lavage with saline solution. Based on these prior reports and our preliminary studies, we hypothesize that peritoneal lavage with saline solution stimulates the omentum to become conducive for implantation of occult cancer cells. In this study, we will evaluate the impact of peritoneal lavage with saline solution on cellular constituents of the omentum and inflammatory responses, and determine whether this lavage stimulates implantation of circulating cancer cells on the omentum in mouse allograft models of ovarian cancer. Importantly, we will also determine whether the risk of omental metastasis can be minimized by using buffered solutions instead of saline for peritoneal lavage. If successful, our study will provide a new and important rationale for revising diagnostic and staging practices to reduce the risk of metastasis to the omentum when this site is preserved.