I've written before about abdominal adhesions — webs of fibrous tissue that bind internal organs together or to the abdominal wall. The adhesions are a surprisingly common post-surgical complication, affecting 50% to 90% of people who have undergone abdominal operations. Although most experience few — if any — symptoms, others suffer chronic pain, infertility, bowel obstruction and even death.
Despite the prevalence of these adhesions, there is no good treatment for the condition or way to prevent their formation. However, a team of Stanford Medicine researchers have discovered a technique that shows promise in laboratory mice.
Postdoctoral scholar Deshka Foster, MD, PhD; plastic and reconstructive surgeon Michael Longaker, MD; and pathologist Gerlinde Wernig, MD, have identified a molecular pathway involved in adhesion formation in mice and humans, and found that inhibiting the activity of a protein called JUN can substantially reduce the formation of adhesions in a mouse model. They published their results recently in Nature Communications
As Foster explained:
We learned that adhesions derive primarily from a thin layer of tissue that covers the bowel, called the visceral peritoneum. This explains why adhesion formation is often more severe following an open abdominal surgery rather than when a surgical procedure is performed laparoscopically. Furthermore, abdominal adhesions are formed by a locally-derived cell type (rather than cells recruited from another part of the body) called fibroblasts, which proliferate and differentiate to form a heterogeneous population. Finally, we identified a specific gene called JUN that is expressed by these fibroblasts in response to injury (such as a surgical procedure) and serves as a "master regulator" of adhesion formation.
The researchers found that over-expressing JUN in a mouse model of the condition caused the adhesions to be more severe; conversely, applying a small molecule that blocks JUN activity in the abdomen of the mice dramatically decreased adhesion formation after surgery. The scientists hope that a similar treatment may work to prevent the formation of adhesions in people undergoing abdominal surgery.
As Foster explained:
Clinically, our results are potentially quite exciting. Right now, there are not really any good options available to prevent adhesion formation after abdominal surgery. Further, if a patient presents with an obstruction from adhesions that does not resolve spontaneously, we have to intervene surgically and lyse the adhesions — but the surgery itself will ultimately end up causing additional adhesions to form.
Foster told me that the inhibitor that they used to prevent the formation of adhesions in the mice had already been explored in humans for the treatment of arthritis, and it had been well-tolerated.
Longaker said the team's next step is to try the process on a larger animal model.
"Post-operative intra-abdominal adhesion represent a huge problem that general surgeons struggle with everyday," Longaker told me. "It is my hope that the biology that we have uncovered in our mouse model will help us fast-forward to future treatments in humans."
Photo by Anut21ng Photo
