Widespread use of the resulting assessment tool can then improve shared understanding among clinicians and researchers of IA, facilitating advancements in care quality as well as further research. “I think the development of that instrument is going be critical to understanding the behavior of adhesions within the individual, purely from a clinical context,” Dr. Carmichael said.
The group also is exploring existing patient-reported outcome measures (PROMs) for adhesive disease with the goal of generating a definitive list for publication for both clinical and research use. “If we don’t know what it’s like to live with this disease process, then I think that we’re going to be lacking in our end points or outcome measurements,” Dr. Carmichael explained.
Dr. Maggard Gibbons detailed the PROMs the group has identified thus far: a list of symptoms including abdominal pain, pelvic pain, bloating, impairments in bowel function, symptoms of obstruction, food restriction, and disease-specific and general quality of life measures.
She noted, however, that this list is limited in its utility by the symptoms’ lack of specificity to IA. They overlap symptoms of the underlying health conditions, such as inflammatory bowel disease, cancer, and other gastrointestinal issues, that may exist alongside the adhesions and in fact may have prompted the operations that originally caused adhesions to form. (An analogous difficulty exists with respect to diagnosis of IA, where standard imaging and blood tests also offer insufficient clarity.5)
“It’s just hard because adhesions impact a lot of the disease processes, obviously,” Dr. Maggard Gibbons said.
Seeking Opportunities
The difficulty caused by overlaps continues in another key aspect of the work: the laboratory science defining IA physiology and the development of agents that can prevent or heal surgical adhesions in patients undergoing abdominal or pelvis surgery. Here, the issue is biological. The same mechanisms that permit wound healing after surgery are the ones that cause adhesions to form, and addressing adhesions therefore risks impeding wound healing. The possible complications include infection risk, an issue that has thwarted a number of medication-based management efforts. Valid methods of prevention and cure, then, must seek out the biological niches between the processes of healthy wound healing and fibrotic adhesion formation. This effort is made more challenging by an underlying physiological process that is not yet fully known.
“The things we don’t want is to make wound healing worse or make infection worse,” Dr. Carmichael said. “Where is the opportunity? From a biological standpoint, I’m not sure.”
The summit included multiple researchers delineating proposed preventative agents that had been shown not to work. Dr. de Wilde’s presentation, for example, listed nonsteroidal anti-inflammatory drugs, antibiotics, fibrinolytics, and corticosteroids as ineffective, with corticosteroids having particularly negative implications for infection and sepsis. He noted some clear mechanisms for ineffectiveness, including drugs not reaching or not remaining long enough at the relevant site, as well as drugs negatively influencing epithelization.
Although most summit attendees said they used barrier films for adhesion prevention while operating, Drs. Maggard Gibbons and Russell noted that existing products had mixed results. Their data suggested that Seprafilm (Baxter) is not associated with a lower rate of small bowel obstruction, while Guardix (Dongsung Chemical) is.
Most summit attendees had experience with and thoughts about a range of medical products. Outside of the event, researchers recently published research on interventions ranging from vitamin C supplementation6 to polyvinyl alcohol sponges7 to (in the case of Dr. Carmichael) human placental stem cell-based therapies.8 As a result, the SCAR Advisory Group has followed up by creating a systematic review and meta-analysis of clinically available prophylactic options for adhesive small bowel obstruction, with a particular focus on their effectiveness.
In addition, the group is creating a research paper that details the development of new technologies, Dr. Carmichael shared. Via an iterative process, it focuses on multiple considerations of prophylactic creation and challenges to biological and product development. The paper also will include inputs on regulatory science from a professional formerly with the US Food and Drug Administration.
Pursuing Laboratory Science
Finding further opportunities also will require the pursuit of scientific understanding of the physiology of adhesion formation and healing, as well as the biomedical engineering necessary to create efficacious interventions.
To that end, the Carlino Family, whose philanthropy was motivated by their son’s experience with IA, has provided funding for three grants of $100,000 each. These awards will be provided to scientists over 2 years for research projects exploring the biology of adhesive disease and/or the development of medical products that may provide means of prevention or cure.
There are many possible pathways for the scientists who are awarded these grants. Investigations may focus on the innate immune system, peritoneal mesothelial cells, and/or coagulation system that together can generate scar tissue and fibrosis across the peritoneal cavity. These studies may pursue insights into underlying genetics, the involvement of specific proteins, the role of inflammation, and much more. In addition to examining the complex physiological processes by which adhesions are formed, studies may focus on identifying specific targets for drugs to prevent or ameliorate adhesions, evaluating the performance of such drugs, and developing and assessing mechanisms of drug delivery.
Optimism
No matter the approach of these studies, there are many surgeons whose work will be informed by the project. “This is a quintessential shared experience if you operate in the abdomen,” Dr. Carmichael noted of encountering surgical adhesions—which means whatever strides forward are made will be applicable to many surgeons’ routine clinical practices.
Dr. Maggard Gibbons noted that change may not come quickly. “It does take a long time when you find something successful to put it into practice; that’s not a quick turnaround time. But to me, there was a lot of optimism at the summit that we can make improvements. We are hopeful about the future for this sometimes very chronic, debilitating problem for patients.”
