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|A Novel Therapy for Short Bowel Syndrome: Bowel Lengthening Device|
Farokh R. Demehri, MD, and Daniel H. Teitelbaum, MD
Short bowel syndrome (SBS) is a challenging disease that can have a life-long impact on patient health and quality of life. There is a high rate of mortality associated with SBS. Patients with SBS often require parenteral nutrition (PN) to maintain their nutritional status, and while PN can be life-saving, many infants as well as adults suffer from a number of PN-related complications. For patients who are unable to wean from PN, current treatment strategies include surgical lengthening of the small bowel, administration of growth hormones, and small bowel transplantation—all with widely variable results.
Mechanotransduction, or the conversion of mechanical forces into cellular signals, is an emerging area of research that may provide a novel treatment for SBS. With mechanotransduction, tissue growth is induced by applying mechanical force to tissues. These forces drive chemical cellular signals that stimulate the growth of cells and whole tissues. This principle has been described for well over a century. It has been applied in using a mechanical ratcheting device to help a shorter leg grow longer.
“Distraction-induced enterogenesis” is a term we use to describe the process by which the intestine lengthens with application of intraluminal linear forces (mechanical force applied lengthwise within the intestine). Through this process, the bowel not only lengthens, but the lengthened bowel demonstrates normal function as well. This has now been demonstrated in a number of animal models, including rats, mice, and pigs. A number of studies demonstrate that the lengthened intestine absorbs nutrients and performs peristalsis (to aid the passage of contents through the intestine) normally.
Our laboratory has spent the last decade developing a series of novel devices that can lead to such intestinal growth. This short article describes some of the goals for this process, and the challenges that must be addressed before it can be successful on a clinical basis.
Our laboratory has shown that patients with less than 10 percent of their normal intestinal length have a very poor chance of weaning from PN. We consider these patients good candidates for enterogenesis. Ideally, in addition to successfully creating enterogenesis in the patient, the device we develop will be implantable with minimal surgical intervention (e.g., endoscopic placement); safely attach to the intestine (couple to the inner lumen of the bowel); and uncouple from the bowel wall for easy removal.
We have used a young adult pig model for most of the work we’ve done in our laboratory. This model has allowed us to scale the size of the devices we’ve developed to the size that would be used in children or adults. Figure 1 shows the concept of one device implanted in a pig. Using a hydraulic device that we had implanted in the pig’s small bowel, we were able to achieve a 2- to 2.7-fold increase in intestinal length over a two-week period.
How does this hydraulic device work? We inject saline into the device through a tube brought outside of the pig. This fluid drives the hydraulic device to expand—much like the opening up of a telescope that has multiple tubes. We have been successful in elongating the bowel with this device. However, to date the work has typically involved at least two surgical procedures: one to implant the device and another to remove it. It is our goal to minimize surgery, as additional surgeries increase risk of surgical adhesions and infection.
Figure 1. Distraction-induced enterogenesis. In this experimental model, a curved hydraulic pump was implanted into an isolated segment of small intestine. Gradual hydraulic device expansion achieved up to 2.7-fold lengthening over two weeks.
While this device offers many improvements compared to our previous generation of devices, we still face several challenges. Our first is the need for a better and safer way to couple the device to the inner surface of the intestine. The second challenge is to improve our ability to measure how much force we are placing on the intestine during the process of enterogenesis. Too little force will fail to drive intestinal growth, while too great of a force will lead to intestinal perforation.
Future Directions and Challenges
Figure 2. Above: Fully endoluminal distraction-induced enterogenesis device. In this current model, two balloons are used to anchor the device to the inside of the intestine. This device can be implanted, extended, and removed via a stoma, allowing intestinal growth without additional operations.
External challenges will include clinical testing of this device for efficacy and safety. An even greater external challenge will be an economic one. Bringing such a device to market will not be easy. One of the greatest challenges we face is the fact that SBS is a rare disease. Attracting a company to partner with in the clinical development of this device has been quite challenging.
Bianchi A. Longitudinal intestinal lengthening and tailoring: results in 20 children. J R Soc Med 1997;90:429-32.