Monitoring the gastrointestinal system for leaks after surgery can take several days in the hospital. In addition, this complication often isn’t detected until a series of intensive surgical interventions and a stay in the intensive care unit (ICU) is required.
Exero Medical Ltd. aims to address these issues with a wireless, biodegradable anastomotic leak sensor implant that is embedded into the surgical drain used after colorectal surgery. It has started a tiny five-patient, first-in-human study as a proof of concept for its technology. The first patient recently received the sensor implant at the Rabin Medical Center during low anterior resection surgery for rectal cancer.
The Or Yehuda, Israel-based startup plans next to conduct a larger, multisite safety study – and then after that a multicenter pivotal trial starting in 2021 that would potentially be sufficient to gain both U.S. FDA approval and a CE mark. After getting the technology through regulators in this initial indication, the next goal is to test the approach in bariatric surgery patients with an iteration of the product that could transition from the hospital to home use for the longer period of leak monitoring that these surgeries typically require.
“Most of these surgeries address removing a tumor from the colon. The GI tract is a tube and when the tumor has to be removed the surgeon usually cuts this tube and then he has to reconnect it,” Exero Medical CEO Erez Shor explained to BioWorld. “While he's able to verify during the surgery that this tube is properly reconnected, in up to 10% of the cases a leak begins several days after the surgery as a result of complicated physiological processes.”
“Nothing so far is really effective in preventing those leaks – not stapling technologies or all current glues, buttresses and sealants; nothing is really effective in preventing those leaks,” he continued. “So, an approach that was actually conceived by two doctors one is a surgeon and the other one is a biomedical engineer, was to actually enable early detection of those leaks, before they become a catastrophe.”
Exero is based on technology that was originally conceived of by Clalit HMO, the largest health maintenance organization in Israel. The company itself was founded in 2018 by the MEDX Xelerator, an Israeli Innovation Authority incubator and Clalit HMO. An early seed investment of less than $1 million took the startup all the way from an initial prototype into this proof-of-concept trial. The company hopes to raise additional funds to support further clinical testing based on these initial results.
The sensor is composed of undisclosed, biodegradable alloys. It is integrated into the surgical drain implant to monitor the health of the tissue around it to determine potential post-surgical anastomotic leakage, which is a common and potentially serious complication. Early detection can enable smaller-scale interventions, such as antibiotics or follow-up laparoscopic surgery to address the leak.
“We have biodegradable alloys that are both biocompatible and enable us to sense the electrical properties we wish to measure from the tissue, so that we can classify proper healing versus deteriorating conditions,” said Shor. “We measure some electrical properties of the tissue such as impedance; that is a good proxy for leak-driving conditions such as ischemia, inflammation and edema.”
“When the surgeon reconnects to the GI tract and sutures everything, the tube itself is sealed and is exactly airtight. In many cases, there is a local ischemic process that deteriorates,” he continued. “So, typically the leak-driving conditions begin with an ischemic hotspot and inflammation that then deteriorates into apoptosis, the death of cells, and eventually the perforation of this tissue. During this process, there is secretion of many stress factors; those can be identified if you have a local light sensor that is robust enough.”
Impedance is a measure of how electricity travels through a given material; each state and kind of tissue has different electrical impedance depending on its molecular composition. Data is transmitted via a small, wireless transceiver that is worn by the patient to record and transmit data wirelessly. It can be carried by ambulatory patients – and disconnected when the patient requires a shower. This data is the basis for information and alerts that are then provided to physicians and health care staff.
Shor noted that some early attempts at addressing this problem focused on the detection of biomarkers that were highly variable between patients, making it difficult to distinguish the trauma of major surgery from other subsequent issues with leakage in recovery.
He observed that once a patient develops a GI leak currently, that can lead to subsequent surgical and hospitalization costs in the range of $30,000 to $55,000. If the incidence is roughly 10%, then the average cost for every patient receiving this type of surgery is more than $3,000, with a global patient population that’s in the millions annually. Exero anticipates that its technology could offer a means for payers to curb those costs as physicians improve patient outcomes, thereby enabling a value-based approach to health care.
"The fear of anastomotic leak is the one that keeps GI surgeons up at night and one that represents a true clinical need,” said Nir Wasserberg, who is leading the ongoing proof-of-concept trial that’s being conducted at Rabin Medical Center. He is the chair of the Israeli Chapter of the Controlled Release Society, which facilitates tech transfer from academia to industry, and the director of its colorectal division. “Exero's sensor is designed to provide surgeons with insight on patients' healing processes so they can determine the best course of action and improve clinical outcomes."
The first human patient sensor placement was successful, including resulting data collection. The initial sensor is designed to function for up to a week, with surgeons expected to be able to allow an earlier release date for patients with no signs of potential problems. The upcoming bariatric iteration that it plans to develop would function for longer, since leak complications can occur even weeks after surgery. It would be accompanied by a wireless hand-held device that would collect the data at home and relay it to the doctor.
“Our technology can be used as a platform,” summed up Shor. “Once we're cleared for marketing our first indication for colorectal surgeries, we will be able to develop the version designed for bariatric surgeries. That capability to translate healing into tangible data will also be useful for additional indications in the future.”