Researchers from the Medical College of Wisconsin are reporting the first human case of esophageal regeneration in a man whose esophagus was destroyed following complications from an earlier automobile accident.
As explained in the article published online in Lancet on April 8, the paralyzed patient had undergone spinal plating immediately after the accident, but several years later the plate became infected and the patient developed a mediastinal abscess, resulting in a 5 cm esophageal defect that made it impossible for him to eat and threatened his life.
The defect was too long for end-to-end repair and the patient was too sick for formal pull-up or esophageal replacement procedures, Kulwinder Dua, MD, told Medpage.
He had undergone many surgeries, but the surgeons were unable to fix this very large defect, so they eventually called us and asked us if we had any bright ideas," Dua said. "This patient was in a life-threatening situation.
With few other options, Dua and colleagues initially used a self-expanding metal stent (diameter 18 mm, length 120 mm) as a non-biological scaffold to bridge the 5 cm deficit. The stenting was surgically covered with regenerative tissue matrix and sprayed with platelet-rich plasma gel derived from the patient's own blood to promote tissue growth.
A month later, the stent needed to be removed due to migration, and it was replaced by three stents that were telescopically aligned to improve anchoring. The patient was able to drink and eat soft foods soon after this procedure.
The team had planned to remove the stenting within three months of reconstruction, but the patient delayed the removal for more than three years due to fears of esophageal narrowing or leakage.
After the stent was removed, the patient was assessed using endoscopy, biopsy, endoscopic ultrasonography, and high-resolution impedance manometry.
The imaging revealed full-thickness regeneration of the esophagus with stratified squamous epithelium, a normal five-layer wall, and peristaltic motility with bolus transit, the researchers wrote. Four-years after stent removal, the patient was eating a normal diet and was able to maintain his weight.
Testing confirmed the full recovery of functioning, showing esophageal muscles that were able to move water and liquid along the esophagus into the stomach in both the upright and 45°-sitting positions.
The researchers were not able to determine how long it took for regeneration to occur, however, because stent removal was delayed for several years.
We showed that full-thickness long-segment defects in the human esophagus can be treated with regenerative medicine approaches that have so far been tested only in animals, Dua and colleagues wrote.
They noted that esophageal regeneration has the potential to improve the quality of life of cancer patients requiring esophagectomy, who are at high risk for complications from gastric pull-up conduit procedures. It could also potentially be used in other conditions, such as the congenital condition of esophageal atresia, that require gastric pull-up conduit procedures.
But the use of the procedure in clinical practice is years away, following additional animal studies and phase I and II trials, Dua told MedPage Today.
He noted that the procedure was performed to save the life of a patient with no other options and that there are no plans to attempt the procedure in other patients anytime soon.
We are going back to animals first," he said. "This is just one case, and we have a lot to learn.
In an editorial published with the study, Martin Birchall, MD, of the Royal National Throat, Nose and Ear Hospital, London, and Paolo De Coppi, MD, of the University College London agreed that much work needs to be done before the procedure is tried again in humans.
Despite this success, additional testing in preclinical models remains essential, although individual components of the technology have been reported previously and are reviewed by Dua and colleagues, they wrote. "Additionally, extracellular matrix and platelet-rich plasma have regenerative potentials that are related to their angiogenic and immunomodulatory properties.
The editorial concluded that reverse translation should drive this group and others to test the hypothesis generated by this clinical success.
Source: Medpage, DWN Africa
: 2016-04-11 18:54:07 | : 1298