Reconstructing new oesophagus tissue in a critically ill patient

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In the latest example of scientists creating body parts in the lab to help patients with little options, American doctors have made a new oesophagus for a young man, using donated skin tissue and metal stents. This case was reported in The Lancet.

Seven years after the reconstruction and 4 years after the stents were removed, the patient continues to eat a normal diet and maintain his weight with no swallowing problems.

The doctors struggled to repair the oesophagus of this 24-year old man, who was paralyzed in a car crash 7 years ago. The general practice is to make a new one using a tube from the patient’s own digestive system. However, that wasn’t possible due to the nature of the man’s extensive injuries.

esophagus 2
Oesophagus is the part of the alimentary canal which connects the throat to the stomach (http://bit.ly/1SZ1qWu)

Instead, doctors decided to try a regeneration technique previously tested only in dogs, to reconstruct the upper esophagus with stents and skin tissue approved by the U.S. Food and Drug Administration. The researchers, however, suggest that extensive animal studies and clinical trials are still required to reproduce this technique in other similar cases.

The oesophagus, commonly known as the food pipe or gullet, is an organ in vertebrates which consists of a fibromuscular tube through which food passes, aided by peristaltic contractions, from the pharynx to the stomach. Oesophagectomy (partial or complete removal of the oesophagus) is a routine practice to treat cancer or injury. This requires reconnecting the remaining part of the oesophagus to the stomach to allow swallowing and the passage of food. Part of the stomach or colon is used to make this connection.

Professor Kulwinder Dua from the Medical College of Wisconsin, Milwaukee, USA, one of the authors of the study reported that the team used metal stents as a non-biological scaffold and a regenerative tissue matrix from donated human skin to rebuild a full-thickness 5 cm defect in the patient’s oesophagus. Their hypothesis stemmed from previously validated oesophageal reconstruction studies in animals. They planned on generating a structure that could mimic the three-dimensional shape of the oesophagus in its natural environment for an extended period of time. This was then coupled with stimulation of regeneration techniques.

Physicians inserted an endoscope containing a wire through the man’s stomach and up through what remained of his esophagus, leading to his mouth. Guided by the wire, they then inserted three stents to recreate the structure of the esophagus and covered it with skin tissue. The tissue was then sprayed with a gel made from the patient’s own blood, which contained natural substances to attract stem cells.

Although the doctors wanted to remove the stents about 12 weeks after the surgery, the patient refused, fearing he wouldn’t be able to eat and drink. He was also worried about possible scarring. Nearly four years later, doctors removed the stents after the man had trouble swallowing when a problem arose with the lower stent.

One year after that, doctors examined the man’s esophagus and found that all five layers of the esophagus had regrown, closely resembling a normal one. Full recovery of functioning was also established by swallowing tests. The patient hasn’t needed a feeding tube and hasn’t reported any other complications. But, how long the regeneration process took is unclear because the patient delayed stent removal for several years.

“We initially thought (the results) were too good to be true,” said Dr. Kulwinder Dua, who led the surgery. “But the proof in the pudding is that this guy is now eating and drinking normally.” According to him, “This is a first in human operation and one that we undertook as a life-saving measure once we had exhausted all other options available to us and the patient. The use of this procedure in routine clinical care is still a long way off as it requires rigorous assessment in large animal studies and phase 1 and 2 clinical trials. The approach we used is novel because we used commercially available products which are already approved for use in in the human body and hence didn’t require complex tissue engineering.”