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US doctors report reconstructing new oesophagus tissue in a critically ill patient

Writing in The Lancet, US doctors report the first case of a human patient whose severely damaged oesophagus was reconstructed using commercially available FDA approved stents and skin tissue1. 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.

Until now, this regeneration technique has only been tested in animals. The authors, reporting on the outcome of the procedure, say that research, including animal studies and clinical trials, are now needed to investigate whether the technique can be reproduced and used in other similar cases.

Professor Kulwinder Dua from the Medical College of Wisconsin, Milwaukee, USA, and colleagues report using metal stents as a non-biological scaffold and a regenerative tissue matrix from donated human skin to rebuild a full-thickness 5cm defect in the oesophagus of a 24-year-old man. The patient was urgently admitted to hospital with a disrupted oesophagus resulting in life-threatening infection and inability to swallow following complications from an earlier car accident which had left him partially paralysed. Despite several surgeries, the defect in the oesophagus was too large to repair.

The oesophagus is a hollow muscular tube that connects the mouth to the stomach carrying food and liquids. Removal of the oesophagus (oesophagectomy) to treat cancer or injury 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. However, the procedure was not possible in this case because the defect in the oesophagus was too large, and the patient too ill to undergo the procedure.

The team hypothesised that if the three-dimensional shape of the oesophagus could be maintained in its natural environment for an extended period of time while stimulating regeneration using techniques previously validated in animals, oesophageal reconstruction may be possible.

They used commercially available, FDA-approved, materials to repair the defect. To maintain the shape of the oesophagus and bridge the large defect, they used an endoscope to place self-expanding metal stents. The defect was then surgically covered with regenerative tissue matrix and sprayed with a platelet-rich plasma gel produced from the patient’s own blood to deliver high concentrations of growth factors that not only stimulate growth but also attract stem cells to stimulate healing and regeneration. The sternocleidomastoid, a muscle running along the side of the neck, was placed over the matrix and the adhesive platelet-rich plasma gel.

The team planned on removing the stent 12 weeks after reconstruction, but the patient delayed the procedure for three and a half years because of fears of developing a narrowing or leakage in the oesophagus. One year after the stents were removed, endoscopic ultrasound images showed areas of fibrosis (scarring) and regeneration of all five layers of the oesophageal wall. Full recovery of functioning was also established by swallowing tests showing that oesophageal muscles were able to propel water and liquid along the oesophagus into the stomach in both upright and 45° sitting positions. But, how long the regeneration process took is unclear because the patient delayed stent removal for several years.

According to Professor Dua, “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.” 2