Journal of Pediatric Surgery Article Review: February 2022 - BAPS Issue

Dr. Adrian Wolf's research focuses on creating renal organoids with glomerular differentiation from pluripotent stem cells to model human genetic kidney and urinary tract diseases and potentially grow a whole new renal tract.

Organoid tissues could potentially be used as replacement therapy instead of formal kidney transplant and could one day be functionally useful in a living patient.

The research approach involves identifying the gene that's gone wrong in children born with abnormal kidneys, making stem cells from their blood samples, growing organoids in culture to reproduce the disease in a dish, and looking for druggable targets.

Growing a ureter is difficult, and without the ureter, even if a little kidney could make urine, the urine would have nowhere to go.

The very small size of these tissues (a few millimeters across) means that if used as renal replacement therapy, hundreds of them would have to be implanted into a person.

These little kidney organoids cannot be connected to a big artery, and the glomeruli in them could never really make much urine because they wouldn't have high pressure, high flow going into them.

Organoids are going to be the big technology of the next decade.

The results of ELBT are variable - in some babies it works really well and brings the esophagus together when it's going to be difficult, and in other babies it doesn't always work so well.

In babies where ELBT doesn't work well, all managed to have a cervical esophagostomy and survive, with reconstruction typically using gastric transposition.

There were three deaths after anastomosis in the UK ELBT series.

ELBT is not universally successful and its role in the management of long gap esophageal atresia will still remain controversial.

The Netherlands is a small country with only 17 million people, with about 30 to 40 cases of esophageal atresia per year across 6 pediatric surgical centers.

Centralization in the Netherlands was a gradual process starting in 2014 with oncology procedures, expanding to abdominal and thoracic and head and neck cases in 2015, and neurosurgical and orthopedic oncology in 2018, with every oncological diagnosis now done in Utrecht.

Of the remaining 5 pediatric surgical centers in the Netherlands, only 1 hospital is now doing biliary atresia and choledochal cysts.

Esophageal atresia cases are only done in 3 hospitals in the Netherlands, and anorectal malformations and Hirschsprung are done in 4 hospitals out of 6.

In the United States, having single centers for rare procedures like in the Netherlands would not be feasible due to the much larger size of the country.

The reimbursement system in the United States is different - physicians are reimbursed on volume - making centralization not an easy thing to do, with a degree of resistance within centers to giving up what is a major part of practice.

Results improved dramatically with centralization - not just because two surgeons got together and were better at it, but because they operate together and operate more often, with the Utrecht center doing about 30 neuroblastomas and 35 renal tumors per year.

When medical device equipment breaks in developing nations, local staff often don't know how to fix it.