By Richard Warry
BBC News Online health staff
The conjoined Iranian twins, Ladan and Laleh Bijani have died following hugely complex surgery to separate them.
Both twins wanted surgery
However, doctors always knew that the groundbreaking operation carried a high risk of failure.
Separating conjoined twins is tough enough at the best of times.
But there are two types that pose more difficulty for surgeons than any other - those who are fused at the heart and the brain.
Great Ormond Street Hospital in London has great experience at separating conjoined twins - but it has never attempted to separate children joined at the brain.
A spokesman told BBC News Online that the concept has only been theoretically possible for a short time.
Separating patients joined at the brain obviously poses risks
The major problem facing surgeons in this situation is to ensure that the blood supply to both brains is maintained at all times.
The brain is a very delicate structure and if it is starved of a blood supply for more than a few seconds, then brain damage is a distinct possibility. Much longer and death will soon follow.
Professor Lewis Spitz, has managed 23 sets of conjoined twins at Great Ormond Street. He also was a member of a team in South Africa in 1968 which successfully separated twins joined at the top of the skull and sharing a major blood vessel.
However, one of those children died six months after separation.
He said: "Separating patients joined at the brain obviously poses risks to the function of either or both brains.
"Some such cases will be easier than others, if not easy."
Professor Spitz said the chances of success would be highest if each twin had a separate blood supply to their brain.
However, this was not the case with the Bijanis.
"I cannot comment on the wisdom of proceeding with this operation but the media report that the patients were intelligent adults who were warned of the risks," he said.
The Bijani twins were fused at the head - making them what is known as craniopagus conjoined twins.
The twins as youngsters
Had the surgery been successful, they would have become the first pair of craniopagus twins in the world to undergo surgical separation as adults.
The surgery has been performed successfully since 1952 on infants, whose brains can more easily recover.
However, the twins posed a particularly tricky problem for two reasons.
First, they shared an important blood vessel, which drained blood from both their brains.
The vessel involved, according to neurosurgeon Dr Henry Marsh, is so delicate that damage can lead to a fatal stroke.
"You are playing with fire," he said.
And secondly, although their brains were separate structures, they had stuck together so tightly that detaching them posed huge difficulty for surgeons.
German doctors assessed the twins in 1996, but turned them away, deeming the operation to be too risky.
Doctors have a duty to act in the best interests of their patients, and in retrospect one is bound to conclude that maybe this surgery was misguided
The Singapore team agreed to go ahead after an exhaustive risk analysis, and after the twins had undergone extensive counselling.
First, they attempted to divert the blood vessel so that it served only one of the twin's brains, and to use a vein taken from the thigh to compensate for its loss in the second twin.
The surgeons successfully connected up the bypass vein, but it then became blocked, threatening the success of the entire procedure.
Doctors managed to clear the blockage, and added an extra shunt to further reduce congestion. This worked well.
Then to separate the brains, the neurosurgeons had to cut through the tissues very carefully. Among other things they had to tease out enmeshed nerve connections.
However, the surgery was further complicated by the fact that the blood supply between the twins was unstable, and surgeons had to deal with unstable blood pressure inside the two women's heads.
Both women lost a lot of blood during the 53-hour operation, but they appeared to tolerate the surgery well.
However, particularly heavy loss of blood occurred when the twins were finally separated.
Doctors tried to save the women by giving them emergency transfusions, but an hour after separation Ladan died. Her sister, Laleh died 90 minutes later.
The twins' chances of surviving surgery had been rated at 50:50 before their operation began.
Dr Richard Nicholson, editor the Bulletin of Medical Ethics, said in most cases the risk of death would be rated too high for doctors to proceed.
However, he conceded that imaging techniques were not sophisticated enough to allow doctors to know with precision how surgery would develop before they started.
"Doctors have a duty to act in the best interests of their patients, and in retrospect one is bound to conclude that maybe this surgery was misguided," he told BBC News Online.
"These twins were not suffering from a life-threatening condition, and although there were many things wrong with the quality of their lives, they had coped for 29 years."
Dr Nicholson also had concerns about the fact that it would have been impossible to brief each twin separately about the risks.
Thus, it was possible that one twin would have pressurised the other to go ahead against her will.
However, the Singapore team has stressed that both women were determined that surgery should proceed - whatever the risks.
A spokesman said: "We were told that Ladan and Laleh wanted to be separated under all circumstances.
"We knew the risks were great, but Ladan and Laleh knew it too. We were trying to do better than the worst odds, but alas we didn't make it."