Healthy man has stomach removed

To avoid a rare genetic cancer, Oliver Grennell had his stomach removed. But a Kiwi surgeon is confident he can find a cure for the condition.

UNDER THE KNIFE: Christchurch man Oliver Grennell had his stomach removed after discovering he had a 70 per cent chance ...
DEAN KOZANIC/Fairfax NZ

UNDER THE KNIFE: Christchurch man Oliver Grennell had his stomach removed after discovering he had a 70 per cent chance of contracting gastric cancer.

For the next year Oliver Grennell is going to be the cheapest date around.

Despite being over six foot and until last month weighing 87kg, he can eat only small meals, and any alcohol goes straight into his system. That's because three weeks ago he had his entire stomach removed.

Grennell, 30, inherited a gene mutation from his father that meant he had a 70 per cent chance of getting gastric cancer - an elusive and fast-moving disease. The "total gastrectomy" will potentially save his life.

AFFECTED TOO: Isaia Piho, left, with daughter Tiare and wife Kelly. Isaia carries the mutation and has also had his ...
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AFFECTED TOO: Isaia Piho, left, with daughter Tiare and wife Kelly. Isaia carries the mutation and has also had his stomach removed.

The family history with stomach cancer was first recognised when a paternal uncle died from stomach cancer 10 years ago. Testing shortly before he died showed he carried a very rare genetic mutation which caused the cancer.

A look down the family tree revealed a number of other relatives had died of gastric cancer. The family is also part Maori - making them much more susceptible to carrying the gene mutation (doctors are unsure why Maori are more vulnerable).

When Grennell, his father and two brothers were genetically tested last year, all four were found to have the mutation (a one in 16 chance). They were left with little choice but to have major surgery to prevent the onset of cancer.

SERIOUS: Oliver Grennell in his hospital bed before the life-changing surgery.
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SERIOUS: Oliver Grennell in his hospital bed before the life-changing surgery.

His father had his stomach removed last August, Grennell had his operation in January, one brother had his gastrectomy a week later, and the third brother will have surgery later this year.

"It was a no brainer for me, because I am young, reasonably fit, I'd rather do it this age and adjust to a new normal, rather than risk getting a very aggressive cancer," says Grennell. "A 70 per cent chance of getting cancer is more than enough to make you choose the operation."

Twenty years ago the gene mutation was discovered by Professor Parry Guilford and his team in the Cancer Genetics Laboratory at the University of Otago. It was a huge medical breakthrough that allowed doctors to identify exactly which members of families suffering this cancer would be likely to get the disease.

The sudden advance happened when Guilford was contacted by the McLeods, a large Maori family in Mt Maunganui, who had been losing members to stomach cancer every year for decades. Despite folklore that a curse had been placed on the family, they realised that all the evidence - including very early onset of the condition - indicated the cancer was being caused by a genetic condition.

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In the wider New Zealand population, most sufferers develop stomach cancer in their 70s or 80s. The McLeods had family members as young as 14 years old who had developed and died of the disease.

Guilford started tests on the family in 1995, and by 1998 he was able to publish research showing the genetic mutation that caused the gastric cancer. In that time, his team found the mutation in two other Maori families, in the same gene.

"It was exciting because you can see a mutation in one family, and you can almost bet yourself that it's not real, it's just a strange one-off thing," says Guilford. "To find it in two more families, it made us completely certain we had the right gene. It was a breakthrough, and I hate using the word."

They discovered the mutation in a protein gene, E-cadherin, that acts as a tumour suppressor and has an adhesion role, holding the cells together and making them align themselves correctly.

They believe the mutation lets the cell break free from its normally highly regulated and controlled environment, and it starts to divide without the normal signs from neighbouring cells which keep them united.

"When they break out of that they start to divide, without those signals that say you shouldn't be dividing here, or moving this way, you start seeing other chance mutations in other genes and those cells which are in the wrong place start to proliferate very quickly and the cancer starts to grow really quickly," he says.

Recent developments have confirmed those with the mutation have a 70 per cent chance for men and 56 per cent for women of developing gastric cancer. Women with the mutation also have a 42 per cent risk of developing lobular breast cancer, a cancer difficult to detect by mammography.

The discovery has lead to the diagnoses of 16 families in New Zealand with the gene mutation (13 Maori), and overseas around 350 families have identified their family history of cancer as caused by the gene.

Around 180 members of the McLeod family have now been gene tested, and 60 identified as carrying the mutation. Around 40 chose to have their stomachs removed.

"If you have seen your mum die and a whole pile of cousins die and you are convinced you are going the same way, it affects your life choices," says Guilford. "You have not gone as hard as you might have getting a career, you might not have gone as hard as you might in putting yourself into relationships, you might not have gone as hard as you might looking after your finances.

"They immediately get set forth for a normal life."

Grennell is now adjusting to his new normal. The five-hour operation at Christchurch Hospital removed his entire stomach, a portion of his oesophagus and the upper section of his small intestine to ensure no potential cancer cells were left behind.

His oesophagus is now connected directly to his bowels via a 50cm length of the small intestine that was cut off and then attached to the duodenum, the upper part of the bowel. This intestinal limb at the join provides a section to stop the reflux of poisonous bile and pancreatic juice into the oesophagus.

Without his stomach, Grennell has to eat small and often. He bulked up in preparation for the operation, but in the two weeks after surgery, when he could eat only ice chips, he lost 7kg.

At the moment, careful not to cause internal damage, he's having six cup-sized meals a day. It takes him half an hour to drink 500ml of water.

Alcohol is out for now, and he has been advised not to drink spirits. When he is allowed a celebratory drink in eight weeks time, it will have a rapid effect.

"You will absorb everything you take more quickly as it goes straight from oesophagus into your bowel and it doesn't sit in your stomach," said Dr Ross Roberts, Grennell's surgeon.

Over time, a pouch will slowly develop at the join of the oesophagus and intestine, which will allow Grennell to eat regular meals. His father, nearly a year on from his operation, can now drink a glass of water at a time.

"You slowly introduce yourself into eating a little bit more, then a little bit more," says Grennell. "You could never go and get two Big Mac combos: you just don't have the capacity . . ."

His hunger has changed too. Hunger pangs come from both the brain and the stomach. "You don't get hungry, you get cravings," says Grennell. "The new hungry. I think it is a mental hunger rather than a stomach-rumbling hunger."

Without his stomach, the walls of which provided a valuable role in absorbing certain food and nutrients, Grennell has to follow a careful regime laid down by a dietitian. Vitamin B12, an essential nutrient to prevent anaemia and eventually death, is absorbed through the stomach walls. Grennell must have injections of B12 for the rest of his life.

He also doesn't absorb iron well without his stomach and has to be careful about eating too quickly, as his missing stomach once regulated the supply of food to the bowels.

But science is catching up on the genetic mutation. Through pre-implantation genetic testing, it is possible for couples to suppress the gene in their children through in vitro fertilisation (IVF).

After the egg has been fertilised by the sperm, and the embryo starts to divide, the cell can be tested for the mutation. An embryo that doesn't have the gene can then be chosen and implanted in the mother.

But chance mutations can occur in people who don't have a family history, and can be passed on without warning: "It will always be lurking around," says Guilford.

Guilford and his Otago team have spent the past five years developing a drug they hope will allow those who carry the gene mutation to suppress the cancer. He hopes that within 10 years, carriers will be able to take an annual or biannual dose that will kill early cancer cells, leaving the patient with just brief side-effects.

"What we are trying to do is kill off the early cancer cells, because they take quite a while to develop to be a lethal disease," he says.

A young girl has become the inspiration for Guilford's work.

Nineteen-month-old Tiare Piho's father, Isaia, carries the mutation and watched his mother die of stomach cancer. He has had his stomach removed.

Guilford has promised Tiare's family that by the time she is tested for the mutation when she is 16, she will not have to make the same decision as her father.

"Tia puts a face to what they do," says Piho. "They look at a lot of data, and a lot of information. To see a face, that is their information personified. That makes it a bit more real for them too."

He would love for his daughter not to endure the same process he faced. "It would definitely be a better option than having your stomach removed. It is safer and it is better for the health system not having a whole lot of people having their stomachs removed.

"If that is something that is six-monthly or annually, it makes life more manageable. The lives that it is going to save is awesome."

 - Sunday Star Times

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