'we Can't Leave Them To Suffer Alone'
Published by MAC on 2004-09-16Source: The Guardian
'We can't leave them to suffer alone'
Thousands of Britons are dying of a lung disease that has been largely ignored. James Meikle on the extreme surgery that may be the best way to treat a secret epidemic
The Guardian
September 16, 2004
There is a hidden killer out there. It will end the lives of more than 2,000 Britons a year in a terrible, painful way - and you may be only metres away from the cause, even as you read this.
It is called mesothelioma. For sufferers, it is a death sentence. But compared with diseases such as breast cancer, there is little in the way of public campaigning over the condition, or more than fractional funding of research into it. Now, surgeons are divided over a radical new solution, soon to be trialled. But it has raised an ethical question: is it better to conduct a major operation, which might lengthen life but risks killing the patient, or is it better just to ease the patient's passage to the grave?
The only certainty is the cause: asbestos. A mineral once seen as a natural wonder for its insulation and fireproof qualities, the stuff is everywhere in Britain: in our homes, schools, hospitals, workplaces. Properly sealed, it should be harmless, but if fibres become airborne and are then inhaled, the results can be disastrous. Asbestos is banned now, but more than 500,000 non-domestic buildings still have it.
The warning from cancer experts is that 100,000 people in the developed world will die a painful death, lungs constricted by an ever hardening lining. The symptoms (trouble breathing, unexplained chest pain), will have only started a few months before, but the tiny beginnings may have been laid 15, 25, even 50 years before. Exposure is usually occupational, in shipyards or building. But, increasingly, there are DIY casualties, or relatives who inhaled fibres while washing clothes.
The trouble is, no one is quite sure how mesothelioma develops. It may start when an inhaled fibre penetrates through to the mesothelial cells of the lung lining - known as the pleura. Macrophages, a type of immune cell, attack the inflamed tissue. Unfortunately, they are ill-equipped to deal with the fibre: they get damaged and spit the asbestos out. This process also damages the mesothelial cells of the pleura, which can start dividing uncontrollably and develop into a tumour pressing down on the lung. It's different to asbestosis - a better-known lung condition which comes from years of exposure.
For mesothelioma theoretically one fibre inhaled is enough to cause the damage. Blue and brown asbestos is thought to be the most dangerous, although white has also been linked. By 2015 to 2020, some 2,000 people in this country will be dying annually from mesothelioma, say specialists. In contrast, the Health and Safety Executive thinks that the peak may come earlier and be nearer 2,500. Other countries are expecting rising deaths, although the US may be past the peak because of earlier action against asbestos. In the developing world, where imports continue, the prognosis is grim.
David Waller, of Glenfield hospital, Leicester, says patients do not get referred to specialists such as himself be cause they are originally seen by non-surgeons, doctors who hold to "the generally held belief ... that this condition is untreatable". He adds: "Patients have been told by physicians in good faith, but in ignorance really, that nothing can be done for them."
The debate among the few doctors who specialise in mesothelioma is split between those who believe in radical surgery and those who favour more conservative options. The radical operation, extrapleural pnuemonectomy, involves removing the damaged lung and much that surrounds it.
Interest has surged, not least in patients informed by the internet, because of the work in the late 1990s of a Boston surgeon, David Sugarbaker. He reported survival figures of up to 48% at five years. Waller is a lead investigator in a pilot study, involving 50 patients, to be launched this autumn to assess the surgery. It will ultimately involve about 700 patients across Europe. Few surgeons in Britain now perform the operation. "I must probably do 70% of all the major operations for this condition," says Waller.
The surgery takes about three hours. Most tumours seem to be on the right side so the breast bone is split down the middle, and the whole lung is removed with its lining, the sac round the heart (the pericardium) and the diaphragm - the muscle between the lung and the abdomen. That is replaced with a prosthetic patch, as is the pericardium.
In the trial, patients will be randomised into receiving the surgery, chemotherapy and radiotherapy, or more minor surgery, chemotherapy and less radiotherapy. "The problem is going to be convincing patients to agree to be randomised. Some patients will have a clear idea they want surgery," he says. "We are not gung-ho. We turn down more patients than we operate on ... I tell them I can't cure them, right up front, because some of them come with unrealistic aspirations - that it is some kind of miracle surgery we are offering. It will come back in areas of the body I can't control by surgery. But our longest survivor is coming to four years from surgery, so we can offer a period of borrowed time they would not have otherwise, with a relatively good quality of life.
"I tell them to go and make the best of that time, and we have patients doing just that. They have cashed in insurance policies, and gone away to enjoy the last three or four years of their life rather than be told nothing can be done, they have to sit at home and wait for the grim reaper. I have a chap who climbed a mountain since he had his operation."
In a study Waller made of patients who did not have radical surgery, the average survival between diagnosis and death was six months "and, don't forget, that is not six months and then die suddenly but with a terminal phase of three to four months in pain, being slowly asphyxiated".
Others, however, are less enthusiastic about the operation. Andrew Ritchie, a surgeon at Papworth hospital, Cambridge, hopes to involve patients in the trials but says the results might not prove anything and that it will take years. "It is a big operation for which initial mortality was very high although over the last five to 10 years that has come down to more reasonable levels. But you always need chemotherapy and radiotherapy, too. It cannot clear the whole tumour out ... It is only suitable, if at all, for highly selected early-stage patients. Most are at late stage, frail and elderly and are no way ever going to be fit enough for an operation like that."
Ritchie says presentation does not always take decades. He has seen patients who have been exposed to asbestos only a few years before. "Making a diagnosis is extremely difficult even when a pathologist has tissue under a microscope. You can have benign conditions which cause excessive fluid in the lung cavity, causing shortness of breath. Other diseases are infectious. You don't want to give a patient a wrong terminal prognosis."
The palliative surgery he promotes offers an alternative to procedures dealing with fluid around the lung. Cells in a healthy lining produce small amounts of lubricant so the lung can expand during breathing without it catching on the chest wall. Disease causes either an overproduction of the fluid or stops it recycling as it becomes "a pleural effusion". The problem is common in mesothelioma, though not unique to it. "Tapping the fluid off by inserting a needle through the chest wall can give immediate relief but fluid rapidly accumulates once more," says Ritchie. Patients need repeated trips to hospital, and the treatment might actually help spread the tumour and introduce bacterial infection.
Doctors have tried to beat this problem by infusing talc in the hope that it can "stick" the lung up to the chest wall, but this too rarely works because the lung is bound by the tumour.
Ritchie devised a keyhole operation that is now to be measured in trials against the talc procedure. This is designed to deal with fluid and get the lung moving once more. It also removes parts of the tumour. He says this can be done in one hospital visit and is "suitable for the vast majority of patients who are elderly, frail and sick". "Patients live on average for 18-22 months when they would expect to die in four to nine months."
But it is extremely difficult to tell what stage of the disease patients are at, even after mesothelioma is diagnosed. All the patients involved in the keyhole procedure are "clearly pretty near the end of their journey", whereas those undergoing more radical surgery cannot be reliably placed, he says.
As the debate about surgery continues, national trials involving different types of chemotherapy are also under way. The received wisdom has been that none is very effective, but the newest arrival is not even involved in the comparative tests, partly because there was little known about it when the trials were prepared.
Pemextred, made by Eli Lilly with the brand name Alimpta, is licensed in the US and the company hopes to introduce it in Europe soon. Hopes have been raised for its use in conjunction with an existing treatment, and patients here already receive it on compassionate grounds.
Hilary Calvert, professor of medical oncology at Newcastle University and a consultant at Newcastle general hospital, was involved in a trial. Of the 25 who completed the study, eight responded to treatment with a large reduction in size of tumour. Of other patients who did not get 50% shrinkage, about 70% saw improvement in symptoms, less pain and improved breathing. Calvert has now treated about 100 patients with the drug.
Eli Lilly found median survival time increased by about three months. "That does not sound much, but nothing else had increased median survival time at all," says Calvert. "Some patients on it will survive for quite a few years. We have one who has survived for four or five. For something that is meant to be a lethal disease, that is quite a good result."
The drug stops cells dividing and its biology may make it more powerful still. "It is an analogue for folic acid, essential for the dividing of cells. It may be that Alimpta might be drawn into mesothelioma cells more rapidly than other cells. The tumour says 'Oh good, folic acid. I need that' and then realises it is more like a Trojan horse."
Will these new attempts to treat the disease be enough? Ken O'Byrne, former head of the British Mesothelioma Interest Group, who now works at St James's hospital, Dublin, is scathing about the lack of research money poured into the disease compared with, say, breast cancer. "People think it will pass away. It has often been perceived as a disease of older working-class men and historically they tend not to get the best deal."
The asbestos sub-committee of the all-party Parliamentary group on occupational safety and health wants a national strategy, says John Battle, Labour MP for Leeds West.
"Ten years ago, we were all saying 'You have HIV or Aids, you die.' Now, not only can we extend life, we can mitigate the worst effects so people don't suffer appallingly. With mesothelioma, people die a terrible death in agony. We can't leave them to suffer alone."