Tom Treasure Weblog

As the end of the year approaches it is time to plan for next year. I have just attended a series of meetings about meetings. ESTS Council met in Paris to plan the May 2006 Cluj-Napoca meeting, EACTS discussed the Stockholm meeting in Windsor and in London we are setting the programme for the Summer meeting of our Cardiothoracic Section of the Royal Society of Medicine. For 23rd June 2006 the subject at the RSM is The Cardiac Multidisciplinary Team. This is the notion that the cardiologist and surgeon work together to decide the coronary management plan. Perhaps the public think that happens already but evidently not. Read David Taggart (Professor of Cardiovascular Surgery in the University of Oxford). Taggart reasons that “A multidisciplinary approach is essential” (BMJ 2nd April 2005). More often in my experience the patient is shown a coned-in view of a narrowed coronary artery, there is some physicianly body language in the form of head shaking, brow furrowing and sucking in through the teeth, and then, hey presto, have I got the stent for you! The solitary man with a hammer sees a nail and knows what he has to do - but from the wider perspective of a multidisciplinary team, each intervention is only one step on the patient’s life journey in which a single step driven by the occulo-stenotic reflex might just be a step in the wrong direction. Surely that first step should not be made without consideration of the route ahead and the ultimate destination. For many patients now receiving percutaneous coronary interventions (PCI) if all aspects were properly considered “best evidence favours surgery over percutaneous intervention” writes Taggart and he ably defended his argument in debate at EACTS (Barcelona September 2005) and again in the correspondence columns of the British satirical magazine Private Eye.

Life defining decisions about coronary interventions are important enough to be made in a Multidisciplinary Team Meeting.

Surgeons joke about the occulo-stenotic reflex and yet the most eminent cardiologists use before and after slides to make their point, as they have done since the first PTCA. Now it’s a video clip rather than grainy stills but this salesman’s “now you see it now you don’t” approach is surely demeaning to a senior audience who deserve data. To make a decision we need statistically sound results in hundreds and thousands of patients, and to know relative benefits in terms of years and decades, in comparisons with other or with no intervention. You can hear more from David Taggart along these lines at meetings to come - and it should be worth hearing. Meanwhile he is adding to high quality evidence with his brain child the Arterial Revascularisation Trial (ART) (http://www.csm-oxford.org.uk/index.asp?o=1121) which compares single versus double mammary artery grafting. Multivariate analysis, however brilliant the analyst, will not resolve whether the claimed long term benefits are attributable to the second mammary graft itself or the potential confounders which are its selected application in better patients and the higher degree of skill required for a surgeons to be comfortable with this choice. The point is that an RCT is the only way to find out. It is hoped that Taggart’s ART trial will answer the question; it has already recruited about 700 patients!

The management of coronary disease is a remarkable international success story which I have seen unfold in my professional lifetime. It has been both a technical and public health triumph. Soon after the Argentinian surgeon Favaloro visited London in 1970 and demonstrated his coronary operation, I assisted Donald Ross with some of the first coronary operations in England. Through the 1980s I supported our cardiologists as they replicated the angioplasty work of the Swiss radiologist Gruntzig and into the 1990s I participated in the British RITA trials. Very many patients have been helped by these interventions but the down turn in the coronary disease epidemic which we are now seeing has been gained neither by surgery nor PCI. It is due to substantial changes in consumption of fat and dairy products, cholesterol lowering by diet and pharmacology, and because smoking is going out of fashion. Those benefits gained in populations, also inform the multidisciplinary team (MDT) approach which plans not only the interventions but drives metabolic and life style change for the individual.

For the thoracic surgeon the equivalent epidemic has been lung cancer where the incidence is also turning down thanks to a public health mission against smoking but for the many lung cancer patients we will continue to see, multidisciplinary working is the norm. In the UK the MDT is now the standard of care. We have at our disposal chemotherapy, radiotherapy, surgery and a range of palliative strategies and the challenge is to employ whatever combination will give the patient the best prospect of relief and longevity. And that is what we do. I am pleased to have been brought up and to have trained within a health service where we do not compete to treat and bill (pace Dr Replogle’s blog “Blind Faith and Choice 27th November). There is an important and unstated difference however between the pulmonologist and the cardiologist. The pulmonologist is the usual first point of contact for lung cancer patients, the “gatekeeper” and, in our team at Guy’s Hospital, he is the leader. But the respiratory physician does not “treat” the cancer, in most instances. Clinical management – chemotherapy, radiotherapy, surgery or any combination - is in the hands of other members of the team. This is in marked contrast to angina where the cardiologist is not only the gate keeper but prescribes all the drugs, adjudicates on all the tests, performs the angiogram and, like the man with a hammer to whom everything looks like a nail, the cardiologist can and will perform the PCI. Surgery tends to be a last resort when all else has failed.

For coronary disease there is a whole other context which is the management of acute coronary events, particularly evolving infarction. Howard Swanton recent President of the British Cardiac Society presented the evidence for the relative merits of PCI and thrombolysis at the Evan Jones Memorial Lecture at St Thomas’ Hospital (November 2005). Just as the elective management of angina has been completely transformed in my lifetime, so have the options for acute ischaemia. In the 1960s patients with infarcts were put to bed and kept there. In 1967 I remember presenting such a patient to an austere physician and had the misfortune to use the phrase “coronary thrombosis”. He had a gaze that shrivelled medical students and turning it on me he asked “Where do you learn your medicine, Treasure? In the Reader’s Digest?” for it had been proven and was well known to him and apparently the rest of the world in the 1960s that infarction was not caused by thrombosis in the coronary artery. That was before GISSI, ISIS2 and the benefits of chewing an aspirin rescued the thrombus theory from being a figment of my imagination to its now central role. Also it turns out that the sooner you restore blood flow, the more likely you are to live and the more myocytes you will have with which to enjoy life - hardly a surprising “discovery”.

Early in my career, emergency surgery was tried and set to one side. Now if my anterior descending coronary were to occlude and I could get to Dr Swanton, or even someone half as skilled, that’s what I would want: acute PCI. I had the pleasure to work with him between 1982 and 1990. In those years the emphasis was that the emerging technology of angioplasty should be “safe” and always be backed up by surgery. Attention was focused on stable angina and the “culprit lesion”. Infarction is often the very first manifestation of coronary disease and it is the mild stenosis, that fissures and occludes, that may well be the fatal one (Lancet 1991; 338:1379-80). The occulo-stenotic reflex produces an undue emphasis on stenoses. Which will be the one to occlude and when, we cannot predict. When a vessel occludes, the culprit has declared itself and the object is clear – to reopen it to save heart muscle and to save life – and 24/7 catheter laboratory availability will be needed to deliver that service. On the other hand, for an elective case, a planned surgical strategy of complete revascularisation including arterial grafts may be a better strategy for life than picking off one stenosis after another in the catheter laboratory. That is a decision that deserves an MDT.

Posted by Tom Treasure at 07:02 AM | Permalink

Over the past few years, this question has become more pressing, both for the profession and for me as a surgeon. However long and hard I look at the problem I come to the same conclusion – we need a proper controlled trial.

For the twenty years until 2001 did a very broad range of work as a cardiothoracic surgeon. My cardiac surgery, in addition to the full range of elective and emergency surgery for ischaemic and valvular heart disease, included an increasing tertiary referral practice in aortic surgery and a period of some years in transplantation. Consequently in thoracic surgery, to somewhat limit my range, I left oesophageal surgery and chest wall reconstruction, for example, to full time thoracic colleagues. As for Mesothelioma, it was rare when I started and I was content to see the few cases that came along go to the pure thoracic surgeons for an opinion. Now two things have changed. Mesothelioma has become much more common and, having been invited back to Guy’s Hospital, my alma mater, as a General Thoracic Surgeon, I have had to take a position on this challenging problem.

The problem: Mesothelioma now kills more people a year than either melanoma or cancer of the cervix. The death rate will rise for 10-15 years. About 60,000 new cases are projected in the UK over the next 45 years. The same is true in Europe. The epidemic may be declining in the USA but in many countries in Asia and South America asbestos is still uncontrolled and there is bound to be a huge burden of illness.

Is there any hope of cure? Extrapleural pneumonectomy (EPP) promulgated in the 1970s by the British surgeon Eric Butchart is the radical surgery on offer in which the parietal pleura, mediastinal pleura, pericardium and the diaphragm are taken en bloc with the lung inside the envelope. If surgery alone had a self evident role it would probably have been established by now – or would it?

An historical digression: Consider the history of mitral valvotomy for rheumatic mitral stenosis. In the 1940s the proposed operation of valvotomy was authoritatively declared to be not only dangerous to the point of recklessness but also misconceived since any physician knew that it was the myocardium that was the problem; the stenosed valve was a non-contributory epiphenomenon. Within a few years of Bailey, Harken and Brock’s operations in 1948 it was universally accepted. Surgery had been first proposed fifty years earlier in 1898. It took fifty years to become established (Treasure T, Hollman A. The surgery of mitral stenosis 1898-1948: why did it take 50 years to establish mitral valvotomy? Ann R Coll Surg Engl 1995; 77:145-151).

The case for EPP: The best survival has been reported by David Sugerbaker in a subset of 31 patients who had three prognostically significant variables: epithelioid cell type, clear resection margins, no positive extrapleural nodes (JTCVS 1999). Their median survival was 51 months. No reference population anywhere has survival figures with a median in excess of four years. On the strength of these results, Sugerbaker’s team offer patients who meet these criteria radical surgery preceded usually by chemotherapy and followed by radical radiotherapy. Not to do so would be to deny 50% the chance of cure. They add weight to their case for EPP (or weaken it, depending on one’s point of view) by adding an argument ad hominem, accusing the other side (and this is an issue where sides are taken) of therapeutic nihilism and surely nihilism in this and all cancers must be a thing of the past?

The case against EPP: To perform EPP is to base a lot on just 31 patients retrospectively selected. It may all be a consequence of retrospective exclusion of the patients with unfavourable features. Let me explain. If one establishes favourable features from a data base, and redefines the groups on the basis of significantly favourable and unfavourable features, there will be a difference in favour of the better group. That is a statistical inevitability, leading to a circular argument. That is why in developing a risk model the data are randomly divided into a first test set to devise the risk model and the remainder are used to test its reproducibility.

Is it likely that the results will be replicated prospectively? Let us look at that again in clinical terms. You have identified the favourable features for longer survival. You do not operate on those without favourable features and confine your efforts to those most likely to survive. You then look at survival for the selected group operated on. They will probably do less well than the artificially selected group in the retrospective analysis but they may well do better than historical controls. But the historical controls are dominated by the very sort of cases that you elected to not operate on. Again, it becomes circular and self-serving, say the doubters.

Like those in favour, those against EPP seek to bolster their arguments with emotive language, answering the charge of therapeutic nihilism with references to quality of life. They emphasise the inescapable fact that trimodality therapy will take six to nine months. Perhaps it is inhumane to use up the best remaining months of someone’s life this way.

The basis of equipoise: So this is the situation I found as I took up my tools as a born again general thoracic surgeon. Which policy to adopt? The disease was becoming more common and we were diagnosing cases ever more frequently, sometimes several a week. Which camp was I in? Either way I faced a personal problem of integrity. Could I, as a sceptic, deny active treatment without the evidence to back up that decision or, as an enthusiast put patients through extreme treatment on a judgement made outside the evidence? Whichever of these two opposing views is espoused, and however well intended, the evidence is simply not there to support either. Are we entitled to a free for all, each side engaging in highly charged rhetoric?

My colleague Jules Dussek invited me to a meeting of his European Thoracic Surgical Club in 2001 soon after I joined him at Guy’s. On the programme was the Italian surgeon Maggi who related his EPP experience. Also present was the epidemiologist Julian Peto who had correctly predicted the epidemic in the The Lancet in 1995. Peto saw a randomised trial as the only way to address the uncertainty. He even had an acronym ready for the trial - MARS (Mesothelioma and Radical Surgery). Independently of Peto, the English surgeon David Waller and the Irish oncologist Ken O’Byrne had proposed a trial, so we joined forces.

One compelling reason for a trial is that the numbers of cases in years to come will place a heavy burden on resources. If treatments are effective we must fight to have them at our disposal. But what if they are not? The medical philosophers Brody and Miller have laid down the gauntlet with this strong challenge:

“So long as all the physician had to offer the patient was his own time and advice and a few herbs and powders, both medicine and society could comfortably claim that the physician’s duty of fidelity was owed solely to the individual patient. When physicians can, with the stroke of their pens, literally bankrupt the community, the community may no longer be able to tolerate that view of the physician’s duty. (J Med Philos. 1998;23:384-410)

The physician’s perception of where duty lies can lead to some anomalous situations. Respiratory physicians are often the first point of contact with patients, putting them in a powerful position to effectively veto the trial in their area, whether on the grounds of science or ethics. At the other end of the control chain is the surgeon. When presented with information about the trial some surgeons say it is “unethical” to offer this operation, others claim it is “unethical” to deny it to the patients who in their judgement might benefit. Other than quibbling with their casual use of the strong charge that colleagues are “unethical” I cannot argue convincingly against either.

The trial design: A trial which looks like “a lot” versus “a little” is hard for doctors and patients, hence the attempt to balance the arms. In the MARS trial EPP is sandwiched between chemotherapy and radiotherapy as that is how the best survival rates have been achieved. In MARS, the control patients are also given full active trimodality therapy; every treatment is available to the patient - short of EPP.

Is it ethical? The commonest objection we receive is on this basis. Yes, it is ethical. This trial has been extensively discussed in National and International meetings on many occasions during its development phase. It has passed through all the hoops to gain ethical acceptance (MREC) as well as scientific approval (CTAAC and NCRI) and funding (Cancer Research UK). Its ethics have been carefully considered.

Consider the alternative. What can be “ethical” in deliberately choosing to remain in uncertainty and thus consistently use treatments that fail to help - or are actively harmful? It is beyond any individuals clinical judgement to unravel cause and effect. There is a widely variable course in this disease, only the best cases are selected for radical treatment, the treatment has three components, all severe, and not all patients complete all three. Any multivariate analysis is beset with confounding. Whichever way I look at it, I come to the same answer – we need controlled trials. MARS has started as a small scale feasibility study. It is the first proper trial of EPP and it should not be the last.

Posted by Tom Treasure at 07:03 AM | Permalink