Bergamo: The European School of Cardiothoracic Surgery
http://school.eacts.org/

What we know affectionately as the Bergamo School must surely be one of the finest examples of educational beneficence. It was set up by EACTS around 1989 thanks to the imagination and generosity of Lucio Parenzan. The beautiful Villa Elios, in the grounds of the Gavazzeni Clinic, is the home of the school. Bergamo is a historic city about 40km NE of Milan in the North of Italy. The city is itself a delight to visit. The newer part of the city has a fine boulevard on a grand scale lined with stylish shops, restaurants and pavement cafes. A funicular takes you up through the fortified walls of the hilltop ancient city. Around every corner are architecturally breathtaking buildings, villas, churches and no shortage of trattorias and ristorantes. It is to these that the students and faculty retreat to dine together each evening. The students live economically in the seminario. It seems there is less interest then there used to be amongst Italian teenagers to enter the priesthood and there is spare capacity for budget accommodation for those whose vocation is surgery. The semi-monastic environment reminds us of what we have come to Bergamo for – not just to party!

In this wonderful location EACTS runs week long courses, six in all, three levels of thoracic and three levels of cardiac. The faculty are there with the class all day and the days are filled with high quality teaching. Bergamo has its own low cost airport a short bus ride from Villa Elios, it has good train connections and Milan’s major airports are not far away. The next Thoracic Course is 15th to 19th October 2007 usually a nice time to be in Bergamo. http://school.eacts.org/

ESTS School of Thoracic Surgery
http://www.estsschool.org/

A new initiative this year is the School of Thoracic Surgery in Antalya on the Mediterranean coast of Turkey. ESTS have taken a different approach and asked experts in the field to prepare structured lectures within templates provided by the School organisers. As we understand it, the ESTS School faculty of on-site teachers will then deliver these in the class room and lead discussions on them. This will spare busy surgeons the need to travel themselves to Antalya. It remains to be seen how well this will work. Many - maybe most - EACTS thoracic surgeons are also ESTS members. Some will be teaching at Antalya and we have all noted the ESTS approach with great interest. Those who have developed the tradition of Bergamo fear that the loss of direct contact will diminish the impact of teaching. “How could someone else deliver my lecture?” we all ask ourselves. But do we really need to be there ourselves to communicate our own material? Perhaps it is a question of style over content – and content is the more important so that is where the emphasis should rightly lie rather than with the personalities. Time will tell how well this works and we wait for the feedback. It is 14-18 November 2007 and details can be found at http://www.estsschool.org/

EACTS Toolkit Series
http://courses.eacts.org/sections/Thoracic/ThorToolKit/index.html

The Thoracic Committee of EACTS has taken a rather different stance. The Toolkit series is the brain child of Walter Klepetko. The first in what is planned to be an annual event is to be in Prague 1-3 November. Teaching will be very much face to face and as the name suggests it is a course for surgeons in their first couple of years of thoracic surgical training. We have taken the view that at this stage in their careers the students do not need advanced or highly specialised lectures but that the emphasis should be on teaching the basic elements of our craft, and teaching them well – helping the learners to know the toolkit. The aim is that the content should be basic core knowledge and practice. The faculty are chosen primarily for their ability to teach, and we will concentrate on the non controversial and evidence based elements. That is not to say they are not great experts in their fields of interest but it is their ability to communicate that brings them together. The topics for this course are lung cancer staging and pleural disease. The course is free to EACTS trainee members and 50 euros for everyone else. Further information can be found on the EACTS site http://www.eacts.org/ or by go directly to http://courses.eacts.org/sections/Thoracic/ThorToolKit/index.html

I called Sir Bruce (President of SCTS GB&I); it is not that he has negotiated a change in the name of the British and Irish organisation. It was an error somewhere in the editing process. However it is amusing, maybe more to me than to Bruce. Is it perhaps a Freudian slip? The Viennese father of psycho-analysis Sigmund Freud (1856-1939) attributed such errors to the unconscious mind bringing out hidden truths.

Could it be that the Thoracic Committee of EACTS brings Professor Bruce Keogh (also the Secretary General of EACTS) under such pressure that Thoracic Surgery is in the forefront of his mind?

It is good to find a humorous side to events which are somewhat embarrassing to many serious minded European thoracic and cardiac surgeons. The world knows that after five years of highly successful joint EACTS/ESTS meetings the European Society of Thoracic Surgeons will meet separately this year in Leuven, Belgium and the European Association for Cardio-Thoracic Surgery will meet in Geneva, Switzerland. Make what you will of it - but is there something about names that rankles with a group of surgeons who do not operate on the heart?

"What's in a name?” wrote Shakespeare for Romeo and Juliet “That which we call a rose by any other word would smell as sweet."

When the American Association for Thoracic Surgery was formed in 1917 the notion of operating on the heart was regarded as crazy and when that new fangled idea arrived, initially hesitantly in the 1920s but remorselessly in the 1940s, the AATS regarded the heart as just one of the organs within its domain. The Society of Thoracic Surgeons has followed the same convention.

The British organisation was founded as the Society of Thoracic Surgeons of Great Britain and Ireland in 1933 and has changed its name twice I believe. For a while it was thoracic and cardiovascular. I suppose it might change again along the lines inadvertently proposed by Sir Bruce.

I have written before about the commitment of EACTS to surgeons (and thus to the patients in their care) whether their training and practice is combined or exclusively thoracic or cardiac. I echo Shakespeare – what’s in a name?

Nevertheless there is a rhetoric in words and little prepositions can subtly introduce strong messages. Note that some organizations are “of” surgeons and others “for” surgery. Bob Replogle has written about parsing.

I wonder will he put his mind to this one. It’s far too obscure and insubstantial for me to draw anything from it.

The tracheobronchial surgery is technically challenging. It was a major part of the EACTS Advanced Techniques course in Venice 8-10 March 2007. Central to the meeting and arguably the key to its success was a live transmission of tracheo bronchial surgery from Padua.

There are three parts to this blog
• Ethics: I will address some of the issues, pro and con, that surround live surgical demonstrations. That is the ethical and philosophical dimension.
• Mission: The European Association for Cardio-Thoracic Surgery is committed to run high quality thoracic meetings. That is my “Mission Statement” as chair of Thoracic Surgery for EACTS.
• CME: This is a summary of what this meeting was all about. There is one key message – a matter of opinion but seemed to me a conclusion worth taking home.

The sections are labelled so you can select to read or to omit Ethics, the Mission or CME.

Ethics
Is transmission of surgery live to an audience always alright? I do not intend to take a side on this question – it is in any case far too complicated to deal with in a short paragraph as part of a BLOG. I suggest some of the many pros and cons for consideration.

Some points for:
• Surgeons have always watched one another operate. The first meeting of our national Society of Thoracic Surgeons (as it was then) of Great Britain and Ireland met in the Brompton Hospital on 11th November 1933 and the home team Roberts, Tudor Edwards, Price Thomas and Nelson did demonstration operations in the afternoon. And so it has always been.
• Now with the help of video cameras we can keep the operating room clear of "foreign bodies", reduce infection risk and distraction, but really see - from the comfort of a lecture theatre.
• Live surgery addresses the real on-the-spot difficulties encountered in real life. We saw the few moments when the bronchoscope was in the oesophagus (did the operator take longer than some of the audience to realise?). We could see that the laser resection was at times seriously obscured by bleeding. These would have been edited out of a video clip making it all look easy.
• It is in fact so popular that it is the major draw for some meetings and the income of the organisers depends on it.

Some points against:
• The exact contradiction of that last point pro – it is populist, a crowd drawer, and a money raiser say those against. It’s like motor racing or the circus – part of the excitement is that something might go wrong.
• How well informed are the patients that the operators attention will not be 100% on them but at least part on the audience?
• Will the best decisions be made for the patient or will the operator feel compelled to continue the operation as advertised?
• It is inefficient of time. We see a lot of sucking and knot tying which could be usefully edited out so that the critical points can be shown and emphasised.

For a well reasoned critique against read Duke Cameron on the subject
http://www.ctsnet.org/sections/newsandviews/inmyopinion/articles/article-55.html

The Mission
EACTS just like the North American organisations STS and AATS serves the needs of members
• who are purely cardiac surgeons,
• those who do no cardiac surgery,
• and every mix of cardiothoracic practice in between.

In some countries the disciplines are separate but in many training and practice continue as part of the same specialty. EACTS recognises that fact.

Our Association is truly international. This meeting had participants from as far North as Norway, as far South as African, India to the East and Portugal to the West - and from New Zealand. That's as far away as it is possible to be, in whichever direction you set out. There are variations in affluence and expectations of health but surgical principles and humanitarian values are held in common. For most of participants English is not their mother tongue but nor is it for most of the faculty. Our language is International English and again I refer you to Akira Furuse on the subject.

http://www.ctsnet.org/sections/newsandviews/inmyopinion/articles/article-28.html

CME
Three procedures were shown on the live surgery transmission:
• tracheal resection of tracheostomy stricture
• endobronchial laser surgery
• right upper lobe bronchial carcinoid

Lectures on tracheobronchial surgery included:
• tracheal resection for tumours,
• tracheal strictures,
• tracheo-oesophageal fistula,
• bronchial and tracheal sleeve resection,
• postpneumonectomy bronchopleural fistula and the
• bronchial anastasmosis for lung transplantation.

http://courses.eacts.org/sections/Thoracic/AdvTecThor/AdvTecThor-articles/article.html

Over the three days we had outstanding lectures on these topics. Greatly adding to the educational value was the brisk and well-informed discussion. Most of the faculty were present throughout the meeting and this ensured a high level of debate.

As always the meeting depends on the vision, energy and commitment of the local organisers, in this case Federico Rea of Padua and Stefano Elia of Rome, both in Italy.

I am a champion of Evidence Based Medicine (witness our book The Evidence for Cardiothoracic Surgery) and wish we had many more clinical trials on thoracic surgical questions. But I have also recognised how much we rely and will probably always rely on the well reasoned application of our craft skill and experience against a knowledge of anatomy, physiology and pathology. (The evidence on which to base practice: different tools for different times. Eur.J Cardiothorac.Surg 2006)

Tracheobronchial surgery illustrates this well. The first step in thinking about a randomised control trial (RCT) is to formulate in the simplest terms an outline of how the study might be structured.

The acronym PICO summarises this:
P – patient group,
I – intervention under evaluation,
C – control intervention and
O – outcome(s).

In the above list of tracheobronchial problems the individual cases are too few, their presentation too heterogeneous, and the “tricks of the trade” are too many and varied for RCTs to be conceivable for any but a few questions.

From all the excellent teaching imparted, I have a simple but maybe important take home message. Some surgeons stress the importance of techniques of wrapping every bronchial anastamosis to prevent leaks or dehiscence. Others claim never to have seen a sleeve resection leak. Why the difference?

We know how tenuous is the tracheobronchial blood supply. Lung transplantation is the most severe test: the donor bronchus has no bronchial blood supply. An extensive, clean looking dissection in a bloodless field looks good on a video clip but may be inimical to healing. John Dark’s solution is to keep both stumps as short as possible and surrounded by their adjacent tissues. That fits with my understanding of the basic principles and with my own experience.

Forthcoming EACTS thoracic meetings and courses are:
• Bergamo School 15-21 April 2007
• Bergamo School 13-19 May 2007
• EACTS annual meeting (15-18 September 2007) in Geneva with a thoracic TechnoCollege and Postgraduate day on the Saturday and Sunday
• The first in our “Toolkit” series for more junior surgeons (1-3 November 2007) in Prague
• Bergamo School 14-20 October 2007
• Update on Adenocarcinoma - Milan December

The Da Vinci system is delightful to drive. Light touch movements of the surgeon’s fingers translate into accurate and tremor free gyrations of elegant instruments viewed in brilliant light in a three dimensional field. If you like VATS you’ll love this.

Participants are from all over the world including Australia, Hong Kong, India and Iran and several European countries: Austria, England, Holland, Germany, Greece, Italy, Spain, Switzerland and Turkey. EACTS is truly international, providing the biggest gatherings of thoracic and cardiac surgeons world wide.

The language of EACTS is International English. If that needs an explanation it is given by none better than Akira Furuse who as President of The Asian Society for Cardiovascular Surgery reminded us of the distinction to be made between International English and the English native speakers use. His essay on the subject is well worth reading again to remind ourselves of the principles of International English:
http://www.ctsnet.org/sections/newsandviews/inmyopinion/articles/article-28.html

Native speakers instinctively include allegories, sporting analogies, idiom and slang that can be hard to understand if you do not share their culture. I do not understand many American references, particularly to their native sports, even though I speak English. Native English whether American of British may be difficult to understand by the surgeon who speaks English as a second (or third, fourth or fifth) language. I know EACTS members who speak eight, nine or ten languages. That does not mean that I should expect them to understand obscure references to the game of cricket

EACTS embraced International English from the outset. The “founding fathers” came from several different countries and many EACTS members have made their careers in a country far from that of their birth. The geographical spread of surgeons attending in Berne made me grateful yet again that I can speak in my mother tongue but it reminded me that the “dialect” and vocabulary I use should be International English.

EACTS Thoracic will be in Venice next from 8th – 10th March and then at Technocollege and the Annual Meeting in Geneva in September 2007.

Analysis of Canadian data published in the BMJ (2006;332:141-3) revealed that doctors tend to be so influenced by experience that it overrides evidence. Sometimes I read a paper and cannot resist referring to it over and over again in the following weeks and months, so great is its impact on me. This was one such. It tells us that a recent bad experience has a powerful effect on practice, but the extent to which it biases subsequent treatment decisions away from best practice is salutary.

The clinical issues dealt with in this paper include:
- atrial fibrillation (AF)
- stroke as a consequence
- stroke prophylaxis with warfarin
- anticoagulant related bleeds

All headline stuff in cardiovascular medicine.

The BMJ paper caught my attention for a very personal reason. About ten years ago a screenwriter, working on a story involving a medical family, asked for my advice. Her story centred around a high achieving heart surgeon whose wife, a rural general practitioner, was to be portrayed as a more gentle person. The writer wanted a medically authentic incident to make the contrast. We had the lady doctor visit a favourite elderly patient. I suggested that she make the clinical diagnosis of AF and say something like “I know the clever chaps would send you to the anticoagulant clinic but … (sigh) … perhaps we’ll give you some digoxin and settle for that”. The contrast was made, the doctor eschewed intervention in favour of compassion and it worked well in the drama. With hindsight it was not such a good example. AF is responsible for 15% of strokes. Sparing the old man anticoagulation was not the better course of action in his overall interests although, to be fair to myself and to our fictional doctor, the definitive evidence on which practice is based had not then been published.

Whenever we use drugs to reduce the coagulability of the blood, there is a balance between the risk of the thrombus formation we are trying to prevent and the risk of bleeding that we induce with our therapy. Warfarin was first developed as a rat poison and is in part an acronym for the Wisconsin Alumni Research Foundation. It is the commonest oral antocoagulant in use and is also known by its trade name Coumadin.

In the case of lone AF, anticoagulation reduces the number of strokes and despite the risk of bleeding, there is a net benefit (Ann Intern Med 1999;131:492-501). Anticoagulation is not only clinically beneficial but highly cost effective – there is a reduction of need for health care. But doctors fail to anticoagulate a third to two thirds of patients with AF in spite of good evidence for its benefit. You might think that if a doctor had not prescribed anticoagulation for AF and the patient subsequently had a stroke, the doctor would tighten up on practice, but not so.

The authors used a large clinical database – the Canadian Institutes of Health Information (CIHI) records. From this they identified 116,200 patients with lone AF.
- There were 3,921 patients anticoagulated for AF and subsequently admitted with gastrointestinal or intracerebral haemorrhage.
- There were 8,720 patients not anticoagulated for AF and subsequently admitted with a stroke.

They then turned to another database held by the Ontario Health Insurance Plan and from the prescribing information they identified the physician most involved in the care of each patient. Now comes the clever bit. They are no longer interested in these index clinical events but in the physicians’ prescribing habits. It is a bit like the comedy routine for making hot whisky toddy which ends with throwing out the hot water and drinking the whiskey. Our attention is shifted to the physicians and their drug prescriptions for patients under their care in the 90 days before and after the time point determined by the index patient under their care who suffered the serious clinical event of bleeding or stroke. Did they change in treating subsequent patients?

Yes, if their patient had a bleed, but not in line with evidence. The 530 physicians who prescribed anticoagulation for AF were less likely to anticoagulate after a bleed - a reduction from 49% to 42%.

No, if their patient had a stroke. The 704 physicians who had not prescribed warfarin for a patient in AF were not influenced by the fact that their patient had a stroke – before and after warfarin use was similar at 37% and 36% and too low on the basis of the evidence.

You can make mistakes both ways round – errors of commission and errors of omission. In this instance it appears that if the doctors’ treatment resulted in a complication, some changed their practice, contrary to the research evidence, to reduce the chance of that happening again. It is as though the doctor was inappropriately taking the blame, wrongly seeing this as an error of commission. Certainly the INR should have been checked to confirm that anticoagulation was well controlled but a risk of bleeding is included in the calculation for net benefit of anticoagulation in AF.

On the other hand a stroke may be seen as nature taking its course. It did not impinge upon these doctors (based upon the pooled behaviour of 704 of them) as a danger that they could and should have averted. The stroke did not prompt more active management of AF in line with the evidence.

Recall our kindly fictional GP. Some people cannot understand how human beings can be ruled by numbers, while others see no logical way to make decisions without numerical evidence. In this instance, a personal policy founded on the shibboleth “in my clinical experience” is bound to do more harm and less good than following evidence based guidelines. Clinical events such as stroke due to AF and anticoagulant related bleeding are too sparse for us to derive any rule from our own experience, however experienced the individual doctor and indeed, however analytical. The same applies in the prophylaxis of deep vein thrombosis and pulmonary embolism. We cannot compute the competing risks for ourselves. For decision such as these, clinical trials, meta-analysis and databases in the thousands are much more likely to inform best practice than “in my experience”. That is what we should be teaching the next generation of doctors (Student BMJ 2006;14:162-3).

For my contemporaries who chose a life of surgery it must be galling. They used to refer to the less glamorous Public Health physicians as the “drains doctors” but now, with their massive databases and their sophisticated analytical methods, they make the rules. We need to find a balance between “clinical judgement” and the imperative to follow evidence based guidelines and protocols. If they are at odds, it is probably best to follow the rules. As I tell my juniors, there is plenty in their day to day work for which we have no secure evidence. That is where they can and must still exercise judgement.

What is meant by “lung metastasectomy”?
A feature of cancer is that it spreads. In some cases the primary cancer invades blood vessels, fragments break off and are carried in the blood. All the blood passes through the lungs before being recirculated and cancer cells are filtered out. From these seeds new islands of cancer grow. These are called “secondary deposits” or “metastases” - I will use the words interchangeably. The suffix “ectomy” refers to any surgical excision and so we get lung metastas-ectomy.

To narrow the subject to something manageable, I will limit this discussion to colorectal cancer. The two commonest primary sites for cancers are lung and breast but we do not knowingly perform metastasectomy for those; the most typical context for metastasectomy is in colorectal cancer.

The current practice of lung metastasectomy in colorectal cancer
When patients come to us with lung metastases we discuss them in our multidisciplinary team meetings. In advising whether to operate we apply widely accepted selection criteria:
1. fewer metastases
2. longer intervals since the primary cancer resection and
3. less aggressive Duke stage.

I am uncertain about how much good we do by removing secondaries and I believe that a proper randomised trial is needed. My colleagues argue:
· that the evidence is there
· that the patients and their referring doctors want the cancer out and
· a trial would be impossibly difficult.

We have evidence? What is it?
There are no randomised trials. The evidence for a survival benefit depends on observational case series or registries. Survival graphs are presented for different groups, separated by the presence or absence of predictive factors. Patients with favourable factors (listed above: fewer secondaries, longer intervals and less aggressive cancer) live longer.

The flaw in this evidence
Suppose I have a cohort of 100 students and I ask them to form a line, shortest at the front, tallest at the back. I then send the first 25 into class 1 and so on, with the last 25 into class 4. An unsuspecting statistician makes measurements and finds that there are significant differences between the heights of the students in the four classes. Well – no one would be that stupid. Let me make it a little more interesting. I have reason to believe that above average weight and shoe size, and male sex are predictive of greater height. For each of the students I note their weight and shoe size and calculate the mean weight and the median shoe size for the 100. The predictive features I choose are above average weight and shoe size and being male. I send those with three of these features into class 1, with any two features into class 2 and so on until the light and small footed females end up in class 4. I find a suitably blinded statistician and what is she likely to find? The tallest students tend to be in class I. That is absolutely fine but it is not a chance finding – I set it up that way.

Now suppose that I had previously engaged in some legerdemain involving snake oil to make children grow and I claim that my findings are the living proof that it works, and that it works better in heavier males with big feet which is why class 1 is taller than class 4. Replace shoe size, weight, and sex with the number of metastases, time interval and Duke stage, replace snake oil with surgery, and the height with survival and you have the evidence you were looking for. I have not proven that there is no survival benefit but I am unsatisfied with the quality of the evidence offered in its favour. I am not alone. See Torkel Åberg’s writings in the Annals of Thoracic Surgery in 1980 and again in 1997.

But patients want their secondary cancer out!
It sounds better than leaving cancer in there – it stands to reason – or does it? What is patients’ perception of the gain? They must have picked up some ideas from their doctors, so what do doctors think is the gain? The data are presented in terms of survival. The patients’ hopes and expectations are presumably for cure. No indication is given of whether surgery increases or reduces well being.

What do the doctors think?
Surgeons should have a clear idea of what exactly we hope to achieve with every operation we perform.
· In some circumstances it is for a survival advantage; examples are asymptomatic aortic aneurysms, left main stem coronary narrowing, and aortic stenosis. All cause death and in these instances death can be averted by surgery,
· In other instances it is entirely for symptoms; hip replacement and cataract surgery allow the lame to walk and the blind to see.

In cancer we might influence survival or symptoms - either, neither, or both - depending on circumstances. In lung cancer we very rarely operate unless we believe we are able to cure the cancer. On the other hand, in colorectal cancer there are reasons for removing the primary even when cure is impossible. If you have only months or a few years to live it would still be preferable to be spared bowel obstruction, tenesmus, rectal bleeding, sacral pain and fistulae into the vagina and bladder. There is an imperative for colorectal surgeons to operate to control the primary bowel cancer. It does not follow that thoracic surgeons have good reason to take out asymptomatic lung secondaries.

Experts advise it – so it must be right.
My mathematician colleagues, I discovered, believed that because metastasectomy operations are done, there must be a good reason. Let us just burst that belief bubble. In other times doctors as intelligent, as rational and as compassionate as ourselves have done things that we do not do now, including blood letting, cupping, organopexy, colectomy for constipation, industrial scale tonsillectomy in children, ever more radical surgery for breast cancer, and bed rest for everything. These are not now practised. It follows that doctors of the future will not do all the things we do now, but we do not know which interventions they will look back on as unavailing. But you can be sure that there will be some.

Do the expectations of patients and of their doctors match?
Let me challenge another implicit belief: doctors and their patients have a very clear, explicit and shared understanding of what will be achieved by an intervention. Wrong. Modern Western medicine is great at dealing with parts of the problem while missing the patient’s bigger picture. Anne Fadiman’s extraordinary book “The spirit catches you and you fall down” (1997) should be compulsory reading for residents – if only they had time.

I place great emphasis on the patients’ wishes but they must be well informed by doctors, who in turn must be well informed. The surgeon should be able to explain what that individual patient stands to gain or to lose by having the proposed operation. For surgeons to justify removing asymptomatic secondaries for so called “psychological” reasons seems to me to cross a boundary that it would be wiser to recognise and respect.

So what about a trial?
The first response when established practice is challenged is to say that a trial would be impossibly difficult. Difficult always, impossible never. Here is how I would approach it.

· Suppose a patient is sent to a surgeon five years after removal of a very favourable colorectal cancer and has been found to have a single lung metastasis which can easily be removed by minimal access (VATS) surgery. What would we do? Most would take it out even in the absence of sound evidence of a survival benefit.
· Suppose a patient is sent to a surgeon five weeks after an operation for advanced stage colorectal cancer and the chest x-ray shows a dozen metastases. What would we do? A clam shell incision to resect them? Given the absence of sound evidence for a survival benefit, most would not.

So here is the concept. Between these two extreme ends of the lung metastasectomy spectrum there must be patients for whom an oncologist, a surgeon, or a team feels uncertain about whether they are doing more good than harm. If you say “yes” in some cases and “no” to others, there must surely be a zone of uncertainty around the cross over. The trial need only include, indeed can only include, patients where there is uncertainty, that is to say equipoise. How wide the band of uncertainty is and whether it is at the same point for different teams does not matter in the trial design, provided there is unbiased allocation to surgical resection or not. It would be a pragmatic trial – all other treatments would be allowed. The research question is whether the surgery adds any advantage. And let us not forget, there must be some measure of well being apart from just survival. I do not want a futile thoracotomy in the last months of my life just so that some doctor can go home content with the day’s work saying “At least we tried.”

For other conditions treatment effects are not so obvious. Empyema is an example. It is caused by microbial infection and presents at different stages in its progression, with varying degrees of severity, and follows a variable course. Nature does not do a very good job when left to her own devices. Since the time of Hippocrates surgical drainage has been an option but modern management reserves surgery for unresponsive cases because most patients will get better with antibiotics and less invasive drainage procedures. For a summary see the chapter in “The Evidence for Cardiothoracic Surgery” (tfm publishing 2005). What I want to consider here is the belief that the instillation of a fibrinolytic (such as streptokinase or urokinase) has benefit.

The inflammatory response to infection results in deposition of fibrin in the pleural space and the pus becomes loculated and the lung trapped. The rationale is that the if the fibrin can be broken down or “lysed” by fibrinolytic enzymes such as streptokinase or urokinase, drainage should be more complete and the lung should re-inflate more fully and the natural processes will have a much better chance to complete healing. This treatment is complimentary to antibiotics and drainage and is less invasive and thus preferable to surgery. The question is: is it effective?

Five trials designed to study this question reported between 1997 and 2001. They included 24 to 53 patients each, an average of 41, small numbers to address such a question. A Cochrane meta-analysis found them to be underpowered, even when pooled, for the major effects. To resolve the uncertainty, Rob Davies and his group in Oxford, England set up a double blind randomised controlled trial (RCT) which reported on 454 patients, more than twice the number of patients in all the previous trials put together (NEJM 2005;352:865-74). The trial was meticulously carried out with careful attention to blinding and protocol adherence. There was no difference in any outcome, other than a small number harmed by streptokinase. In a trial of this size and breadth any missed treatment effect would have to be very small. Any subset that might have benefited would have to be balanced by one or more other subsets where the effect was in the opposite direction. This Oxford RCT is Level 1++ evidence (http://www.bhiva.org/pdf/pregex4.pdf). I thought that settled the matter but no - eminence struck back.

The BMJ published an editorial addressing the issue (BMJ 21st January 2006;332:133-4). The authors opine that Oxford RCT has major weaknesses while citing, without comment on quality, their own studies which are a fraction of the size. They cite one as showing urokinase and streptokinase as “equally effective” – they (and the BMJ editors) failed to mention that they might be equally ineffective for there were no untreated controls. Even in the title they seek to diminish the worth of the new RCT evidence with the quizzical subtitle “A step forward … ?” The piece has no specified research strategy and is Level 4 evidence at best, but the senior authors are known names in pleural disease, including Richard Light who has contributed so much on pleural disease including giving us Light’s criteria. Hence my phrase “Eminence strikes back”.

Another contradictory publication concerns the drug aprotinin, used to reduce bleeding associated with cardiac surgery. Researchers have been criticised for accumulating too much evidence (The Lancet 2005;366:107-8). There have been 64 RCTs and according to expertly performed meta-analysis, since the 12th the story has not changed: aprotinin reduces bleeding. The new issue that has arisen is about harm associated with its use. It is procoagulant and from its earliest phase II studies there was concern that a thrombotic effect might harm the brain, myocardium or kidneys (Ann.Thorac.Surg. 1993;55:971-6). Ten years later a meta-analysis of 35 placebo controlled trials in 3879 patients (Grade 1++ evidence) reassuringly showed no higher rates of renal failure, myocardial infarction, or death and there was a reduced risk of stroke (JTCVS 2004:128:442-8).

Dennis Mangano, a very well regarded cardiovascular anaesthesiologist has contradicted all of these conclusions (NEJM 26th January 2006;354:353-65). He dismisses the Grade 1++ evidence in a line by saying “nearly all investigations were sponsor-supported and therefore carried unavoidable bias”. If we applied that assumption generally it would leave a big hole in the evidence on heart failure, hypertension, angina, asthma, chemotherapy etc. He draws opposite conclusions based on propensity and multivariable analysis of observational data on 4374 patients divided into those treated with aprotinin, those treated with other antifibrinolytics (aminocaproic acid or tranexamic acid) or who received none of these drugs. The choice to treat patients with aprotinin is a conscious and deliberate medical decision reserved in most practices for the higher, indeed the highest risk patients, while those at lower risk are not treated. This is about as far from random allocation as you can get. We will address the statistical issues in more detail elsewhere but it seems to us likely that the analysis failed to correct for all the differences between these patients. This is Level 2- evidence at best. It seems to fly in the face of all received wisdom about statistical analysis, and to be improbable that mulitivariable analysis of observational data will reveal the truth while meta-analysis of 35 placebo controlled trials is wrong. Nevertheless NEJM published it. It looks to me as though it is another case of eminence trumping evidence.

It is not surprising that these eminent authors seek to defend their positions. They have written papers and books, and are opinion leaders and it must be hard to see their teaching challenged and disproved, but in the world in which I live, evidence for what we do matters. Effective medicine sits alongside ineffective medicine. When the circumstances are complex, we cannot tell which is which without careful sifting of evidence. Cause and effect, benefit and harm, are less obvious in treatment of empyema or managing coagulopathy around heart surgery, than fixing lameness and blindness.

While eminence defends its position, others try to seek improve the chances for evidence. In Paris last week (8th-10th February 2006) I was invited to join thirty others, from North America and Europe, to work on refinements of the CONSORT statement (Consolidated Standards of Reporting Trials - http://www.consort-statement.org/) to make them more applicable to surgical and other non-pharmacological research. The group included leading trial statisticians, clinicians and editors from JAMA, BMJ, Annals of Internal Medicine and The Lancet. Trials in surgery are not easy and many find it difficult to comply with CONSORT requirements (EJCTS 2004;25:299-303) but it is discouraging if the leading journals flout accepted standards of evidence in the debate on important issues such as bleeding after heart surgery and the management of empyema.

It caused me to reflect again (for I have done many times before) on the purpose behind a surgeon in training devoting time to research and publication, and in some instances, earning a further postgraduate qualification for research. Very few go on to become academics and many will never write a paper or do research again. Why do they do it? I can identify four quite separable objectives and to let you understand where this is all heading, I will state now that, in my view, the way they do it in Holland achieves all four - and they do it in style.

1. Appropriate personal development for the tyro surgeon.
2. A real contribution to knew knowledge.
3. A measure of achievement.
4. A rite of passage.

It is believed that a period in original research, as opposed taught courses, develops ability to appropriately modify practice in the light of new knowledge. It equips us for an unknown but inevitably changing future. Some still advocate time in the animal laboratory but in those far off days when it was the norm for every surgical department ot run an animal laboratory, biological knowledge and technical skills overlapped between animal and clinical experimentation. Birim’s work is in lung cancer. There is no animal model for its surgical management. His thesis comprises extensive literature reviews, statistical analysis of risk factors and comorbidity, life table, survival and meta-analysis. These are the vocabulary and skill of modern health care research and he has acquired them. This satisfies my first requirement – it is appropriate personal development.

To make an important contribution to knowledge (my second objective) would indeed be an achievement during a brief spell in a modern basic science laboratory. The individual’s contribution is likely to be a small part of a major project. On the other hand, performing clinical studies and undertaking secondary research (systematic reviewing and meta-analysis) cannot be done without the background knowledge that a clinician brings and it changes practice for the better immediately. Birim’s book adds to the knowledge we use to treat lung cancer. He has added more than he could have done in equivalent time with a young surgeon’s toolkit doing Western blotting in knock-out mice.

It is a competitive world. We have plenty of applicants competing for posts. We need objective ways for individuals to distinguish themselves. In Britain we still produce a thesis of our research work. John Kirklin used to decry the practice, arguing that peer reviewed papers were the proper currency of research endeavour. Birim has his first author peer reviewed papers published in international journals and he has them bound in a book. Two-for-one. How smart is that? My third objective achieved.

Finally, the rite of passage. In Britain we examine a thesis behind closed doors: a drab process which is all too often an anticlimax after much hard work. Defending your thesis in front of your parents, family, friends, compadres, and your surgical chiefs certainly qualifies as a rite of passage. It was great day for Özcan Birim.

A surgeon came, and with him, for the aid
Of sufferers, brought the tackle of his trade,
His forceps, knife and lancet, and a saw
For opening the chest. His smock he wore,
For he that morning from the brink of death
Had pulled one such, and since had scarce drawn breath.

An engineer, whose working days were spent
On figuring and hairsbreadth measurement
And instruments of intricate design,
Having a notion that one might confine
The swelling artery with an armlet strong
But pliant, with the surgeon rode along.

A sufferer, lean-faced and long of limb,
Was in their company, with eyesight dim
For that his eye did flicker to and fro.
His father, a tall narrow man also,
Too soon, in spite of his physician’s art,
Had died with this affliction of the heart.

Joe Treasure adopts Chaucer’s device of a prologue in which he introduces the characters – a surgeon, an engineer and a “sufferer”. The characters in Canterbury Tales met at the Tabard Inn in Southwark. They are on a pilgrimage, a special kind of journey that brings a diverse group of people together in a common purpose. Theirs was to the shrine of Thomas à Becket in Canterbury; the Haj to Mecca is a larger scale contemporary example. As they converge on the place of pilgrimage the tales they tell are informed by the varied experiences of their lives. The story I tell here is of individuals brought together by a single objective: to find a solution better than total root replacement for people whose lives are threatened by aortic dilatation due to Marfan syndrome.

For twenty years I had been working with the problem of surgery for Marfan syndrome. I learned the Bentall operation in its original form; a porous vascular graft was preclotted and joined to a Star Edwards valve during surgery and the composite used to replace the aortic root and valve. My teacher and mentor Donald Ross took me through my first root replacement in 1982 and in 1984 I went, as a pilgrim, to learn from Denton Cooley and the late Stanley Crawford at the shrine of aortic surgery in Houston, Texas. I adopted new methods and welcomed the nonporous grafts and the factory produced composite grafts as they became available. The best I could add personally was to make my surgery as safe as possible and to time replacement to preserve the natural aorta and valve for as long as was safe. I worked with Steve Gallivan, a London University mathematician to time surgery, seeking the nadir of risk - but it was still, for all our calculations, an exercise in brinkmanship. We deferred surgery until the risk of waiting longer was greater than the risk of operating, as best we could estimate either.

Chaucer’s pilgrims met in 1387 close to where Guy’s Hospital stands (we still have a Tabard House within the campus) to set out on their journey to Canterbury. My journey with Tal Golesworthy began at St George’s Hospital, London, at the meeting of the Marfan Association in 2000. As the invited surgeon lecturer, I explained to the assembled “suffers” the rationale behind the annual echo measurement and the timing of root replacement. Tal Golesworthy, a member of the Marfan Association (and also an engineer in design and development) rose to question me. He quickly exposed my complete ignorance of CAD and RP (computer aided design and rapid prototyping, as I was later to learn). The concept is disarmingly simple. The digital output of MRI or CT imaging is used to sculpt, outside the body, an exact replica of the individual’s aorta. On that is made a jacket that fits it to the millimetre. And then John Pepper positions the external support around the aorta: the result as shown on before and after MRI scans are stunning.

The USA surgeon Francis Robicsek proposed wrapping aneurysms years ago. The wraps were fashioned on the operating table from the stiff and non compliant material of cut-up vascular grafts, but what we have now is a perfect engineered external support. We call it an Exostent. It is a much lower risk operation than root replacement, both at the time of surgery and in the long term. No tissue is lost or destroyed. No bridges are burnt in terms of subsequent surgery. Natural blood, endothelial and valve interfaces are preserved. Because it is a low risk pre-emptive operation it can be performed early and the sufferers are spared years of hospital visits for echo measurement, medical brinkmanship and the anticipatory anxiety that goes with it. Can Exostent really be that good? We cannot be sure after five cases and a maximum 18 months follow up but we certainly hope so. It is so much better than anything we could do before.

But to return to my purpose in this blog, it is more to discuss another type of letter, the round robin letter, which families send around at this time of the year. This is a literary device in which, ever more easily thanks to electronic media, we are able to construct and disseminate an annual newsletter of our doings during the year. It typically includes a digest of family news for friends and acquaintances. It is much derided in some quarters and nowhere more amusingly than in Simon Hoggart’s books - I see that after his popular success in 2004 he has a new one for Christmas 2005. Not all agree with Hoggart. Professor Janet Treasure for instance takes a quite different view. She sees these letters as an entirely appropriate medium for the friendly exchange of news. And who can ignore the views of a leading psychiatrist, particularly one who received an NHS Gold Award this year? Those who want an introduction or an update on her recent achievements need only look to Google where she dominates most of the first several pages (I gave up after a dozen) with her writing and clinical work in Eating Disorders. Her team are spread over three sites: the in patient base at London’s famous Bethlem Hospital, the national Institute of Psychiatry on the Maudsley site, and her Professorial department at Guy’s Hospital where she is Chair. This geographically dispersed group tend to gather in our south London home which sits conveniently within the triangle marked by these notable institutions. Along with many international colleagues (to whom warm greetings) they demonstrate no problem with eating and are certainly never disorderly.

These round robin letters are mocked mercilessly by some, as distillations of selected self-congratulatory news that will cast the writer and family in a good light as the darkness of the variously named feasts of the winter solstice arrive. I intend to abide by that tradition in this blog so any spin will be positive. I do realise that readers in the Southern Hemisphere will have long days and ample light but there, it is alleged, the exiting bath water is also spun in the opposite direction. The tradition (and there is a remarkable consistency in the Round Robin form, almost like an IMRaD paper) is to list the children starting with the beloved first born. In our case this would be Sam. He has had ups and downs this year. The downs were the result of falling off his bicycle a couple of times, on the way between Sussex University campus and his home in Brighton. As a result he had broken bits of himself including teeth, small bones, his morale and some of his joie de vivre. He has recovered on all fronts including gaining high marks in his Theoretical Physics course and will be 24 years old next Saturday. Happy birthday Sam. Jean, the no less beloved second born, is in her third year, a pioneer medical student in the new Brighton school. Sussex University had a strong Psychology Department now reflected in its new Medical School (also in its third year, hence Jean the pioneer) for she is now in the unnerving position of having professors and teachers very familiar with her mother’s work. To date, connections with cardiothoracic surgery have passed relatively unremarked.

I stray from my subject. It is no chance that the titles of Hoggart’s books with their hilarious exposés of the most naff and self congratulatory of Christmas letters are entitled “The Cat Who Could Open The Fridge” and the “The Hamster That Loved Puccini” because after the parents’ career moves and the children’s achievements are told, anecdotes about the family pets follow. We could not compete there. Our London menagerie is down to the last few quail, canaries and cockatiels. As Jean moved away to Medical School and the bravado of inner London’s foxes escalated, our garden was no longer the haven it was for geese, ducks and bantam fowl. Tilly, the last surviving goose, died peacefully earlier this year, in the country at grandma’s. But with the spring, we hope to return to animal husbandry. The ten acres of Falcon Farm have been reshaped over the eight years with restored and new planted hedgerows, an orchard, a nut grove, woodland and ponds. The place has come alive with the creatures previously driven out by decades of modern farming. Our man made ponds have blended into nature and shy moorhens have nested and brought up their families these last two years. We have introduced toads and newts, probably unnecessarily because slow worms and an abundance of frogs have made their own way. Our agricultural efforts have been in the orchard and kitchen garden but so far I have not mentioned the meadow. The five acres where we have sown old fashioned grasses and wild flowers, now sheltered by woods and hedgerows, has caught the eye of a gentle, earth friendly local farmer who asks if it can be home to some in-calf Sussex heifers. What have I been waiting for? What I have needed though is the carer as well as the cows.

The European Association for Cardio-thoracic surgery (EACTS) has occupied a great deal of time this year and much travelling, almost on a par with Janet’s, and not compatible with tending cows and calves. In 2004 the travels included Turkey, Greece, Spain, France, Italy, Belgium, Holland, Florida and California and in 2005, which will be dominated by my Presidential year, so far scheduled are Ireland, Philadelphia, Chicago, Romania, Poland and Sweden. I have already referred to the devastation of Europe’s medical and scientific collaboration as a result of terrible wars of the twentieth century. We seem to have stopped counting after two. EACTS and ESTS are part of the rebuilding of medical Europe. The first wave was in Western Europe but now the Eastern European countries are a playing a large part and our annual meetings of Thoracic and Cardiac surgeons are the largest in the world. But over Christmas, I will relish a quieter time. We hope it will be family time, and on Falcon Farm.

Sam and Jean share a home in Brighton, the place to be, the place to party - but a curious deadness falls on England over Christmas. Not just England. The legacy of the war left Europe divided and caught between the influences of the USA and USSR. John le Carre in Absolute Friends describes the anarchists and wannabe urban terrorists of cold war Berlin who on Christmas Eve “experience one of those moments of self-revelation from which there can be no retreat. Already by the twenty-third of December the squat is three-quarters empty as communards abandon principle and slink home to celebrate in the bosom of their reactionary families. Those who have nowhere to go remain behind like uncollected children in a boarding school.” I hope I will never be seen as reactionary or that Sam and Jean will ever need to slink.

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.

Fifty years ago this month, in November 1955, the thoracic surgeon Geoffrey Flavell performed a remarkable clinical experiment. He asked a patient with lung cancer if he would consent to a thoractomy during which Flavell would only divide the vagus; he proposed re-opening the chest incision a week later to perform the lobectomy (Lancet 1956; 270:260-262 ). In May this year I gave the inaugural Geoffrey Flavell Lecture at the Society of Apothecaries in London and that prompted me get out the original Lancet paper. The man had severe hypertrophic osteoarthropathy (HPOA) Flavell wanted to test the hypothesis that the vagus nerve was the afferent pathway of a mechanism that caused clubbing and the more severe changes of HPOA. The man had first developed painful swelling of the ankles in August and over the next couple of months the knees, then the wrists, elbows and fingers also became stiff and painful. “Radiography showed typical hypertrophic osteoarthropathy of all the long bones”. Remember that this was about 20 years before the first CT images and Flavell relied for assessment of operability on simple radiology and his rigid bronchoscope. There was a small opacity in the upper lobe of the left lung which was diagnosed as lung cancer on sputum cytology. “The patient agreed to a two-stage operation”.



Dr. Geoffrey Flavell

At the first operation on 23rd November 1955 Flavell disturbed nothing but the vagus nerve and divided it just distal to the recurrent laryngeal nerve. The following morning the patient was asked if he felt any different. “Goodness me, yes” Flavell quotes “all my pains are gone; and look – I can bend my knees for the first time in weeks!”. The swelling went in 48 hours and the pain never recurred. A week later Flavell removed what proved to be a squamous carcinoma without lymph node metastases.

The background as Flavell wrote was this: “It has long been known that resection of the growth is followed instantly by cessation of all pain …” This is accepted whenever I have discussed it with colleagues; it is a striking and consistent observation. Flavell made the further observation that pain is also relieved in patients in whom resection had failed, but a preparatory dissection around the hilum had been performed. He describes two such cases in this paper. In another two cases, both on the right, he divided the vagus above the azygos vein, the last through a minimal thoracotomy. In all cases, the patients’ pain was completely abolished. In his conclusion Flavell proposed division of the vagus nerve in inoperable cases with the objective of relieving pain.

As a resident at the London Chest Hospital in 1978, I was studying the teaching collection of x-rays in the radiology department. I chanced upon the films an inoperable right sided lung cancer and a pathology laboratory report of a confirmatory biopsy of the vagus nerve obtained through a mediastinoscope. It was impressed upon my memory. Reaching and dividing the vagus – and sending a bit to the lab – seemed to me not something that would have been attempted by the faint hearted or unskilled. The surgeon was a resident called Magdy Yacoub. It was this chance discovery of the story that prompted my interest in HPOA and my curiosity remains. The young Yacoub reported this and another case (Br J Dis Chest 1965; 59:28-31, Br J Dis Chest 1966; 60:144-147). One was a man who was admitted to hospital in 1962 with left sided cancer which had already destroyed the recurrent laryngeal nerve. The pain from HPOA was so severe that he could not sleep. Division of the vagus in the neck gave dramatic relief. In the second case in 1964 the patient had lost the use of his hands due to the severity of HPOA. This was the man in whom Magdy passed a mediastinoscope through the usual neck incision divided the vagus nerve in the tracheo-oesophageal groove. “The joint and bone pains subsided immediately, and five days later he could close his fists easily”.

Flavell and Yacoub reviewed the evidence for proposed mechanisms. On the basis of these cases and their review of the experimental and clinical evidence they believed that the ipsilateral vagus nerve was the key afferent pathway. While the observation that pain is consistently relieved by resection is generally agreed, standard clinical texts on lung cancer shy away from this vagal hypothesis, stating that the mechanism is unknown. The possibility of a vagal mechanism is mentioned in some texts but usually no source is cited. Little credence is given to the vagal contribution and various humoral mechanisms are postulated. Since 2000 there are fewer than 100 references to HPOA in PubMed, predominately case reports of rare associations and strange phenomena. Lung tumours cause a wide range of paraneoplastic syndromes due to the release of proven or postulated substances and a neural and humoral mechanisms could co-exist. However, the vagal mechanism is not favoured. It appears to be largely discounted. Why?

Is there a question about the reliability of these surgical reports? This seems to me unlikely. Cardiothoracic surgery was then and remains a very public specialty. The London Hospital and the London Chest Hospital were both major contributors to teaching, training and clinical reports in the 1950s and 1960s. Flavell named each referring physician in his Lancet paper. Yacoub acknowledged his senior colleague Jack Belcher when he wrote in the British Journal of Diseases of the Chest (a journal which one of my mentors in the 1970s used to refer to as the Brompton Hospital “school mag”). Erroneous or over enthusiastic assertions could hardly have gone unremarked.

There is the possibility that the dramatic relief reported by Flavell and Yacoub was a placebo effect - a result of suggestion. There are good reasons to consider that possibility. When we see lung cancer patients with HPOA at least one doctor, and probably several, will tell them “That pain will go away when we take the cancer out”. A thoracotomy would surely qualify as an intervention sufficient to prompt a placebo effect. And yet the effect is consistently reproducible and the physical and radiological changes regress, along with the pain. A placebo effect seems unlikely.

HPOA is generally regarded as at the severe end of the clinical spectrum of the physical changes that are seen under the general heading of finger clubbing. Clubbing is said to have been described by Hippocrates in his account of empyema and is seen in about a third of cases of lung cancer. The incidence of HPOA in lung cancer was about 3% (9 out of 280) in a consecutive series seen between about 1970 and 1975. The occurrence of “Hypertrophic pulmonary osteoarthropathy without clubbing of the digits” (Skeletal Radiol 2001; 30:652-655) is so rare as to be published only in as few as four case reports.

In many discussions of the subject which I have had with very well informed physicians, Flavell’s evidence is played down and it is because the mechanism seems to them to be implausible. The preferred theory is that there is some form of tumour derived growth factor which is responsible. Although the surgical “experiments” of Flavell and the clinical application by Yacoub provide strong empirical evidence for a central role for the vagus, the theory is not liked because it does not fit with any known physiological mechanism or that appears plausible in the light of current accepted scientific knowledge. There is a danger there. In the 1840s Semmelweiss provided evidence that hand washing with chlorinated water between the post mortem room and the labour ward dramatically reduced the death rate from puerperal sepsis but his contemporaries were able to discredit him because the microbes had “never yet been seen”. I would accept that any parallel between the discrediting of Semmelweis and the forgetting of Flavell would be far too strong but the more gentle message from Belloc is worth recalling: “Oh! Let us never never doubt what nobody is sure about”.

If anyone has more evidence about HPOA and the vagus I would be interested to know. With modern minimal access approaches, perhaps we should consider offering this form of palliation in inoperable lung cancer.

THE MICROBE
by: Hilaire Belloc (1870-1953)
HE MICROBE is so very small
You cannot make him out at all,
But many sanguine people hope
To see him through a microscope.
His jointed tongue that lies beneath
A hundred curious rows of teeth;
His seven tufted tails with lots
Of lovely pink and purple spots,
On each of which a pattern stands,
Composed of forty separate bands;
His eyebrows of a tender green;
All these have never yet been seen--
But Scientists, who ought to know,
Assure us that is must be so...
Oh! let us never, never doubt
What nobody is sure about!

"The Microbe" is reprinted from More Beasts for Worse Children. Hilaire Belloc. Duckworth, 1912.

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.