The Processes and Challenges of the WHO Blue Books
October 26, 2021Information
October 21, 2021
Yale Pathology Grand Rounds
Ian Alexander Cree, BMSc (Hons), MB, ChB, PhD, FRCPath, ALS
ID7075
To CiteDCA Citation Guide
- 00:04Get started then.
- 00:40Hi everyone, welcome to today's grand round.
- 00:44Our speaker today is Dr. Ian Cray.
- 00:50Ian is a pathologist and an
- 00:54international civil servant.
- 00:56Is based at the International Agency
- 00:59for Research on Cancer in Lyon,
- 01:03where Ian is the head of humor
- 01:07classification responsible for all
- 01:09the blue books that we keep buying.
- 01:13And he is also head of evidence,
- 01:15synthesis and classification.
- 01:20He ended his undergraduate education at the
- 01:25University of Dundee and then his MBCHB,
- 01:30followed by a PhD in Immunology
- 01:33at the same place, and even then
- 01:38finished his pathology training.
- 01:40He was trained as a general
- 01:43pathologist at the same place,
- 01:45becoming a consultant
- 01:47pathologist in his alma mater.
- 01:51But since then,
- 01:52Ian has moved several times his
- 01:55previous positions held were senior
- 01:58lecturer and at the Institute of
- 02:03Ophthalmology and Ian mentioned that
- 02:06his major work was in ophthalmologic
- 02:09pathology and he got so excited
- 02:12with it that he was instrumentally
- 02:15involved with the first blue book
- 02:19on my pathology and his working.
- 02:22To bring out the second edition,
- 02:26or rather the 5th edition,
- 02:27what would be equivalent to the 5th edition?
- 02:31He went on to become consultant
- 02:34pathologist and a professor of
- 02:37histopathology at Queen Alexandra
- 02:39Hospital in Portsmouth and then
- 02:42Southampton in England and then
- 02:44became a professor of pathology at
- 02:47University of Warwick and a consultant
- 02:51pathologist at University Hospitals.
- 02:54In Coventry and Warwickshire,
- 02:56and just when he was getting ready
- 02:59to retire as the British system.
- 03:02And courageous their sin apologist to retire.
- 03:06He got an offer from Dublin to help
- 03:09them publish the new series of Blue
- 03:13books and become an international civil
- 03:17servant and of course moved to France.
- 03:22So just to give an idea that
- 03:25the series Blue Book,
- 03:27this is what they look like for those of
- 03:30us who are not in diagnostic pathology,
- 03:34and Ian has been involved with the 4th
- 03:37edition of the skin tumor Blue Book,
- 03:40the eye tumors and he is on the
- 03:44editorial board of the 5th editions
- 03:47of tumors of the digestive system.
- 03:50Breast humors soft tissue.
- 03:52In bone,
- 03:53female genital tract tumors
- 03:56and thoracic tumors,
- 03:58Ian's career has been built on
- 04:01translational path ologist,
- 04:03and on translational pathology,
- 04:05and he was involved in developing a
- 04:09number of molecular diagnostic methods,
- 04:13and he let you kiss early
- 04:16Cancer detection consortium.
- 04:18He has published more than 270.
- 04:22Papers and more than 150 of them
- 04:26were as first and last authors,
- 04:29and has been a coauthor in
- 04:32more than in about 8 books.
- 04:35So with that proof.
- 04:38Brief introduction.
- 04:40They will let Ian take the floor.
- 04:43Thank
- 04:44you very much. I'll start by saying
- 04:46thank you to to you for inviting me.
- 04:48It's a great pleasure to be here,
- 04:50at least virtually.
- 04:51I'm sorry I can't see the autumn
- 04:54colors around you and get to see
- 04:56and meet some of you properly,
- 04:58but maybe in the future. Who knows.
- 05:00I'm going to start by sharing my
- 05:02screen if I may, because I think
- 05:04that's the first order of business.
- 05:06Uhm, hopefully you can all see that.
- 05:09Uh, the.
- 05:12So this is the point where you have to
- 05:15shout if you can't because once I put
- 05:18the presentation on I can't see you.
- 05:20So I think
- 05:22we can see it
- 05:23good. Alright, let's go so.
- 05:27I was asked to talk about the.
- 05:30Processes and challenges.
- 05:31And this is not yet coming.
- 05:33Sorry though,
- 05:34it is of The Who blue books and.
- 05:40It's it's certainly had its challenges,
- 05:42and one of the challenges
- 05:44has been the process,
- 05:45so I think it's a fairly good title,
- 05:47actually. First of all,
- 05:48the declaration of interests.
- 05:50I am a pathologist has been said
- 05:51and based at the International
- 05:53Agency for Research on Cancer,
- 05:55which is a part of the
- 05:57World Health Organization.
- 05:58But the opinions I'm expressing
- 06:00our of course personal.
- 06:02I'm going to start with this.
- 06:03This is one of my favorite slides.
- 06:05Now I have to say it's a picture of Carl,
- 06:08Aeneas and Linnaeus described the
- 06:11natural world around us and we still
- 06:14use the classification that he put
- 06:16together and published in 1758.
- 06:19And if any of the blue books are still
- 06:21knocking around in 300 years time,
- 06:23I should be extremely pleased.
- 06:25But I'm afraid I won't be here to see it.
- 06:28The natural progression,
- 06:30though of all taxonomies,
- 06:32is that they evolved.
- 06:34And the natural our taxonomy of the
- 06:38natural world is also still evolving.
- 06:41This was a story from last Christmas.
- 06:44Nice Christmas story.
- 06:46Gentoo Penguins,
- 06:47which all look rather similar.
- 06:49There were actually two species,
- 06:52but now there are four,
- 06:53and that's on the basis of genetics.
- 06:55And that's exactly the same thing
- 06:56that's happening to a lot of tumors.
- 06:58Of course,
- 06:59where genetic investigation
- 07:01is proving very helpful.
- 07:03So taxonomy is the science of
- 07:05defining and naming groups of
- 07:08biological organisms on the
- 07:10basis of shared characteristics.
- 07:11And cancer classification is also based
- 07:15on the shared characteristics of cancers.
- 07:17That's currently mainly
- 07:19Histology and genetics,
- 07:20but it also includes things like radiology,
- 07:23cytology and a host of others.
- 07:27We take our remit for doing this
- 07:29from the 10th World Health Assembly,
- 07:32which in 1957 resolved to continue
- 07:35work on formulating international
- 07:37definitions of normal stature
- 07:39and statistical classification.
- 07:41The World Health Assembly is the governing
- 07:44body of the World Health Organization.
- 07:46It comprises 194 countries at the moment.
- 07:52I should say that I arc is a
- 07:55specialized agency of the World Health
- 07:57Organization and therefore it doesn't
- 07:59have the whole 194 to deal with.
- 08:02We've only got 28 and I think some of
- 08:04us feel that it's probably quite enough,
- 08:06but we would always like more.
- 08:09In the 4th edition, the WTO Bluebooks,
- 08:12which started in the 1960s, UM,
- 08:15became a synthesis of scientific evidence of
- 08:19illustrative cases and diagnostic criteria.
- 08:23They became indispensable to many
- 08:27pathologists because they gave you
- 08:30the international standards that
- 08:32were required to diagnose tumors.
- 08:35And I think that's where we owe
- 08:38them a great debt of gratitude.
- 08:40However, it must be said that
- 08:42not everybody was pleased.
- 08:44And those of you that have seen this slide
- 08:46before, and it has been around a bit.
- 08:48I got mine from that at Jabot and I'm very
- 08:51pleased to give her the credit for that.
- 08:55But here you can see a dinosaur.
- 08:57It's obviously a gynecological dinosaur,
- 08:59and it's eating a CNS blue book.
- 09:02I'm not sure they're actually suggesting
- 09:04that that guy, any pathologist,
- 09:05start reporting all the CNS pathologies.
- 09:07So don't worry too much.
- 09:09But certainly there were suggesting that
- 09:11these books were somewhat out of date.
- 09:14By the time they were published and they
- 09:16took about three years to publish each book.
- 09:19So that was one of the challenges the entire
- 09:224th edition took over 12 years to publish,
- 09:25so it was a mammoth task,
- 09:27and one that a smartly small
- 09:29number of people took on and did,
- 09:31and we owe them a great debt of gratitude,
- 09:34of course.
- 09:36However, we needed to innovate.
- 09:38We needed to change things,
- 09:39so there are a number of
- 09:41innovations for the 5th edition.
- 09:43And these really fall into three categories.
- 09:46The first was better governance.
- 09:48The entire 4th edition was actually
- 09:50led by just three pathologists,
- 09:53and that's probably nothing like enough.
- 09:57I certainly when I was appointed,
- 09:59didn't wish to try and lead it myself,
- 10:02and therefore I decided it would be a
- 10:04good idea to have an editorial board.
- 10:06And I borrowed from the National Institute
- 10:09for Clinical Excellence in the UK,
- 10:11which in its committees has both standing
- 10:14and expert members and the standing
- 10:16members are there to provide the
- 10:18continuity and the overall expertise,
- 10:20and they're usually
- 10:21fairly senior individuals.
- 10:22The experts are there to provide
- 10:25the hard experts opinion that's
- 10:28required to make decisions within
- 10:31health technology assessment.
- 10:33In the case of Nice or classification
- 10:36in this instance.
- 10:37And we try to do what we
- 10:39do based on evidence,
- 10:41and that now includes things
- 10:43like systematic reviews,
- 10:44which historically pathologists have
- 10:45not really been involved in very much.
- 10:49We are about evidence and not eminence.
- 10:53Expert opinion is still is still
- 10:57very relevant, but it's not.
- 11:00It's not of great significance.
- 11:03It's really important that we.
- 11:06Have also selection by informed
- 11:09Bibliometrics and we we we.
- 11:14We use both author and editor
- 11:17selection using this process,
- 11:19which allows us to look at what people
- 11:22have published and decide what is.
- 11:25What is is is most fair in
- 11:27in terms of who to appoint.
- 11:30It's not a simple process,
- 11:32it's something we have to do quite carefully,
- 11:34because clearly we don't want everybody
- 11:36to come from one country or another.
- 11:38We want to have a geographical spread as
- 11:40well as a spread of expertise and experience,
- 11:43and we try and do that using a system
- 11:45which we've actually developed called
- 11:47the Blue Book Expert Selection Tool,
- 11:50which is a form of cross.
- 11:54It uses cross referencing to identify
- 11:57papers published by authors and
- 12:00who they have Co published with,
- 12:02so it's a Co citation system.
- 12:05I'm not going to talk about that much more,
- 12:07actually,
- 12:07'cause it's it's quite complex.
- 12:10In terms of quality.
- 12:13Uhm?
- 12:14We've got a hierarchical classification
- 12:16using Linnane principles,
- 12:18and that gives us some tremendous scope
- 12:22to collapse and expand particular
- 12:26diagnostic categories quite easily.
- 12:29In terms of quality,
- 12:30I'll talk about that a little bit more later,
- 12:32and we've certainly upped the quality
- 12:34of images we tried to ensure that
- 12:37references are up to date and relevant,
- 12:40and there's quite a bit more.
- 12:43We get our epidemiology from epidemiologists,
- 12:46which is a bit of a novel turn,
- 12:48but the epidemiologists in arc and
- 12:50there are a lot of them were fairly
- 12:53scathing about the pathologist's
- 12:54ability to do this, so we said,
- 12:56well, why don't you do it?
- 12:58And luckily, they said yes.
- 13:00We try to incorporate new
- 13:02information whenever we can,
- 13:04and we harmonize topics across series,
- 13:06particularly neuroendocrine neoplasms,
- 13:09humita,
- 13:09lymphoid disease and soft tissue tumors.
- 13:16We've improved the speed with which
- 13:18we can produce the books by just
- 13:21taking a process management approach.
- 13:23It's lean management, really.
- 13:26So we've tried to improve things
- 13:29at every stage by setting deadlines
- 13:31and trying to meet them and also by
- 13:35improving the way in which we handle
- 13:38matters in an automated fashion as far
- 13:41as possible within the software that
- 13:44we used to produce the whole thing.
- 13:46We have a website that allows easier
- 13:49access to references to whole slide
- 13:51images and it now allows notes and
- 13:53it also allows feedback so that
- 13:56then allows those that are part
- 13:58of the community that use and buy
- 14:00the books and the website too.
- 14:05Come back to us in a much easier way
- 14:07and a much more organized way too,
- 14:09which is probably better.
- 14:11So the 5th edition books look
- 14:13a little bit different.
- 14:13The 4th edition,
- 14:15they've got a slightly modernized cover.
- 14:17There are slightly lighter blue,
- 14:18so you can tell which is which on the shelf,
- 14:21and there's quite a lot of thought
- 14:23gone into the design of both
- 14:24the cover and the spine.
- 14:26We've kept the nine photographs in the
- 14:28front 'cause that makes them instantly
- 14:30recognizable as a WHO blue book.
- 14:33And we've gone for a two column
- 14:35format inside.
- 14:36So the photographs,
- 14:37which were rather small in the previous
- 14:40edition in a three column format
- 14:41and now on the whole much larger,
- 14:44and that certainly helped.
- 14:46We've incorporated clinical photographs.
- 14:48We've incorporated epidemiological
- 14:50graphs as well. Uh, diagrams.
- 14:53So there's a wealth of information in these.
- 14:56Volumes,
- 14:57but I should say at the outset
- 14:59they are not textbooks.
- 15:01This is a taxonomy would be describing
- 15:04the criteria for each tumor type,
- 15:06which results in that classification.
- 15:08We're not trying to tell you
- 15:10how to diagnose them,
- 15:11that's something that a textbook would do.
- 15:14In terms of who?
- 15:16Therefore,
- 15:17the other thing is that they're
- 15:19not just for pathologists,
- 15:20this is the taxonomy of cancer,
- 15:22and just as a gardener or a.
- 15:27A farmer will be interested
- 15:29in the plants on their land.
- 15:31People with different ideas of of
- 15:33what they want are quite capable
- 15:36of looking at the same taxonomy
- 15:38and getting something from it.
- 15:40The doublet show blue books then
- 15:42provide a definitive evidence based
- 15:44classification of all cancer types to
- 15:46enable diagnosis and research worldwide.
- 15:51And our diagnosis of cancers
- 15:54and other tumors underpin
- 15:56individual patient treatments.
- 15:58Of course, that's why we do it,
- 16:00but they also underpin research
- 16:02into all aspects of cancer,
- 16:04causation, prevention and therapy.
- 16:06And then they also underpin education.
- 16:09So it really is the basis of
- 16:10an awful lot of what we do.
- 16:14In terms of the classification turns,
- 16:16we use usually A5 level
- 16:20classification with subtypes.
- 16:22As a further level.
- 16:24So we start off, usually with sites,
- 16:27for instance stomach.
- 16:29We then have a category which is
- 16:32often lineages based epithelial plasm,
- 16:34something like that and then a
- 16:37family or class which in this
- 16:39example I've given as abnormal other
- 16:42pre malignant neoplastic lesions.
- 16:44We might separate those and some other
- 16:46volumes and then a type would be adenoma.
- 16:49So you'd expect to see gastric
- 16:52adenoma in the diagnosis perhaps.
- 16:55And then the subtype, UM,
- 16:58would be public land in this example.
- 17:01Variant is not a word.
- 17:03We try to use anymore within the blue books.
- 17:07In terms of the Histology or
- 17:09what is now called the subtype.
- 17:12The reason for that is partly because
- 17:14it's been somewhat hijacked by others.
- 17:16It's used variably by geneticists and
- 17:19by others to describe variations that
- 17:21may or may not be part of the classification.
- 17:24So we've tried to avoid it where possible
- 17:28and deal with it when we absolutely have to.
- 17:32We haven't, though I should say,
- 17:34switched from calling mutations as you
- 17:36may very well know them sequence variants,
- 17:40which is what most geneticists would do now.
- 17:43In terms of staging grade,
- 17:45those are dealt with separately
- 17:48within the books.
- 17:49Honestly, the early sort of
- 17:51points that we realized was that.
- 17:53Your view of the classification really
- 17:55depended on what you were doing.
- 17:58So if you were a geneticist or a histo,
- 18:00pathologist or radiologist,
- 18:04you looked at things very differently.
- 18:06And that's a multidimensional problem
- 18:09and it's very hard to put multiple
- 18:11dimensions into a two dimensional book.
- 18:14So we decided to make it slightly easier
- 18:17on ourselves by having a database.
- 18:19So the classification is now a database.
- 18:22It's a relational database and it means
- 18:24that we can now use the headings for
- 18:28each of the tables to develop the two
- 18:31dimensional layout you see in the books,
- 18:34and that's why you will see
- 18:37things like etiology unknown.
- 18:40It's not because we didn't.
- 18:43Yeah,
- 18:44we didn't leave etiology Alex because
- 18:46there was nothing to put in there.
- 18:48We actually have to say something for
- 18:51each of these headings in the book.
- 18:53We don't, uh.
- 18:57Make any distinction underneath these
- 18:59headings so that the open bullet points are.
- 19:03You can be used or not used as as
- 19:05people wish and you'll see them
- 19:07in some of the larger sections,
- 19:09particularly where it breaks up the text,
- 19:11but you won't otherwise see them at all.
- 19:16So we start off with the definition.
- 19:17The definition now has to be less than
- 19:20100 words and it has to define what
- 19:23something is and not what it's not.
- 19:25And it has to be usable by
- 19:28people outside pathology.
- 19:30Uhm, because it is used on its own,
- 19:32it's used for instance,
- 19:34with the ICD 11 codes.
- 19:36I won't go into coding 'cause
- 19:37that is pretty specialist,
- 19:39but suffice it to say that
- 19:41that we have the International
- 19:43Classification of Diseases on koleji.
- 19:46Uhm, which is used largely
- 19:48by cancer registries,
- 19:49and we have the International
- 19:51Classification of Diseases Version 11,
- 19:53which is the new one that's taking
- 19:56over from ICD 10 at the moment.
- 19:58And it's still really under development.
- 20:02We give related terminology and
- 20:04we divide that into two types,
- 20:07acceptable and not recommended.
- 20:09And that's because we don't want
- 20:12to stop people doing things.
- 20:14It's not our role,
- 20:15but it's certainly necessary to
- 20:17say what is a good idea and what
- 20:20perhaps isn't such a good idea.
- 20:22We list subtypes and we described
- 20:24them under whichever category they
- 20:26all categorization they come into.
- 20:29So if it's a histological
- 20:30subtype comes under Histology.
- 20:31If not,
- 20:32it might be a genetic one described
- 20:34under the molecular pathology.
- 20:38The clinical features and radiology come
- 20:40next and we put them together because
- 20:42they seem to fit fairly well that way,
- 20:44at least in in the first book we did,
- 20:47which was in digester.
- 20:49Uhm, epidemiology.
- 20:50I've talked about already and etiology.
- 20:53We covered the causes and this
- 20:56predisposing factors going here so
- 20:58that the predispositions genetic
- 21:00predisposition would go in there.
- 21:03In terms of pathogenesis,
- 21:05that is largely these days molecular,
- 21:08but we do try to make sure that we cover
- 21:11other other parts of that as well.
- 21:13A macroscopic appearance in
- 21:15histopathology probably needs no
- 21:17introduction to this audience,
- 21:19but it has all the usual things
- 21:21you'd expect under there.
- 21:22We try to have differential
- 21:24diagnosis at the end,
- 21:25which is very helpful to to
- 21:28many pathologists I know.
- 21:30In terms of cytology,
- 21:32that is now being dealt with,
- 21:34in addition to the blue books as
- 21:36a series of reporting systems,
- 21:38foresighted pathologists and we've
- 21:40teamed up with the International
- 21:42Academy of Cytology to produce those,
- 21:44and I'll show you a mock up of the
- 21:47cover later in terms of diagnostic
- 21:50molecular pathology that is restricted
- 21:52to what you would do in a patient.
- 21:54So if you wouldn't do another patient,
- 21:56it won't appear there.
- 21:57It'll appear on the pathogenesis.
- 21:59One of the innovations that we have
- 22:03introduced is the addition of essential
- 22:06and desirable diagnostic criteria.
- 22:09And the reason we've done that is
- 22:12because in the previous 4th edition
- 22:14it was sometimes quite hard to
- 22:16find out which were the essential
- 22:19features that you needed to see in
- 22:21order to make a diagnosis or to
- 22:23classify tumor within a certain range.
- 22:26And that's something that we felt was.
- 22:29It was a good idea to actually write down,
- 22:31so that's what we've tried to do.
- 22:32It's quite a challenging experience,
- 22:34and some of you I know in this
- 22:36room have had it.
- 22:38We use the UICC staging system
- 22:41because we are international.
- 22:42This is the international staging system.
- 22:45But UICC and AJ CC work
- 22:47very closely together,
- 22:49so if you're using the AJC,
- 22:51it's the same thing.
- 22:53In terms of prognosis and prediction.
- 22:57We talk about prognostic factors
- 22:59and predictive biomarkers in some
- 23:01detail in certain tumor types,
- 23:03where that's really important,
- 23:04and that's an increasing number.
- 23:05Of course,
- 23:06and then we're developing links
- 23:08to other resources which will
- 23:10mainly go on the website,
- 23:11and that's particularly to the international
- 23:14collaboration for cancer reporting.
- 23:16CAP is one of the founding
- 23:18members of that organization,
- 23:20as is the Royal College of
- 23:22Pathologists and many others,
- 23:25and.
- 23:26It produces the structured reports which
- 23:29depend very heavily on the blue books
- 23:33and the staging resource is produced by UIC.
- 23:37In terms of numbers,
- 23:38we have roughly 200 people
- 23:40on the editorial board,
- 23:43between the standing and the expert members,
- 23:45or will have by the end of the series.
- 23:48The authors are really need to
- 23:50update that figure because we've
- 23:51already hit two and a half thousand.
- 23:53Uhm, so it's a it's a very big project,
- 23:57this one and it has a lot of
- 23:59people involved in it and we're
- 24:00extremely grateful to all of them.
- 24:02It's a it's a mammoth task and it has
- 24:06enormous impact for patients particularly.
- 24:10In terms of subscribers,
- 24:13we think we have about 60,000.
- 24:15They are mainly pathologists,
- 24:17but not entirely probably
- 24:19around 8590% pathologists.
- 24:22And if you're anything like me
- 24:24when you reach for your blue book,
- 24:25it's not there because somebody borrowed it.
- 24:28And therefore we think we've got a lot more
- 24:31users than we have actual subscribers.
- 24:33Uh, the whole team is the whole thing,
- 24:37is run by a small team of people in
- 24:40Leon and and there are twelve of us
- 24:42and it's it's great to have them there.
- 24:45It is possible to join us.
- 24:47We have a number of fellows that joined us
- 24:49from time to time and visiting scientists.
- 24:52So if you've got the opportunity
- 24:54and you'd like to do it,
- 24:56we can fit a couple of people in,
- 24:57usually into the office space we have.
- 25:02And it would be lovely to welcome
- 25:04people from Yale if we could.
- 25:05In terms of what we've done already,
- 25:08well, we've published digestive breast,
- 25:10soft tissue and bone female
- 25:12genital and thoracic tumors.
- 25:14The central nervous system volume
- 25:16is about to be stitched together in
- 25:19from the individual chapter proofs
- 25:21and it will go to the printers
- 25:23on the 12th of November.
- 25:25So it will appear on the website,
- 25:27probably towards the end of
- 25:29this month as well.
- 25:31In terms of the pediatric tumors volume,
- 25:34that is massive.
- 25:36It's the equivalent of two books,
- 25:38and it needs to be coordinated
- 25:40with quite a lot of the others,
- 25:42so it's proving quite a tough one to do.
- 25:44And and we've got the draft,
- 25:46but we haven't met yet.
- 25:48Managed as yet to get it through technical
- 25:51editing, so it is a bit delayed,
- 25:52but it is on its way.
- 25:55The urogenital male genital
- 25:57tumors is also impressed.
- 25:59That is with the technical editor
- 26:01at the moment and it should come
- 26:03out relatively early next year.
- 26:05I hope within Q1 or possibly Q2.
- 26:09In terms of the head and neck and the
- 26:11endocrine near endocrine and endocrine,
- 26:13they are being edited at the moment's ready
- 26:17for technical editing early next year,
- 26:19so they should be out sometime
- 26:22over the summer.
- 26:23And then the humours of lymphoid
- 26:25tumors volume is being written.
- 26:26Uh,
- 26:27and then we're about to start
- 26:29the skin and the I.
- 26:30We set our timescale for doing things
- 26:33at the beginning of the process so
- 26:35that that we could get the whole
- 26:37thing done within the five to six
- 26:39years that we felt was optimal
- 26:41and and that was backed up by the
- 26:44findings of a large survey that I'm
- 26:46sure some of you participated in.
- 26:48And again, thank you for doing that.
- 26:50And we're going to finish the whole
- 26:52series of the 14th volume on genetic
- 26:54tumor syndromes because that's
- 26:56becoming increasingly important that
- 26:57we felt we could not ignore that.
- 27:01The website now has a new look,
- 27:05and if you haven't seen it,
- 27:06I'd recommend getting onto it.
- 27:08If you can, you can preview it before
- 27:10you have to pay a subscription for it.
- 27:13It is a subscription website and we
- 27:15do sell the books and the reason for
- 27:18that is that this is a not for profit
- 27:20exercise that is completely funded by
- 27:23sales of the books and and the website.
- 27:27Now, yes, we could apply for grants and
- 27:30we could try and find external funding.
- 27:33But then that external funding would
- 27:35have a say in how we did things,
- 27:37and that's not something we want
- 27:39at the moment.
- 27:40This is essentially in the
- 27:42hands of its subscribers,
- 27:44so that's 60,000 people and it's
- 27:48very hard to make it anything other
- 27:50than what it is as a definitive
- 27:52classification on that basis.
- 27:57The actual write up for each tumor
- 27:59looks very similar to the book.
- 28:00It's just a single column across a text,
- 28:02but it's the same text, the blue numbers
- 28:05there are actually pub Med ID's,
- 28:07so when you click on one of those,
- 28:09a hyper link takes you straight to pub
- 28:11Med to the reference and to the evidence
- 28:14we've quoted for that particular statement.
- 28:16We also have whole slide images
- 28:18and in the breast, but we have
- 28:21whole slide images for every tumor.
- 28:23And when you click on it,
- 28:25you get a legend just as you
- 28:27would for anything else,
- 28:28and then you get into the slide and then
- 28:31you can go to very high power view.
- 28:33So I was asked to talk about
- 28:36the challenges and.
- 28:38I expected some of them and the
- 28:41expected ones included the fact that
- 28:43we needed to produce these volumes
- 28:45faster without compromising quality.
- 28:47We knew that was going to be
- 28:49something that was important.
- 28:50We also knew that whole genome
- 28:52sequencing was coming into mainstream
- 28:54diagnostic practice for some things,
- 28:56and XM sequencing for others.
- 28:59We knew that there was a lot of
- 29:01genetics that we had to get in.
- 29:03We kind of thought artificial
- 29:04intelligence probably a little bit
- 29:06too early for the 5th edition,
- 29:07but it has actually come into
- 29:09one or two points already.
- 29:11And it's certainly set to do more.
- 29:14We did think that perhaps radiologists
- 29:16were trying to take over from
- 29:18pathology in terms of some diagnostic
- 29:20entities that hasn't really happened,
- 29:22but we're very pleased to say that we
- 29:24do have a radiology Advisory Board
- 29:26that gives us an enormous amount of
- 29:29support in making sure the radiology
- 29:31within the books is as good as it can be.
- 29:34The radiologists actually
- 29:35don't have anything like it,
- 29:36so they're really quite interested
- 29:37in what we're doing.
- 29:40There was some unexpected stuff too,
- 29:41of course. Look, the confusing terminology
- 29:45within pathology is something that
- 29:47most of us have lived with and dealt
- 29:49with for most of our working lives,
- 29:51but we did have some really.
- 29:54We do have some really good ones and
- 29:55we are trying to reduce the confusion
- 29:58wherever possible because it does
- 29:59impact on patients occasionally.
- 30:01The best one we came across was,
- 30:03I think, in the digestive volume
- 30:04and it was this one inflammatory
- 30:07pseudo tumor like follicular stroke
- 30:09fibroblastic dendritic cell tumor.
- 30:11And all of us in the room kind of looked
- 30:13at one another and said, what is it?
- 30:15And and then looked at John Chan,
- 30:17'cause he's always got the answer.
- 30:18And and on very kindly turn around and say,
- 30:21well, it's an EBV positive
- 30:23inflammatory dendritic cell sarcoma.
- 30:25So we said, well, why did we call it that?
- 30:28And the answer was that we did,
- 30:30so it's one of the very few that we've
- 30:33actually taken essentially outside
- 30:36the system and made a change because
- 30:38we felt the name is just impossible.
- 30:41Uhm, we have a problem with Mitoses
- 30:45and the major problem there.
- 30:47I'll show you in a moment,
- 30:48but it's to do with standardized
- 30:51international units.
- 30:52We had committed very early on
- 30:55to use HGVs notation,
- 30:57so the huger notation for genes,
- 31:00mutations, fusions, rearrangements,
- 31:02alterations and sequence variants.
- 31:05And we said that we would do this.
- 31:08It proved to be quite a challenge,
- 31:10because although molecular pathology
- 31:12has become very common in some settings,
- 31:15in others, it is more challenging.
- 31:20It turns out that that we have some
- 31:22problems in terms of counting as well,
- 31:25particularly bases and histones,
- 31:27and we've had to publish a paper on
- 31:30that to produce a notation that works.
- 31:34Uhm,
- 31:34and then of course we have this
- 31:36problem of whether we call things
- 31:38variants or subtypes and what's
- 31:40histological pattern when it's at home.
- 31:42So there have been a few things and
- 31:45I'll go through a few of them just now.
- 31:48One of the first things though,
- 31:50was to think about evidence based pathology.
- 31:55When in the 4th edition, the books
- 31:58are essentially a consensus document,
- 32:00a consensus statement of experts and
- 32:04about 30 to 40 experts involved in the
- 32:08meeting that would produce the consensus
- 32:10based on what authors had written.
- 32:12And the question really in our minds was
- 32:14whether this was eminence or evidence.
- 32:16And the answer is it probably is evidence.
- 32:19It certainly is evidenced because
- 32:21those experts are expert for reason.
- 32:24Uhm, but here you've got someone
- 32:26who is extremely eminent.
- 32:28The future King of England.
- 32:30But I'm not convinced that you
- 32:31want him staring at a microscope
- 32:33looking at your biopsy.
- 32:34Or mine for that matter.
- 32:37In terms of of confusing terminology.
- 32:40I've already mentioned one.
- 32:42I'm going to just select one here
- 32:44and it's pseudo tumor.
- 32:45That's about halfway down.
- 32:46It's a term used to refer to
- 32:49any number of pathologists,
- 32:50both benign and malignant,
- 32:52that may produce a mass.
- 32:54It's imprecise,
- 32:55it's not a good term,
- 32:57and we've tried to extract it from
- 32:59the books and over nearly succeeded.
- 33:01There is one in one of the books.
- 33:03For those of you that want to
- 33:05go looking for it.
- 33:06But there are other things here
- 33:07that we've known for a long time.
- 33:09Things like carcinoid,
- 33:11which is potentially imprecise as well,
- 33:14but is still very much used clinically in
- 33:17the lung field and impossible to change.
- 33:20Certainly in this edition.
- 33:24In terms of assessment of mitoses,
- 33:26this was something that I first
- 33:28came across nearly 40 years ago.
- 33:30And I was really surprised to
- 33:31have to publish on it again.
- 33:33I have to say. Uhm?
- 33:37First of all, what do you call it?
- 33:39Well, it's a mitotic count.
- 33:40When you do it on a microscope,
- 33:42nearly always.
- 33:42And it's really a density measurement.
- 33:45So you are expressing the number term
- 33:48of mitoses per millimeter squared.
- 33:50Not pleased high power field
- 33:52as I'll show you in a moment.
- 33:55The mitotic index would be the
- 33:57number of mitosis is expressed
- 33:58as a percentage of the number
- 34:01of neoplastic cells present,
- 34:02and you'd have to count hundreds
- 34:04of cells in order to do it.
- 34:06It's definitely one for the artificial
- 34:08intelligence and and not for the human,
- 34:10I would suggest.
- 34:12Mitotic rate is actually the
- 34:14rate at which cells are entering
- 34:16mitotic phase of the cell cycle,
- 34:19expressed as a percentage
- 34:20of cells counted per hour.
- 34:22So it has a time in it.
- 34:24And that's not something you can
- 34:25really do in a form and fixed.
- 34:28Specimen.
- 34:28So in practice,
- 34:30pathologists use mitotic count but we
- 34:33often get the name and the numbers wrong.
- 34:36Why do we get the numbers wrong?
- 34:38Well,
- 34:39historically,
- 34:39we've tended to use high power fields,
- 34:42ignoring the fact that between microscopes,
- 34:45high power fields can differ by up to
- 34:48six times even at the same magnification.
- 34:51And the switch to digital
- 34:52pathology is actually not helped.
- 34:53It's paint things worse because
- 34:55the 400 times fields in digital
- 34:58systems are rectangular and
- 35:00they also vary in area and they
- 35:02can vary quite a lot in fact.
- 35:05So the potential for error is quite
- 35:07considerable and at times that could
- 35:09affect patient care or even diagnosis.
- 35:11It's solved really by the use of
- 35:15standardized international SI units,
- 35:16so size does matter and it's millimeters.
- 35:20So we recommend counting features
- 35:22like mitoses per millimeter
- 35:24squared with an indication of the
- 35:26area to be counted and the method
- 35:28used which can be hot spot or
- 35:30average to obtain the results.
- 35:33These kind of graticule's on slides
- 35:35are actually available very freely.
- 35:37You can get them from Amazon
- 35:39for about $13.00 each.
- 35:39If you haven't got one and like one
- 35:42there should be one knocking around
- 35:43the department somewhere I'm sure,
- 35:45or possibly several and.
- 35:48The Convention is to use a 40 times
- 35:52objective, but if you use a 10
- 35:54times IPS or a 12 1/2 times IPS,
- 35:56of course you'll get something
- 35:58different and it's pile squared.
- 36:00Calculate the area.
- 36:01You only have to do it once
- 36:03for your microscope.
- 36:04I always had it on a sticky label on
- 36:05my microscope when I was reporting
- 36:07and it was something that I
- 36:10referred to virtually all the time.
- 36:13In terms of counting mitoses as well,
- 36:16it's important to know whether you're
- 36:18doing an average or random count,
- 36:20which may not be all that random
- 36:22unless you use a random number
- 36:24generator to do it properly,
- 36:26or a hotspot method and the hotspot
- 36:29North method is what is generally used,
- 36:32so these are contiguous.
- 36:36If. Microscope fields around a hot
- 36:39spot where you found a lot of mitoses.
- 36:43It's a little bit hit and miss,
- 36:45but it's better than most other
- 36:47things and it's been shown to
- 36:49be in various publications.
- 36:53There are quite a few examples
- 36:55here of of tumors, and this is only
- 36:57looking at the first few books,
- 36:58so it's by no means comprehensive,
- 36:59but it's just a few examples of things
- 37:01where there is a problem and reassessment
- 37:04of mitoses is probably worth while.
- 37:07The other reason why it's worthwhile to
- 37:09reassess mitoses in in tumors is because
- 37:12it is very often used prognostically.
- 37:15And prognosis changes depending on what
- 37:17the treatment is and if the treatment
- 37:19of the tumor has changed overtime,
- 37:21then what was done previously in terms
- 37:25of prognosis is a bit of a problem.
- 37:28I used to teach a lot of ophthalmologists
- 37:31about retinoblastoma and I would
- 37:33start by telling them all the
- 37:34things that were bad prognostic
- 37:36factors for retinoblastoma patients,
- 37:38and then say at the end of the lecture right,
- 37:41you can ignore all that once
- 37:42you pass the exam,
- 37:43because actually all these
- 37:45patients get chemotherapy and
- 37:47they all virtually all get cured.
- 37:50In fact,
- 37:50we had one death in eight years
- 37:52when I was at Morefield,
- 37:53so it is something that has to be looked at.
- 37:58In terms of treatment as well as pathology.
- 38:03We have a little bit of a
- 38:05challenge with statistics as well,
- 38:06so most biological data is skewed
- 38:08and if you use a mean you've got an
- 38:11error there which you don't have.
- 38:13If you use a medium,
- 38:14so the median is preferred by
- 38:17statisticians with a range because
- 38:19it's not affected by skewed data.
- 38:21In terms of genomics and most of you,
- 38:24I'm sure we will know this, but.
- 38:28B RAF V 600 E UM is written
- 38:30in all sorts of ways.
- 38:32This is the correct way to write it,
- 38:34and it's really important that that's done.
- 38:37If it's done with sequencing and
- 38:39if it's done using an antibody,
- 38:40then it's still important to say
- 38:43B RAF P dot V600E if you can,
- 38:46simply because that then tells everyone
- 38:49that you're looking at the protein.
- 38:51And the beer after course of its
- 38:55approaching should not be in italics.
- 38:57We very often, though I don't know,
- 38:59and I'm sure some of you have you
- 39:01sit in the clinical meeting and
- 39:03someone asked the B raft positive or
- 39:05negative on the Melanoma completely
- 39:06missing the point about mutation.
- 39:10In terms of histones,
- 39:11the problem is that the methionine,
- 39:12the little green one here and gets chopped
- 39:16off during production of the protein.
- 39:19And what that means is that the
- 39:22antibodies are all named according
- 39:24to the numbering of the protein.
- 39:26Once the methionine has been taken out
- 39:29and not what you get on a sequencer,
- 39:32which will give you a 28,
- 39:34not a 27 or 35, not a 34.
- 39:37So we've suggested that instead,
- 39:39what one should do is put the
- 39:43histological number if you like in
- 39:46brackets and the genetics number in
- 39:48genetics derived number in as you
- 39:52would normally in a in the system,
- 39:55and for some reason I've got a
- 39:57little hyphen appeared there,
- 39:58which wasn't supposed to be there.
- 39:59Apologies for that. Uhm?
- 40:02The fusion genes.
- 40:03This is literally hot off the press.
- 40:06This hasn't even got a payment yet,
- 40:08but it's just come out in leukemia
- 40:10and it suggests that rather
- 40:12than the previous notation,
- 40:13which was very confusing for fusion genes,
- 40:17we should use a double colon instead
- 40:20as the current system of using a hyphen
- 40:25or a forward slash is actually used
- 40:29in lots of other settings as well, so.
- 40:33The clever people Hugo came up with,
- 40:35and Elizabeth Bruford is is one of them.
- 40:39Came up with this idea of using two colons,
- 40:41and I think it's going to take.
- 40:43We are implementing that within the blue box.
- 40:47If you're interested in genetics are awful,
- 40:49lot of resource is available.
- 40:51I would point out variant
- 40:52validated down here,
- 40:53which is actually quite a
- 40:55useful one and we do as well.
- 40:58Obviously use some of the other things here.
- 41:01Gene names and gene cards I
- 41:04use quite a lot as well.
- 41:06I want to spend the last sort of 10
- 41:08minutes or so talking about research needs.
- 41:12Uhm, because we have lots of evidence gaps,
- 41:14we know they're there.
- 41:15If you look for the word unknown within
- 41:18virtually any of the blue books,
- 41:20you'll find 150.
- 41:22Also instances of it.
- 41:24And those are the things we
- 41:25know we don't know.
- 41:29In terms of of evidence gaps then.
- 41:33We have all sorts of things that
- 41:35have come out of the blue books,
- 41:36so we can actually say right?
- 41:38There's a need for more genetic
- 41:40studies of neuroendocrine tumors.
- 41:41There's a need for
- 41:43computational studies of Chi,
- 41:4467 perhaps of mitotic count.
- 41:47And we need to know what there is.
- 41:50So this was a this.
- 41:52This little list came out of a
- 41:54meeting on neuroendocrine tumors,
- 41:55which led to the current classification
- 41:58of new endocrine tumors,
- 42:00which has been applied across the series.
- 42:08I'm a Scotsman and I'm sorry I've got
- 42:09to give you a little bit of burns,
- 42:11but there is a translation at the bottom
- 42:12for those of you that are having a problem.
- 42:14UM, facts are chiels at winner
- 42:16Ding a downer be disputed. Uhm?
- 42:19It's essentially an older version of facts
- 42:23that are things that you can't dispute.
- 42:29And. As Donald Rumsfeld put it,
- 42:32we have known knowns.
- 42:33We have things that we know we know.
- 42:36They are straightforward.
- 42:38They're not under any.
- 42:41Control the C in pathology or anywhere else.
- 42:44And there are plenty of those
- 42:45in the blue books,
- 42:46and it's sometimes hard to
- 42:48find a reference for them,
- 42:49because actually we know that true.
- 42:52Then there were the known unknowns.
- 42:55There are things we know we don't know,
- 42:58and those are the unknowns that I've
- 43:01talked about in the books so far.
- 43:03But there are also undoubtedly a lot of
- 43:06unknown knowns things that we've forgotten,
- 43:08and a lot of that these days has
- 43:10come from things like electron
- 43:12microscopy and ultrastructure,
- 43:13which is not very fashionable and
- 43:15and it's quite surprising how little
- 43:17of it gets into the blue box,
- 43:19but I have pleased to say that in
- 43:22the endocrine volume you'll find
- 43:24that does happen because it's
- 43:26still there still important.
- 43:29And then we have the unknown unknowns.
- 43:30The things we don't know.
- 43:31We don't know,
- 43:33and that's something that
- 43:36really underpins research,
- 43:38so by looking at tumors carefully
- 43:41by looking at good well call
- 43:44it well put together series.
- 43:47And doing properly constructed
- 43:49cohort studies with.
- 43:51Protocols before you start the study,
- 43:54we can certainly get a lot further
- 43:56than we do. I think at the moment.
- 44:00And in terms of improving research quality.
- 44:03Why should it have lower standards
- 44:05when it affects gonna potentially
- 44:06affect huge numbers of patients than
- 44:09we would accept in clinical practice?
- 44:11So in clinical practice you would not
- 44:14accept a sample into your laboratory
- 44:16that didn't have 4 identifiers.
- 44:18But you would quite happily accept that into
- 44:21a research lab with just one in many cases.
- 44:25Drug approvals require two independent
- 44:28confirmatory phase three clinical studies.
- 44:30And what does pathology need?
- 44:32Well. I think it needs levels of
- 44:35evidence the same as anything else.
- 44:37We struggle with systematic reviews
- 44:39and pathology because they have to
- 44:42be systematic reviews of high level
- 44:44evidence and we struggle with getting
- 44:47hold of independent prospective studies.
- 44:49Of independent cohort studies
- 44:51of sufficient size.
- 44:52Sample size calculations are
- 44:54rarely stated in pathology papers.
- 44:56They need to be.
- 44:58Uhm and withdrawn often to case reports,
- 45:01small cohort studies or expert opinion.
- 45:05And that's still evidence.
- 45:06But it's not very high level evidence.
- 45:12So to try and answer this,
- 45:14having put together a process for
- 45:17production of the classification of tumors,
- 45:19we thought it was important to try and
- 45:22support the other side of the coin through
- 45:25setting up the international collaboration
- 45:28for cancer classification research.
- 45:30Uh, what that's about is,
- 45:32UM, evidence based.
- 45:34Science about best practice,
- 45:37guidance about standards and accreditation,
- 45:41and about information systems as
- 45:42well to try and reduce the vast
- 45:45amount of data produced every year
- 45:47to something that's manageable enough
- 45:49to pull through into a blue book.
- 45:52And at the same time we can feedback
- 45:55the priorities and gaps that we
- 45:58identify during the bluebooks process
- 46:00into the sound of that community.
- 46:03And this seems to have hit a bit
- 46:04of a chord with a lot of people,
- 46:06and it is a collaboration of institutions,
- 46:08not individuals I should add.
- 46:10So if you would like to join us,
- 46:13I'm sure that would be a great,
- 46:15gratefully received a lot.
- 46:17R and we're very grateful to those
- 46:20that have helped to set this up.
- 46:22I'm just going to show you one project from
- 46:24it and this is called the WCT evidence map.
- 46:29And it's so WTTW classification of tumors,
- 46:34obviously,
- 46:35and what this allows us to do is to
- 46:39have a tool which allows us to examine
- 46:42the blue books to identify what the
- 46:45evidence is and where it's lacking.
- 46:48This is a stylistic
- 46:50interpretations of maps you get,
- 46:52and that's what a real one looks like,
- 46:53and I don't expect you to read it,
- 46:55but you can see the blobs that are red,
- 46:57that I'm afraid is the low level
- 46:59evidence and the little green ones are
- 47:01the ones you really want to see Blues.
- 47:03OK, but green is high level evidence,
- 47:05and in epidemiology there's
- 47:07remarkably little for some tumors,
- 47:09but of course it does depend
- 47:11on how common the tumor is.
- 47:12It depends on how much funding
- 47:14has gone into researching it,
- 47:16and all sorts of other things,
- 47:17so it's not surprising.
- 47:18But we got this,
- 47:20but I think it's important information to
- 47:22know so that we know what we don't know.
- 47:28I'm nearly finished,
- 47:29but to just break come back to the
- 47:32site of pathology reporting system
- 47:34and talk about the mock up for The Who
- 47:37psychopathology reporting system volumes,
- 47:40which will be coming out next year.
- 47:42And as you can see on the front,
- 47:44we've got the World Health Organization IIRC,
- 47:47and we've also got the
- 47:50International Academy of Cytology.
- 47:52It will look a little bit different
- 47:54and it will have this. Uh.
- 47:56I think it's it's probably fuchsia,
- 47:59but we have a layout editor who
- 48:02is far better at color than I am.
- 48:05And she thought that was probably quite
- 48:07a good idea to have something that
- 48:09defined it meant that you didn't confuse
- 48:12it with a blue book on the bookshelf.
- 48:15We are still very much interested
- 48:17in working on AI,
- 48:19and one of the things that is fascinating
- 48:22to me and it's it's part of some
- 48:25work I started when I was in Warwick.
- 48:27Is that there is?
- 48:29Clearly,
- 48:30a relationship between the genetics
- 48:31of tumors and their histopathology.
- 48:33All there should be.
- 48:34Because there's a relationship,
- 48:36but doing the genetics of tumors
- 48:37and their behavior,
- 48:38so we should be able to see that
- 48:40reflected in this to pathology.
- 48:42It's actually been quite a hard
- 48:43thing to demonstrate,
- 48:44but here in colorectal cancer using TCGA
- 48:47data we've been able to do just that,
- 48:51and the rock the rock curves here.
- 48:53The receiver operator characteristic
- 48:55curves and not too bad the area
- 48:59under them is about .89 best,
- 49:02which is almost at the point
- 49:03where you start thinking about
- 49:05putting it into practice,
- 49:07so it may be possible to
- 49:09identify some of the genetics.
- 49:12That we need to treat patients
- 49:14with from artificial intelligence
- 49:17based assessment of histopathology.
- 49:20And the other thing it tells us is
- 49:22which are actually the important
- 49:24features that we talk about when we
- 49:27look down a microscope for defining the
- 49:29characteristics of the patients tumor.
- 49:34So I'll finish by talking
- 49:36about how how you can help.
- 49:38First of all, if you can provide
- 49:40the evidence by doing research,
- 49:42that's a big help.
- 49:44Uhm, and and don't think that when you
- 49:46published the paper that's the end of it.
- 49:48It's a question of taking that research and.
- 49:52Pushing it in the direction where it will
- 49:55get into practice if at all possible.
- 49:57And then evaluate the evidence.
- 49:59Systematic review learn how to
- 50:00do systematic review properly,
- 50:01and it's not simple.
- 50:03You have to learn how to write protocols
- 50:06for it and assess evidence for bias,
- 50:11particularly.
- 50:12And it is quite a challenge to look
- 50:14through large numbers of papers.
- 50:17And then if you buy the books or the website
- 50:20you are actually funding the evidence.
- 50:21So thank you very much indeed for doing that,
- 50:24because that keeps the whole thing going.
- 50:26And finally, let us know what you think.
- 50:29You can give us feedback on the website.
- 50:31You can certainly email us a lot of people.
- 50:34Do I get an awful lot of emails and
- 50:36we're always open to receiving cases
- 50:39which are better representative
- 50:40cases than those in the books.
- 50:43And if course, if you find any errors,
- 50:46do tell us because that's
- 50:48the way we get them fixed.
- 50:50So in conclusion,
- 50:51there is a need for all cancer
- 50:53diagnosticians to contribute to
- 50:55research to gather the evidence
- 50:57a patient needs and to evaluate
- 50:59that evidence for use in practice.
- 51:02Our diagnosis underpinned the
- 51:04management of individual patients
- 51:06Cancer Research and epidemiology.
- 51:08It's pretty important stuff.
- 51:11In terms of implementation
- 51:13of academic research,
- 51:14pathology is almost unique.
- 51:18In being able to do that itself
- 51:21through the WTO classification of
- 51:23tumors which provide the international
- 51:25standards for knowing motors,
- 51:26you can't do that with drugs and you
- 51:29can't do it with a lot of other things.
- 51:31Which gulf governments really
- 51:34are the arbiters of?
- 51:36So we have a joint responsibility
- 51:39to ensure the accuracy of the
- 51:41classification and to fill gaps
- 51:44and knowledge wherever possible.
- 51:46So thank you for your attention.
- 51:49This is the tower which I
- 51:51are currently inhabits.
- 51:52It isn't in great condition and the
- 51:55French government is very kindly building
- 51:58us a new Center for the International
- 52:01Agency for Research on cancer,
- 52:03which will really be a focus
- 52:05for international Cancer
- 52:06Research around the world.
- 52:08And a nice view of of of Lyon in the summer.
- 52:12And thanks to my team in Leon,
- 52:15which has worked so hard,
- 52:18particularly on the 5th edition.
- 52:20And I'm also grateful to two
- 52:22distinguished visitors, Valerie White,
- 52:24from Vancouver and Delani Luca Hattie,
- 52:28from Colombo, Sri Lanka.
- 52:31Thank you very much.
- 52:34Thank you so much Ian,
- 52:37that it was really a pleasure.
- 52:40To understand what goes behind the
- 52:43scenes in producing these beautiful,
- 52:46extremely affordable and
- 52:48extremely user-friendly books,
- 52:50I do have a question.
- 52:52Since you mentioned how difficult
- 52:55it is to gather evidence.
- 52:58So in pathology,
- 52:59most of the work we produce is
- 53:04retrospective and observational.
- 53:06And it's really getting harder to get.
- 53:11Follow up on many of these patients,
- 53:13so is there any future for
- 53:17retrospective and observational data?
- 53:20Yes, I think I think there is an I
- 53:24mean the the. The there's certainly,
- 53:26you know it's very easy when you
- 53:28look at levels of evidence and you
- 53:30say Oh dear opinions worth nothing.
- 53:32Therefore, the review I published last month,
- 53:33I might as well not have bothered.
- 53:35I did a case report last year
- 53:37with one of my juniors.
- 53:38I shouldn't bother doing that either.
- 53:39That's not the case.
- 53:41Actually, my sixth case report my
- 53:446th postmortem autopsy when I was
- 53:47training led to the withdrawal
- 53:49of a drug from the market.
- 53:50It was dangerous.
- 53:52So Uhm, case reports matter.
- 53:55That was a case report.
- 53:58And you can learn an awful lot
- 53:59from some case reports.
- 54:00We talk about the end of one
- 54:02trial in in oncology quite often,
- 54:04so there are things that we can do
- 54:07with case reports with small studies.
- 54:09Even better if we can band together
- 54:12internationally and actually get bigger
- 54:15studies put together on samples that
- 54:18we collect prospectively with a protocol.
- 54:21And then we've got a chance of getting
- 54:24some proper funding into it as well.
- 54:26And and we probably find we can
- 54:29go beyond pathology and pathology
- 54:31is simply the study of disease.
- 54:33So how we do it?
- 54:35Doesn't really matter whether
- 54:37it's with a microscope.
- 54:39Or an MRI.
- 54:41Or sequencing device doesn't actually matter.
- 54:46What we what we need to do is
- 54:48know what our questions are
- 54:50and what we were trying to do.
- 54:52Classification in its own right
- 54:54taxonomy is actually something that
- 54:56I think matters and which we can.
- 54:59We can almost certainly do better
- 55:02with than we are at the moment
- 55:05and get people to fund.
- 55:07So I think the future is
- 55:10pretty bright actually.
- 55:11That said,
- 55:11you can still do an awful lot of
- 55:13the microscope there, graticule.
- 55:16Uhm? Thank you, there is a
- 55:19question posted in the chat.
- 55:22Is there an electronic
- 55:24version of these books?
- 55:25For example, is the database
- 55:28behind it is available for download
- 55:31and use in electronic systems?
- 55:34Is there an API for querying the
- 55:38latest version of the database via
- 55:41a public or paid Internet access?
- 55:45Right, so that that that's a
- 55:48that's a multiple question.
- 55:49It's a good one too.
- 55:51The answer is that it's not easily available,
- 55:54it is a SQL database.
- 55:56So theoretically, yes, you can do it.
- 56:00We've got the, uh, electronic system
- 56:03going in terms of the website,
- 56:06so the website is is searchable,
- 56:08so you can do searches on
- 56:10the website and it's not.
- 56:12A sophisticated, not sophisticated,
- 56:13perhaps as it might be.
- 56:15But it could become more sophisticated,
- 56:18and I think we'd be very open
- 56:20to working with people on that.
- 56:23In terms of what we have to safeguard,
- 56:25clearly we have to safeguard the
- 56:26income of the of the program.
- 56:28'cause if we don't,
- 56:29we've got a problem.
- 56:31But there are.
- 56:34You know there are examples of where
- 56:36that's been done very successfully,
- 56:37for instance Genomics England have done
- 56:39it with their data so you can access that.
- 56:42It's just been done as well for a
- 56:45very large pathology set up in the
- 56:47middle of England called Path Lake,
- 56:49which has half a million annotated
- 56:52whole slide images. So there are.
- 56:57There are ways of doing it.
- 56:58The short, the short question.
- 57:00The short answer though.
- 57:01Sure.
- 57:03So I say no more questions and
- 57:06it's time to wrap up and come.
- 57:09I would just remind the audience that
- 57:13you are welcome to volunteer contact Dr,
- 57:17Cree and volunteer.
- 57:20In data analysis, or in any way you
- 57:24think your talents can be used.
- 57:28I hand over to Doctor Lu our chair.
- 57:32Yeah, thank you and I will
- 57:34share my screen now.
- 57:36Thanks talk to create for your
- 57:38coming and I I think unfortunately
- 57:40we couldn't do it in person and
- 57:43couldn't present you some token
- 57:45to you know on behalf of the
- 57:47department and our faculty.
- 57:48So I think you know we come up with this.
- 57:53Play, you know
- 57:55it will mail it will. So this is,
- 57:57uh, we're not just giving you a
- 57:59virtual plug, it's real well alright
- 58:01yeah it will be a real life this is a
- 58:03picture of that and I hope you know this
- 58:05we just you know really you
- 58:08know express our gratitude
- 58:09and if we are leadership for this,
- 58:11you know you know great book
- 58:13which is making such immense
- 58:15impact on pathology practice
- 58:18and I think it also this is
- 58:20just a reminder, you know
- 58:21we are ready to, you know to work with
- 58:23you to collaborate. And best wishes for
- 58:26the next. You know, the 5th
- 58:27edition of the Blue Book and
- 58:30thank you very much and saying,
- 58:31you know, hopefully we can
- 58:32see you in person sometime.
- 58:34You know either in your place
- 58:36or in our place in the future.
- 58:38Thank you, appreciate and I will say it.
- 58:40You thanks doctor.
- 58:41You know Manju Prasad,
- 58:43you know she this is her
- 58:45idea. So I'm just kind of presented
- 58:47her idea in this is great that
- 58:49you know you know idea to get. You
- 58:51know they will this you know present.
- 58:55Thank you very much indeed.
- 58:56It's been a great honor
- 58:57and a privilege to be here,
- 58:58and I've enjoyed talking to
- 59:00some of you over the afternoon
- 59:02and my afternoon anyway.
- 59:04And I hope the rest of the day for you
- 59:07goes well and I'm sure we will be in touch.
- 59:10Thank you.
- 59:11OK, thank you very much.
- 59:12Thank you.