Videos Going up - Groningen 2015

The videos have started to go up from the conference in Groningen in May 2015. The delay was due to different publishing rights etc but this appears to have now been resolved. Happy to say that my presentation is on there and I think I did ok. 

www.dupuytrens.tv

Hahaha it even looks like they call me Dr Gary Manley... So that makes it official right? 

https://www.youtube.com/watch?v=splC4aATa3g

"Dr. Gary Manley "The patient's view: Ledderhose Disease" 2015 Dupuytren Symposium"

The videos make a great resource for patients and doctors as there is such a wealth of knowledge on there. If anyone has any feedback on what they would like to see then get in touch and we can start targeting the next symposium. 

International Dupuytren's Symposium - Day 2 - afternoon

Radiotherapy:

Prof S:

Looking at the whole body, look for feet, shoulder, privates, and hands not each thing as an individual item.

Radiotherapy can prevent progression in non-cancerous tumours and there are many different fibroma conditions. The radiotherapy impacts both proliferation and inflammation and this is how it can work on DD / LD. So radiotherapy can impact the cells as they are proliferating so quickly that the radiotherapy causes DNA damage that causes them to go into an apoptotic state rather than continuing to replicate.

TGF-B is very sensitive to radiotherapy and is known to be involved in the development of the cells from stem cells to postmitotic state PMF. This has been shown in science journals and cells basically are forced to skip the step in which they are proliferating and in which they cause DD.

Patients that are progressing, so therefore have active DD / LD are those that can be used to determine if patients should be treated. To be clear radiotherapy cannot be used in the latter stage of the disease, but can it be used post-surgery to prevent it entering the latter stages again. For the above to work we need to know what is progression so we can determine what is the right course of action. Increasing symptoms, cords, nodules itching etc are good signs.

If radiotherapy is used at an early stage it can delay or even stop progression. Published data shows that there are some responses to this in the different stages of DD and the later stages of DD should not be treated with radiotherapy but in the initial stages there is a good response to radiotherapy, especially in stage 1.

There have been several different techniques as to what is the best, and comparitive studies show they work but the favourite is 3x5gy done twice over 2 different weeks separated. Random between 2 schedules and controls

3 groups - 0 gy, 21gy (7 days in a row) or the now standard 30gy treatment.

No difference between electons on ortho-volt. There were no difference between the groups in terms of other factors.

20% of patients had a remission

53% were stable  in all RT patients.

Only 8% of patients in the 30gy group went on to have surgery..

Surgery is possible after RT with no extra complications. 12 week break is standard. Radiotherapy with lower doses does work if patients are concerned but it doesn’t work as well.

Radiotherapy used post op in patients with DD in PIP joint.

Ledderhose results skipped!!!! This was due to time constraints so I understand even if I am annoyed.

In cases of Ledderhose 80% of patients see reduce of symptoms and can be done post-operative and can be considered after multiple surgeries. There are several patients that have relapsed and in a different region they are happy to repeat, if there is a relapse in the same area then there can be a third week but going on beyond that is not great.

One key thing is that the dose is above 2gy, so 3gy x 5 or 5gy x 3 can work.

This was a very interesting talk and I knew most of it but it was great to hear the discussion between the surgeons and Prof S, his answers were mostly good.

Next was my talk, gulp.

Overall I think it went well and the basic results that I commented on were:

There is a very high number of female patients, in fact more so than in women and this could be real given the degree of deviation from the norm, however it could be a limitation of the survey, should take into account for the book how many patients have been self-diagnosed. In my experience there is a higher number of women, one doctor commented that many women who think they have nodules have hammertoe and many men who do not think they have Ledderhose in fact do have it. In hindsight I would argue that most of the patient participating in this survey are knowledgeable and most have Dupuytren’s so have probably been checked for Ledderhose, or at least should have been, so if the numbers are biased then it is because doctors are not checking up as they should.

The usual conditions are related.

Radiotherapy is the best treatment option as far as patients are concerned for Ledderhose. No other treatment option even comes close and no doctor even questioned this result. I got in my point about the lack of Ledderhose information and the lack of talks that even consider Ledderhose over the last 2 days...

After this point I did miss the next 2 posts in a post talk buzz but both Dr Bojaj and Anna both said well done on the way back to my seat which was nice.

Have to admit that despite nothing really being on the line for me my heart was pounding and I was a little nervous (though not much really) and I think this is because I wanted to do everyone proud, everyone who has taken part in the survey deserves me to put their point of view across. If anyone would like a copy of my powerpoint presentation then just ask, happy to provide. Certainly if you have Ledderhose then the graph on the treatment options is worth taking to any doctor you see that doesn’t approve of radiotherapy.

The next talk I have notes on is the one on Peyronie’s. To be fair this is probably a talk you can avoid watching, unless you like seeing surgery pictures and you can guess what they look like. Also mentioned the use of Collagenase on the treatment of this condition.

I am not sure what the last mini session is on but think it is mostly going to be 2 interactive sessions on research, first science research and then clinical research.

I will post this as an update now as I am unsure whether I will make many notes on the last session as I am not sure how relevant it will be to me, but I will do my best to give any input that I can and provide you with any output that I can.

International Dupuytren's Symposium Day 2 - Morning

....

Most recurrence will happen in the first 2 years, hopefully this means that I am past that point. They also look at patient satisfaction in terms of hand function in terms of Dupuytren’s patients, I think this is a great measure to use when treating DD patients although it does mean that you are relying on patients having similar goals and would love to see a similar study for Ledderhose. How many Ledderhose patients are happy with foot function after radiotherapy and surgery etc. For DD they did look at degree of contracture and other variables both pre and post operation to see whether there was any linkage between these and patient satisfaction which is great to be able to use as a predictor for success in surgery / PNF.

Much higher number of men were happy with their degree of function compared to women and nothing else was related (well may have been but i missed it). Not surprisingly those who had a more successful surgery with less complications were more likely to happy. Men were 2.5x more likely to be happy, this seems amazingly high and it does make me wonder about thinking more of the female side of this. Could the high numbers of men in most studies, including surgery, bias the results to be more favourable.

A fair amount of this session was on patient satisfaction and how to measure it etc, this was stuff that was not overly relevant to me, it is interesting to see that around 25% of patients do not think that the output given from their responses to surveys actually reflects how they feel about how their treatment went. Personally for me the most disappointing thing was the poor patient response rate, around half didn’t fill it out, come on patients when a doctor gives you a questionnaire fill it out you will be helping all the other patients out there by improving the results of studies.

We then moved on to looking at PNF a lot. Good for me as my Dupuytren’s knowledge is severely lacking as I am very focused on Ledderhose as this is what I have and know well so I haven’t looked at PNF. The first talk was by Gary Pess and his thoughts and tips on the use of PNF and Collagenase, this was interesting as he was someone I was chatting to for an hour or so at the dinner the evening before! Great to have made these contacts and hopefully can put them into good use in the future.

He prefers to treat early with minimally invasive options. Good to hear of a doctor that says that patients should be treated early and aggressively even if RT wasn’t mentioned. After all if treated early you are getting in there before they are losing too much function and he said that it worked better in terms of time until it comes back. Interesting to hear that, but I guess you are destroying a higher percentage of the disease tissue? I mean if you have a huge lump you will damage / remove 10% to break the cord, if you treat early you might destroy more like 50% and therefore it will take longer for the disease tissue to recover. Hopefully I can get some notes done on this to ensure that you can check your doctor knows what he is going, Gary Pess has been going this for a long time so if you are going to have Collagenase or PNF then I really recommend watching the video of this presentation as there is so much great information.

PNF in recurrence of Dupuytren’s - PNF rates can come back up to 85% of the time and the question was can it be done again and again to avoid having to have full surgery. PNF postones limited fasciotomy for around 4 ½ years and up to a fourth procedure it seems to work as well as a first procedure, but after this has reduced usefulness.

Dupuytren’s Treatment - Where are we now:

Are there too many options, they all have different merits and drawbacks and from the start radiotherapy was at least mentioned along with a few other options we had yet to hear about. It was interesting to get a brief history of Dupuytren’s and gives a good overview of it for anyone that hasn’t heard it before.

Steroids - Used in nodules but not cords

Radiotherapy - He didn’t give a good overview of this, just said radiotherapy can cause fibrosis. Just shows not looking at the data and talked about burning holes in hands as with breast cancer, the doses and treatments are different. I can just imagine the reaction that the active DART members are going to have when / if the watch this presentation on YouTube. .

NF and Collagenase - Not for super advanced condition.

Chemotherapy and Gene therapy - Didn’t go into detail

Also quoted the condition as being painless, from what I have heard about DD this is not always the case. Overall the talk was good but it was clear he was a surgeon with strong surgeon views and as I was sitting through it I was hoping that some of the RT doctors for example might be able to question him at the end.

Things then went into a bit more detail and started looking at steroid injections (they can actually be useful when used with NA/PNF) and can delay the recurrence of the condition.

There was another talk on PNF against collagenase (a very active area at the moment, probably due to the money being pumped into Xiapex) and in this case they found no real difference between the two different groups.

Comparison Xiapex with Limited fasciotomy and again there was no real conclusion.

There was a talk on the TEC technique and whilst it sounds like it could be interesting I recommend watching the presentation as the presentation was do at a very rapid pace, I think they were reading from a script and reading it quick! But the results suggest good functional results. I hope I am not being too critical of the speaker given that I will be standing in the spot later today. To be fair she finished bang on time and would have overrun had it been delivered at a slower pace, I guess less is more.

At this point I did start to struggle to keep up with the reports to some extent. I guess a combination of it nearly being lunch-time, having done a 6 mile run and thinking about my talk all played a part. Still I will do my best.

The next talk was looking at the microanatomy of the hand / finger. They are looking at some fibres that are all intertwined in the forming structures which is of course of great interest for these conditions. The idea being that these structures could form cords, I suggest if you are interested that you look up the speaker giving the conference from the notes.

Next 

What is the natural course for patients with primary DD came up next. The idea was to track patients every 6 months, nodules and cords (no mention of looking for Ledderhose??) and they have done this for 2 years at the time of the talk. Had around 250 patients with around 16% of fingers showing contracture. They found that over time the patients stayed stable in terms of the size of the nodules and cords and the angle of the fingers. The changes looked at were minimal so they did some fancy analysis that I didn't understand. Basically there were patients that were stable, increased in disease and decrease in disease and that the decrease was cancelling out the increase (I think) when looking at the numbers as an overview.

Basically they showed that in some cases the condition is not progressive. Of course this is a factor for radiotherapy as if a patient is not going to progress then you do not want to treat with RT when it is not required. A valid point and every more shows that if we can find a marker to show it is aggressive then we know to treat early and perhaps with RT (of course depends on studies etc).

Then we started to go through some recurrence papers / talks. A big problem is that you compare different papers and with DD there have been 40 different descriptions and you can vary your data to show recurrence from 2% to 86%, an extremely important report to get more consistency. After all there are many people championing radiotherapy on the claims it has less chance of coming back but perhaps it uses a different description. Certainly check out this as they had a group of experts and came to a consensus as to what we should call recurrence. This was the talk but Ruuf Selles. One aspect I didn't like is that it was, at least to some extent, on the functional aspect of degree of contracture on the hand. Surely the disease is there if there are nodules and cords, certainly this has no application to Ledderhose where you don't get contracture. I agree that it may not be important for DD where the degree of contracture and therefore function is the most important thing but it just would have been nice to acknowledge the nodules and cords as this is when patients (or at least I would) go to my doctor and therefore I would say the disease has come back. It was not included because (surprise, surprise) the presence of nodules and cords is not an indicator for surgery and some treatment release the fingers but do not remove the cords etc.

Does skin grafting reduce recurrence. As best I could tell it does but there are of course other factors that need to be taking into account when using this.

Later on:

Looking forward to this afternoon as I have seen that Professor Seegenschmiedt is doing a lecture on radiotherapy and he includes a section on Ledderhose, can’t wait and look forward to the discussion of this section as all the surgeons surely cannot deny proper clinical data from him and the obvious results from the patient survey that I will be presenting.

Overall another good session and for me second favourite to yesterday morning.

International Dupuytren's Symposium Day 1 - The Afternoon

The afternoon session kicked off with a genetics session, having studied molecular genetics at uni this really appealed to me, even if I was not sure on their main aspects as I was more molecular cell biology person and the statistics is a bit daunting.

Of course for Dupuytren’s this is vital as there is some genetic elements to the condition and if you know the genetics you can in theory more easily predict the biology that you need to look at to get results that are relevant to the condition.

There was some great background in the first talk which I am happy to say I remembered in good detail. Details on things such as SNPs and alleles. A good background for many and certainly will help when the presentations are published on-line.

One of the papers put the genetic risk at 80% (not inheritance there is a difference) leaving room to talk about trauma.They found some interesting results including the Wnt pathway, inflammation and transcription factors. One of the genes they mentioned was SFRP4. From a quick Google this looks interesting as it has previously been shown to play a role in cancer and apoptosis and a change in apoptosis could easily be relevant to any tumour. Must admit that this session didn’t give me as much of a buzz as the previous session, but this may of been because I was expecting some sort of genetic break-through but if we knew that then we would all know about that.

EPDR1 is another protein they mentioned. All I could tell from this section was that the protein is highly conserved and highly expressed throughout meaning that it is important, especially in those with European heritage which links nicely with Dupuytren’s and that their future work will hopefully unveil a functional reason for them pinning down this protein.

“The protein encoded by this gene is a type II transmembrane protein that is similar to two families of cell adhesion molecules, the protocadherins and ependymins. This protein may play a role in calcium-dependent cell adhesion.” http://www.ncbi.nlm.nih.gov/gene/54749

Of course the bottom line is that we still cannot determine the current genetic risk. The other factor that I found interesting was a sibling based study which I had missed seeing before, this showed that if you have the condition your siblings have a much greater chance (around 5x the risk) of getting the condition compared to the general population.

There is of course also the trauma side as I mention above, there was a study in this session looking at hockey players and I reckon you would see the same when looking at other sports such as cricket players and it has been previously shown that rock climbers have an increase. Interestingly the results were actually looked at from the point of view of vibrations causing an increase in risk rather than trauma, I would have thought that it was a combination of the the 2 and to be fair they did cover this in their discussion.

Associated factors was also looked at, with diabetes being looked at in this case. They raised some interesting points, again having to age control the control group. Their results were done from collating data from previous studies and analysing them to statistically correct for different factors. Basically for now their conclusion was that diabetes and Dupuytren’s are linked.

There was then a conversation on whether splinting was good or not. Can it be used to prevent contracture or post-op to make sure the finger stays straight and what sort of splinting should be used. If this is something that you think would be good for you to view I recommend watching the YouTube Video. Interesting that the surgeons are so happy to readily admit the high recurrence (can’t exactly deny it) yet it is still the main treatment option used around the world.

Not sure that I am going to have too much more to write up on this session because a lot of the information was very specific and the outcome was the result of a lot of statistical analysis which I don’t intend to go into in any detail.

The next session was on Collagenase, this session added to my frustrations in terms of lack of mention of Ledderhose. Mine is the only Ledderhose specific talk and throughout the day it was barely mentioned by anyone else other than in passing. There was the same number of talks on frozen shoulder as there was on Ledderhose, I don’t mind that but there could have done with being a few more on both, but then again the talks were really crammed in and it is amazing that so many people are available to talk on these conditions in the first place.

It was interesting to hear, that as in a lot of things, it came around by accident. The treatment was initially suggested for something else but went to the right person at the right time and that the act of snapping the cord came about when after treatment with CCH the fingers hadn’t straightened and the doctor went to shake a patient's hand and the cord popped. There is also part of the political side, that the drugs needs commercialisation and money to get off the ground, the drug needs to be able to make money, we all know that but interesting to hear another side of things. One of the things that shocked me the most was the gender bias in one of the studies. A whopping 83% of the people getting CCH injections were men, so either the men progress more with Dupuytren’s than in our survey or men really are significantly more lazy and aren’t doing the survey. Also lots of videos of fingers being released after injections, the pop of the finger is not the most pleasant of sounds! He did cover the side effects including skin tears and recurrence, which was at least 13% after a few years.There were many interesting points about the different factors such as dose, use of local anaesthetic and time from injection to finger extension.

One person used the presence of Ledderhose in 43% of patients as a case for them being severe cases, at least that was how it came across, that is certainly a high number but I think if all DD patients were checked we would find a high number of Ledderhose patients.

There are still concerns about the quality of data in the USA for radiotherapy, which is something that I know that there are many patient groups trying to address and it sounded like the doctors here wanted to address it as well. The doctors here all actually seemed positive about radiotherapy and it is just the geographical distribution of the surveys that are the issue.

Overall I think that an entire session on these injections was overkill, nevertheless is was still very informative and I appreciate that since the last symposium in 2010 there has been the most development in this treatment option.

Looking forward to tomorrow now with my talk to be given in the afternoon and hopefully I can convince a few people that radiotherapy is a great treatment option for Ledderhose and if I can’t then perhaps I’ll run round the room a few times to prove my point?

The whole day was fantastic and every talk was interesting and all the presenters did a great job.

(My picture wouldn't upload!)

International Dupuytren's Symposium - Day 1, morning

In Summary it was great to see so much interest and so much work going into these conditions, even if almost everything is focused on Dupuytren’s most of the work will have cross over with Ledderhose.

Note this is just an overview and I will try and go into more detail where possible.

The first session was really all about the different processes in different countries, mainly looking in USA, Germany and UK as this is where most of the patients are. There were some interesting points coming through on current trends and the increasing application of collagenase and gradual decrease in open surgery.

One point that interested me was that in the presentation Wolfgang gave it was clear that radiotherapy is actually a good treatment option for DD (as expected) in fact it was one of the top options. The next talk showed that patients, at least those that have had surgery, rank decreasing recurrence as their priority and I know this would probably be true for Ledderhose patient as well. Do these 2 observations combined mean that if you offered these patients the chance of radiotherapy at an early stage where recurrence would be low and their main other tissues such as side effects would be low surely they would take it?

The second session then moved onto a much more scientific point of view. Looking at the different markers in Dupuytren’s cells and how they can have an impact on the development and treatment of the conditions. I took a couple of main points from this:

1. There is a clinical trial on using anti-TNF to treat the early stage of Dupuytren’s.
2. I would like to follow up the above by contracting this person and seeing if they would be willing to expand the scope to include Ledderhose, certainly think we can get the patient numbers required.
3. There is lots of interesting research being done and lots of discussion happening, patients should take some heart from this.
4. DD cells can be problematic as they do not grow in normal culture environment in the same manner as other cells and this is an area which probably requires improvement and is being worked on.

There was lots of healthy debate in this session including:

1. How to best control experiments, age groups etc and later onset of DD in control group.
2. Does Estrogen play a role as some observed that this treatment increases odds - could this be linked to the later onset in women.
3. Should science be looking more into the aggressive condition, these are the patients that are then more likely to go on and need treatment.

I think the final point is again interesting from a radiotherapy point of view, in that it is in these patients where perhaps RT is worth a go sooner rather than later, especially in cases of DD where the hand can only be treated before contracture has not yet started. Imagine if we could come up with a marker, yes you have high risk of LD / DD and you are showing symptoms and RT helps (assuming a study shows that radiotherapy is a / the most beneficial treatment option for these patients).

Certainly a fascinating and enjoyable start and a lot to be learnt. Time to build contacts over lunch and looking forward to more this afternoon.

I already have 7 pages of typed notes and sorry for any typo's as I am writing this on the go, hopefully I will have some pictures up and about for the post covering this afternoons sessions.

About time for an Update:

Things have been fairly quiet on the blog recently, this is not because of a lack of motivation or anything like that but purely because there is not a huge amount to do nor do I have much time at the moment to give to the blog, though I am always finding time to help any patients that contact me.

I am still busy and active on the Facebook groups, both the Dupuytren’s Contracture one and the Dupuytren’s, Ledderhose and related conditions group. Both are full of useful and helpful patients that are making a different to other patients and all share a lot of information. There is also progress on the patient survey analysis. The Ledderhose section is now all but finished with just a few minor tweaks required. The results are interesting and the symposium is starting to approach rapidly.

Many people of the group raise some interesting questions and some good points, one of the end results of this is that we have created another survey. This is only a short survey and it is just looking at conditions related to Dupuytren’s and Ledderhose. Many people think that there may be links between other conditions that they have and Dupuytren’s, I would guess that in many cases it is just going to be that they are mostly conditions associated with people over the age of 40 and this could be the link. Please fill out the survey at the below address:

http://goo.gl/forms/hZXa5q2HRk

The symposium is in May and the details can all be found on the International Dupuytren’s Symposium website and there is now a schedule as to who is going to talk when, I am one of the last talks so better make sure that my talk is interesting enough to hold their attention at the end of the second day.

http://dupuytrensymposium.com/2015/

http://dupuytrensymposium.com/2015/InternationalDupuytrenConference_Programme_V3.pdf

I now have my flights booked, accommodation booked and I have plans on what trains I am going to get etc. The conference should allow me to make some really helpful connections and have access to the current research.

In fact the location looks really good and I am looking forward to doing the presentation, even if it will be in front of a lot of doctors. Hopefully there will be more surveys on the way or some other way we can all collaborate to generate useful data that is going to help patients. Touching on the location again there is a park nearby so I am hoping to get out for a run whilst I am over there.

On to me…

The running has been going really well since Christmas and combined with a low-carb diet I have not only smashed my 1mile and 3m(/5km) personal bests but I have also lost nearly 4 ½ stone (I still have a little way to go to get down to my target weight but very pleased with my progress so far). I cannot claim that all the excess weight was due to my foot but the weight I am now I have not been since my foot got bad and in another 7lbs I will be the lowest I have ever been as an adult.

I have been very impressed with how well my foot has coped with the excess demands that I have placed onto it and on only last week did it struggle. To put things into perspective in 2012 I couldn't walk without a stick and significant pain, even last year I could feel it after most runs (perhaps to some extent due to the weight?) and last week I managed the following: Saturday: 30 minute hill runs, Sunday: 2 hours badminton playing 1 hour coaching, Monday: 20 minute run, Tuesday: 2 hours walking and 2 hours badminton, Wednesday 30 minute run, Thursday 1 ½ hours badminton, Friday 2 hours badminton.

At the end of that not only was my foot hurting the most it has in a long time but I was knackered, luckily the weekend was mostly spent resting and now (3 days later) my foot feels fully recovered and I am having no pain at all and will try a short run today and I have badminton again on Thursday. To be fair it is unusual for me to do quite that much and although I am getting fitter it is a good reminder that I need to take my foot into consideration and as much as I want to run a marathon one day I have to make sure that I build up gradually and know that it is something that I may not be able to do. My target for this year is still to run a 10k in memory of my Nan in October, hopefully with continued weight loss and a gradual increase in training I will be able to run this and finish physical pain free.

On the more personal side of life it is hard to believe that in under 2 months my daughter will be 2 years old. Of course I am biased but everyone says what a happy, clever and well behaved girl she is. To us she is amazing and she clearly loves music, dance, sport (watching on TV and me playing badminton) and of course in the Night Garden is a huge hit. I don’t know if knowledge that these is a genetic element helps to drive me to look into this or not but I do know that I don’t want anyone to have to experience what I did with this condition let alone my daughter (something I don’t even want to think about).

As always feel free to contact me about anything relating to these conditions, although the blog is not getting updated as often as I would like I am still here, the patients series will be going still although it looks like I might just update it once a quarter or when I have the time.