London Friday 27th April 2012

Progress in the Search for Improved Diagnosis, Management and Treatment

Chairman: Dr F Anthony Greco

Topics

• Management and treatment approaches for CUP – a global perspective
• Implementing NICE guidance in a general hospital
• Targeting treatment to patients with specific mutational profiles
• Latest international research findings
• The Search for Improved Diagnosis using Molecular Profiling
• Exploiting underlying biological factors of highly metastatic cancers to develop more rational treatments
• Improving the Patient experience

After the success of the first international conference held in 2009, there is to be a new conference this year in 2012. CUP has remained for a long time, a hidden and little understood sub group of cancers with a generally poor prognosis. The first CUP conference helped to flesh out some of the commonalities of this sub group together with bringing news on new trials and approaches based on such techniques as molecular profiling. Since the last conference the NICE guidelines for CUP have been published in the UK.

For full information click here

The current site makes use of some static pages but most of the content for the near future is likely to be in the form of articles. Hopefully, anyone using the site will not get confused over the two different approaches, pages and categorised articles, being used at the same time.

The original site used to look like this: -

The WordPress theme comes courtesy of Michael Hutagalung’s Arthemia Free but with a few tweaks to make it look a little more like his Arthermia Premium version.
His theme is designed to give a magazine style to the WordPress platform.

Maybe we’ll have a try at making it look a bit more original at some point but for now providing more content is the priority.

References

Image is of Mr. Testicle

Please feel free to add suggestions as to other useful ideas or possible links.

Matt’s first pathology result included the following: -
“Microscopic Report
Viable tumour cells are seen which in places form pseudo-rosettes around vessels and are characterised by an anaplastic rhabdoid morphology with abundant refractile intracytoplasmic globules. Many of the cells show multinucleation and many also show very prominent amphophillic nucleoli. Small numbers of mature lymphocytes are scattered throughout the tumour, although this does not necessarily imply an origin from a lymph node …
… Vimentin is generally negative …
… These appearances are those of an undifferentiated malignant tumour with a rhabdoid phenotype …”

This was referred on for a second opinion which included the following: -
“Microscopic Description
A poorly differentiated round cell lesion composed by round polymorphic cells arranged in a solid pattern with geographic-type necrosis and numerous mitoses. The cells have a vesicular nuclei with large easinophilic nucleoli and a rhabdoid cytoplasm. The neoplastic cells strongly and diffusely express CD99, broad spectrum cytokeratins (MNF116) and low-molecular weight cytokeratins Cam 5.2 with a membranous and cytoplasmic stain. The other antibodies tested (CD34, vimentin, actin, desmin, Myf4, S100 protein and lymphoma markers) are negative.

Histopathological Opinion
A metastatic high-grade poorly differentiated round cell tumour with rhabdoid features expressing pan-cytokeratins. …”

Malignant Rhabdoid Tumours

Malignant Rhabdoid Tumours were first described as rare tumours of the kidney occuring in children of less than two years of age. The term ‘rhabdoid’ refers to the similarity in appearance under the microscope with cells found in Rhabdomyosarcoma. Subsequently, similar appearing tumours, were found in areas other than the kidney such as the central nervous system so the term ‘extrarenal’ was added.

Composite Extrarenal Rhabdoid Tumours

Later still cells with a rhabdoid appearance were found admixed with other cancer cells in a range of cancers in people of all ages. The ‘extrarenal’ tag is really superfluous and could be dropped. [2]

An unscientific search through the first 5 pages of results returned by Google with the phrase ‘Extrarenal Rhaboid Tumour’ found: -

So there is the strange situation where a whole variety of different tumours including some of unknown origin morph into cells with an appearance similar to those from a cancer occuring almost exclusively in childhood. They are also noted for being aggressive tumours.

Treatment

Having gone through all of the above, there is no real impact on the treatment where the recommendations when given are the same as for the primary tumour. In the case of unknown primary, the treatment would be as for unknown primary.

References

[1] Wikipedia Cell Culture
[2]INI1 expression and Composite Rhabdoid Tumours

I’m guessing that for the most part the consultant’s words were the ‘be all and end all’ of finding information. Digging around in medical libraries would have been time consuming and frustating without prior experience in this area. Digging around in a general library would have offered very little.

Now, however, the first step for many after the visit to the consultant, will be to open Google and see what the web has to say about a particular cancer or treatment regime.

Google Advanced Search

If you’re not already familiar with all the tips and tools available to help with finding information it can be worth 15 minutes reading up on the ‘Advanced Search Tips’ page on Google. The ability to use synonyms with ‘OR’ to improve the number of hits, or phrases “enclosed in double quotes” to narrow things down and there again the ‘-’ minus sign to -exclude -words can sometimes be of great help.

Alternative Search Engines

Trying other Search Engines may be worthwhile. Alta Vista for instance includes the ability to include dates in your search making it easier to exclude older information. Dogpile will search several other search engines in one hit and can be worth a trry.

Scientific or Scholarly Seaching

If you do have a more scientific background and want to look for more scholarly articles then Google helpfully provides its Scholar Search. The whole area of improving searches for the scientific community is benefiting from new approaches. You could take a look at the Vadlo and NextBio search engines. For any searches relating to cancer you will almost certainly get lots of hits from that massive database of information known as PubMed which I’ve just discovered has it’s own specialised search engine – GoPubMed which looks interesting but is new to me too!

Taking Notes – try Opera

If you want to take notes while keeping track of links and to have the ability to sort the notes into folders then give the speedy Opera a try. I find the Speed Dial really useful as well – a bit like the bookmark page in Chrome but more controllable.

A reminder – just take care not to get diverted from the original point of the search!!

Given that we replicate 6 billion cells per hour, serious perfection is needed to avoid errors [TBC].[3]

Of course with perfection in the biological world, evolution wouldn’t have occurred and we wouldn’t be here in the first place but then only mutations in germ cells can lead to evolution. Mutations occurring in regular cells are always disadvantageous.

Given the complexity of cell reproduction and the likelihood that mutations will occur, it is good to know that we have genes that can detect mutations and either repair them or can program a cell to commit suicide. The problem is that these detection mechanisms are also contained in the genes in the DNA so if these particular genes are mutated, cells can be formed without this protective mechanism.

References

[1]Human Genome Project
[2] Wiki on DNA Replication – and source of image
[3] Mens Health – Cancer Fighting Foods

The site is starting with the experience of one person and his family and friends but it is hoped that it will evolve to have a much wider relevance and scope over time.

When you are dealing with something as serious and as potentially fatal as cancer, you want to be sure that everything possible is being done and being done in a timely fashion.

The delays and uncertainties that arise when the experts are in the dark because it can’t be determined where the cancer started or the cancer is too rare to have much information, can sometimes lead to a lack of trust in the treatment being offered and anxieties about missed opportunities.

Ideally you will want to find someone with very similar problems who has received the right treatment to achieve complete remission and ultimately to be regarded as cured. However many of these people will be keen to get on with their lives after the scary period of living with cancer and who could blame them?

Those of us who supported someone for who we cared deeply and someone who ultimately lost their lives to cancer can still provide useful information and support. You may also benefit from knowing what we might now have done differently if we had sufficient knowledge from the start.

Matt and his family and friends were inspired by those personal websites that were willing to share some of the highs and lows experienced along the way as well as detailed information about the treatements and care given. Now when we think of Matt we want to give something back and we have been aided considerably by generous donations from the company he worked for.