Neuroendocrine Cancer – the devil is in the detail

Nick Robinson BBC
Nick Robinson BBC

Nick Robinson, well-known and ex-BBC Political Editor starts his new job today (16 Nov 15) on BBC Radio 4. He was until earlier this year, the most recognised political reporter face on UK TV, frequently stood outside 10 Downing St reporting on anything politics and at any time of the day.

Like a lot of people, Nick’s life changed when he was diagnosed with Cancer in Feb 2015. A self-confessed workaholic, he is now hoping to live a more balanced life after surviving lung cancer according to an article in the Sunday Times this weekend.

He assumes the post vacated by James Naughtie, an extremely hard act to follow – a man who would frequently sink his teeth into a politician’s leg and not let go until he got an answer – or at the very least he would paint them into an embarrassing corner. It’s a tough job as most politicians are extremely wily characters, masters of ‘double speak‘ and expert in answering a question without getting into the detail the questioner wants.  As we all know, the devil is in the detail.

Although the article introduces some new facts about his cancer experience, I was really looking for more detail.  That said, even without the ‘devil’, the latest article is inspiring for most (….man goes back to work after a tough fight with Cancer).

So why am I so interested in the detail of Nick’s Cancer? Simple – because he does not have Lung Cancer as frequently and widely reported in the media. Lung Cancer is the ‘politician’s answer‘ or the ‘double speak answer’ to avoid going into complicated detail. The correct answer is he has Neuroendocrine Cancer with a Lung Primary.

I’d really like to turn the tables and interview Nick, we seem to have so much in common. We are both self-confessed workaholics, we both went to an annual Asthma clinic, we both told our Asthma nurses we had lost weight and we both were sent for a scan as a result. Following our scans, we were both diagnosed with Neuroendocrine Cancer.  Like Nick, I also have an interest in politics but wouldn’t make a good one due to my love of detail and hate of ‘double speak‘.

This is not a new problem for Neuroendocrine Cancer.  The most famous of patients is the Apple founder and now deceased Steve Jobs.  He is frequently (even to this day) reported to have had Pancreatic Cancer rather than Neuroendocrine Cancer of the Pancreas (an Insulinoma to be precise).  Although not as famous as Jobs, UK musician Wilko Johnson (of Dr Feelgood fame) is a similar story. I touched on this dilemma in my article The Human Anatomy of Neuroendocrine Cancer.

Nick – good luck with the new job.  By the way, it’s really OK to say you have Neuroendocrine Cancer!

 

You can read the full article here if you have a Times subscription.

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

Neuroendocrine Cancer – don’t break my heart!

dont break my heart

NEW – 2017 guidance issued.  Diagnosing and Managing Hedinger Syndrome (Carcinoid Heart Disease) in Patients With Neuroendocrine Tumors – An Expert Statement published in the Journal of the American College of Cardiology.

The following are key points to remember from this Expert Statement about the diagnosis and management of carcinoid heart disease in patients with neuroendocrine tumors:

  1. Carcinoid heart disease is a frequent occurrence in patients with carcinoid syndrome and is accountable for substantial morbidity and mortality.
  2. The pathophysiology of carcinoid heart disease is not well understood; however, chronic exposure to excessive circulating serotonin is considered one of the most important contributing factors.
  3. N-terminal pro–B-type natriuretic peptide (NT-proBNP) appears to be the best biomarker to date for screening carcinoid syndrome patients for evidence of clinically significant carcinoid heart disease (Evidence Level 2-3, Grade B).
  4. Measurement of either 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA) or plasma 5-HIAA is mandatory for diagnosis and follow-up of carcinoid syndrome. Furthermore, a 24-hour urinary 5-HIAA level >300 μmol/24 hour is a useful marker for identifying those at risk of developing carcinoid heart disease (Evidence Level 2, Grade B).
  5. Transthoracic echocardiography remains the gold standard for diagnosis and follow-up of carcinoid heart disease. It should be performed in all patients with carcinoid syndrome and high suspicion of carcinoid heart disease, such as clinical features or raised NT-proBNP and/or 5-HIAA levels. For established carcinoid heart disease, echocardiography should be performed if dictated by a change in clinical status; otherwise/thereafter every 3-6 months, depending on the severity of established carcinoid heart disease and clinical status (Evidence Level 2, Grade B).
  6. Cardiac magnetic resonance can be used to evaluate the pulmonary valve, identify cardiac metastases, and assess right ventricular size and function (Evidence Level 2, Grade B).
  7. Long-acting formulations of somatostatin analogs are the standard treatment used to alleviate symptoms related to the carcinoid syndrome, and prevent the development and/or progression of carcinoid heart disease (Evidence Level 2, Grade B).
  8. In cases of carcinoid syndrome that are refractory to somatostatin analogs, options include escalation of the somatostatin analog dose to above labeled doses, addition of IFN-alfa, or peptide receptor radionuclide therapy (PRRT). The oral serotonin synthesis inhibitor, telotristat, represents a promising agent to improve symptoms of the carcinoid syndrome; however, it is not yet approved, and is currently only available for compassionate use in the United States. Given the limited data, everolimus cannot currently be recommended for the treatment of carcinoid syndrome (Evidence Level 2-4, Grade B/C). (NOTE: Since publication, PRRT now widely approved).
  9. The patient with carcinoid heart disease should be managed by a specialized multidisciplinary team, within a setting of a specialized neuroendocrine tumor (NET) center (Evidence Level 5, Grade D).
  10. An experienced medical (cardiologists and NET specialists with involvement of other specialists as necessary), surgical, and anesthetic team approach to the patient with carcinoid heart disease is critical to provide state-of-the-art management for these patients (Evidence Level 5, Grade D).
  11. The choice of valve prosthesis should be individually tailored on the basis of the patient’s bleeding risk, and possible future therapeutic interventions. Biological valve prostheses are the preferred option (Evidence Level 4, Grade D).
  12. To prevent a carcinoid crisis during surgery, the patient should be started on an IV octreotide infusion at a rate of 50-100 mcg/h at least 12 hours preoperatively; this should be continued throughout the procedure and until stable. Patients should be monitored for occurrence of bradycardia if high doses of octreotide are used (Evidence Level 4, Grade C).
  13. Patients with confirmed carcinoid heart disease should be referred to a NET center with cardiology and cardiac surgery departments having expertise in dealing with this complex pathology (Evidence Level 5, Grade D).

chd treatment

A useful abstract of Carcinoid Heart Disease information written by a patient for patients is below.

Neuroendocrine Cancer has certain unique features whereby tumours can produce one or more symptoms which are known collectively as a syndrome.  Neuroendocrine Tumours secreting excess amounts of serotonin, can be accompanied by Carcinoid Syndrome which if not diagnosed and treated early enough, can lead to an additional complication known as Carcinoid Heart Disease (CHD) or Hedlinger Syndrome. However, very late diagnoses can present with CHD already in place.

Excess serotonin, a hormone released by NETs into the bloodstream seems to be the prime and lead suspect for causing thick ‘plaques’ or fibrosis tissue within the heart muscle and damage to (mainly) the tricuspid and pulmonary valves on the right side of the heart which can become ‘tightly narrowed’ or ‘leaky’.  Other substances associated with Carcinoid Syndrome may also be involved (e.g. tackykinins). The presence of liver metastases may allow large quantities of these substances to reach the right side of the heart without being filtered out by the liver but the primary and other secondaries can still contribute to the problem. It’s important to note that the damage is nearly always caused by excess secretions of substances from malignant neuroendocrine cells rather than any direct metastatic involvement of the heart.

Patients with carcinoid heart disease normally present with symptoms such as breathlessness (dyspnea), fatigue, ascites, swollen ankles (edema). However some patients can be asymptomatic.  The left side of the heart is relatively protected, with the pulmonary circulation filtering out the majority of the serotonin and other substances produced by the tumours.  However, involvement of the left-sided valves can sometimes be seen in patients with very active metastatic disease, bronchial carcinoid or those with an existing heart condition known as Patent Foramen Ovale (hole in the heart).

When I was diagnosed in 2010, I was displaying symptoms of carcinoid syndrome and had to undergo a plethora of tests including something called an Echocardiogram – a sonogram (ultrasound) of the heart. Note – it is NOT abbreviated as ECG, which lay persons often use as an abbreviation for an Electrocardiogram – a totally different test.  Carcinoid heart disease is a relatively late manifestation of neuroendocrine tumours; however, it can have an impact on the prognosis of these patients. Thus, early testing is vital for each patient presenting with carcinoid syndrome so that treatment can be considered. Whilst there are certain biomarkers which might indicate the potential for Carcinoid Heart Disease to be present, Echocardiography is the gold standard for detection. Depending on the results of the Echocardiogram, two further investigatory tests may be ordered up – transoesophageal echocardiogram and cardiac catheterisation.  Patients without symptoms can undertake a blood test called NT-proBNP which can function as a screening test.

If you ‘google’ Carcinoid Heart Disease, be careful where you look as there are some statistics to be found in terms of incidence and prognosis.  I suspect they may be out of date and have yet to catch up with improvements in the latest diagnostic and treatment techniques. Either that or they fail to mention the disease might only be clinically significant in much smaller percentages.

On a positive note, I sense major strides in worldwide awareness campaigns which should lead to earlier diagnosis and therefore earlier treatment for Neuroendocrine Cancer. Combine that with new and innovative treatments in debulking/removing/shrinking tumours and controlling syndromes – particularly the use of somatostatin analogues with the latter, should mean that fewer people will succumb to this additional complication. I don’t see a lot of Carcinoid Heart Disease posts on the various forums which hopefully is a good sign.

I did blog about a new treatment for Carcinoid Syndrome called  XERMELO (Telotristat Ethyl) read here.  At ENETS 2016, a report claimed that it appeared to ‘halt Carcinoid Heart Disease’ or certainly reduce the risk.  Reducing the risk sounds feasible as Telotristat Ethyl reduces the ability to manufacture serotonin to levels which appear subthreshold to that which stimulates fibrosis associated with CHD. This drug might prevent the need for valve surgery in many cases, and enable the use of bioprosthetic valves in others, without recurrent fibrosis.  You can read the ENETS poster here.

Although I’m fairly stable, I still try to get an Echocardiogram on an annual basis and am very happy to have this one in my ‘test golfbag’. The procedure is painless and takes around 20-30 minutes.  My results have always been OK.  Information on the guidelines for CHD have been a bit sparse but a new paper published has proposed an ‘Algorithm for the Screening and Investigation of CHD.

Proposed Algorithm for the Screening and Investigation of CHD This graphic provides an algorithm for how patients with metastatic (serotonin-producing) neuroendocrine tumors (NETs) should be screened and assessed for carcinoid heart disease (CHD), including, importantly, when to refer to cardiology. f/u = follow-up; NT-proBNP = N-terminal pro–B-type natriuretic peptide.

If you have time please check out this excellent video presentation on Carcinoid and Your Heart with cardiologist Dr. Jerome Zacks from Mount Sinai Hospital and the Carcinoid Heart Center, both in New York City.

Please also note that fibrosis due to excess serotonin (and other substances) can also induce fibrosis in the mesentery, retroperitoneum, pleural and pulmonary cavity and the skin. This is fully covered in my article Neuroendocrine Cancer: Fibrosis – an unsolved mystery?

The Human Anatomy of Neuroendocrine Cancer

The Human Anatomy of Neuroendocrine Cancer

OPINION.  Sometimes when I’m searching for cancer information, I’m presented with a ‘pick-list’ of types which mostly tend to be anatomy based.  I do find it annoying when I cannot find my own cancer on the list …..some respectable organisations are just not as up to date as they should be!  I can now totally understand why so many Neuroendocrine Tumour (NET) patients have become their own advocates and why they have to shout quite loud for recognition and understanding.

One of the key facets of NETs is that it is not tied to a particular part of the human anatomy. Unlike (say) lung cancer, where the primary is in the lung, or breast cancer where the primary can be found in the breast, neuroendocrine tumours arise from a cell type which can be present more or less anywhere in the body.  Ignorance of this fact can at best lead to misinformation and confusion about Neuroendocrine Cancer – at worst, misdiagnosis and unnecessary treatment for something else (including a different type of cancer in the same location – see below for an example). Take my own diagnosis phase. When I look at the radiology reports produced prior to diagnosis, there were mentions of ‘peri-aortic lymphadenopathy’, ‘mass in the small bowel mesentery’, ‘multiple liver lesions’, ‘retro-peritoneal fibrosis’, ‘extensive lymphadenopathy consistent with lymphoma or metastatic adenocarcinoma’. You can see from the mostly generalised wording, there was some scope for confusion given that 3 potential cancers were mentioned in one paragraph.  However the biopsy confirmed NETs.  That is what is now documented, that is what I tell people I have and that is what I’m treated for.

The point I’m making here is that certain cancers can appear almost anywhere in the bodyNeuroendocrine Cancer is one of those. For example, a Neuroendocrine Tumour which originates in the intestines isn’t Bowel or Colon cancer. Similarly one which originates in the (say) Pancreas or Lung should not be confused with ‘core’ Pancreatic or Lung cancers. These are all histopathologically different cancers to NETs, they arise from different cells and the presentation, testing, treatment (curative or palliative) and prognosis can be very different.  At worst, the wrong treatment will shorten the patients life.  This is another key point as Neuroendocrine Cancers really need NET specialist medical teams (although there are certain types which I suspect on occasion may require external experts in conjunction with NET specialists).

A Neuroendocrine Tumour is NOT

Take the quite recent case in the news about Wilko Johnson, a well known R&B musician who was told he had Pancreatic Cancer and would die within 10 months.  But a friend (a doctor) became curious as to why he wasn’t dead after 10 months and why he wasn’t even feeling ill!  It was then discovered he had a NET, i.e. he had a Neuroendocrine rather than exocrine based cancer of the pancreas. So he went from dying to living (albeit living with the consequences of the cancer). Of course the newspapers even today continue to report he has “Pancreatic Cancer”.  Read his amazing story by clicking here.

And then there is the famous Nick Robinson BBC political reporter who is frequently reported to have “Lung Cancer” when in actual fact he has Neuroendocrine Cancer with a Lung primary.  Read his story by clicking here.

Dave Thomas the founder of Wendy’s Hamburger Chain had a Neuroendocrine Tumour but many newspaper reports said he died of liver cancer. Whilst they got the detail of the cancer correct, the ‘headline’ location is technically wrong as the liver was a metastasis (a secondary location). This robs us of vital awareness messages due to the ‘headline reading only population’.

They are not alone, the most famous NET patient is the late Steve Jobs (the founder of Apple).  To this day, it is frequently reported he had “Pancreatic Cancer” when in fact he had a Neuroendocrine Cancer with a primary in the Pancreas.  I see this error repeated weekly in my news alerts plus with many other diagnosed patients.  Read a very details Steve Jobs story by clicking here.

However, on 16th August 2018, some might say a person more famous than Jobs was diagnosed with Neuroendocrine Tumors (pancreatic primary). Aretha Franklin was initially diagnosed in 2010, other than pancreatic primary, other details are scant as she wanted to keep her condition private.  However, the media exploded with claims she died of Pancreatic Cancer, although several outlets did mention it was the ‘Neuroendocrine type’ and many left that bit out.  Although this left a little door open for Neuroendocrine awareness, the community faces a very difficult task in regaining the high ground and it is looking like ‘Steve Jobs’ all over again as the news went viral.  That said, it appears her death certificate does confirm Neuroendocrine Cancer.  Read more by clicking here.

On 13 Jan 2017, it was announced that Siri Co-Founder Dag Kittlaus has Pancreatic Cancer. Although the detail said Pancreatic Neuroendocrine Tumor, it is still a misleading statement and once again, the headline reading population receive only the Pancreatic Cancer message.

There are huge differences between Pancreatic Cancer and Neuroendocrine Cancer with a pancreatic primary – click here to read more. 

pancreatic vs neuroendocrine

I’ve also lost count of the number of times I’ve read regional and national patient stories where the headlines mentioned various parts of the anatomy only to find it was a Neuroendocrine Tumour in the detail.  Frustratingly, many of these articles are also fundraising for the wrong type of cancer in addition to the misdirected awareness messages.

The most well-known Neuroendocrine Cancer patients are so famous, thousand of articles were written about them when they died and continue to this day. These articles are ingrained in the bowels of the web and in books – many people will use them as research to reference in their own articles.  This issue will continue for many years.  

The same thing is now happening with UK celebrities Nick Robinson and Wilko Johnson to a certain extent (although Neuroendocrine is starting to creep into their vocabulary).  I have in fact had an online chat with Wilko Johnson who said he would help with Neuroendocrine publicity (not yet seen though).  Check out the conversation here:

wilko-response
Let me add that this is not an attempt to bash Aretha Franklin, Steve Jobs, Nick Robinson, Wilko Johnson, Dag Kittlaus or any patient, or any patient advocate organisation who have been recipients of cash raised for a different cancer. I believe patients mostly only say what their doctors say to them in terms of cancer type.

The power of social media will help to dilute the incorrect publishing of celebrities with the wrong cancer types, a particularly disadvantage for Neuroendocrine Cancer.  The more stories and articles like this one, the more we can do to counter the onslaught of incorrect articles which are denying our cancer the publicity we deserve. The share button is below.