Over the years of my advocating, I’ve tried to explain Neuroendocrine Cancer to many people outside the community. Some ‘get it’ but many don’t. Most understand ‘Cancer’, they have real difficultly understanding ‘Neuroendocrine‘. Despite how hard I try, I can see that some of them just don’t get it!
One of the challenges of explaining Neuroendocrine Cancer is the sheer complexity and spectrum of types. It’s a heterogeneous grouping of cancers ranging from some quite indolent versions through to very aggressive versions similar to many dangerous adenocarcinomas. Unlike many of the more understood cancers, Neuroendocrine Cancer can literally appear anywhere in the body, adding to an already complex description, in addition to creating a disadvantage of awareness opportunities – basically many doctors and media organisations don’t ‘get it’ either!
Add in the symptoms caused by Neuroendocrine Tumours and their associated ‘Syndromes‘ and ‘Hormones‘, the external audience is now falling asleep or lost interest. Trying to explain why these diseases cannot be diagnosed earlier is also very complex. “How can it be so difficult” many of them ask.
If you have managed to keep their interest and get onto the subject of living with the disease, it gets even more mind-blowing. Non-stop surveillance, lifetime surveillance, permanent side effects of treatment. “No way” many of them remark. The problem is that many people have a really simple outlook on cancer; something goes wrong, you get diagnosed, you get treated, you either die or live. Simple isn’t it?
One group that normally ‘gets it’ is those who have currently got it, i.e. Neuroendocrine Cancer patients and their close families and supporters. They may not ‘get it’ before someone is diagnosed and they may still not ‘get it’ once someone is diagnosed, but they eventually will ‘get it’. I have many people who ‘get it’ in my private group and on my main campaign sites.
Despite the difficulties, I’ll continue talking to those who have not yet ‘got it’ hoping to make them understand the disease. I also intend to continue to help with the undiagnosed (some of these guys probably do ‘get it’ but just not yet formally ‘got it’). I also want to help those at and beyond diagnosis who despite having it, don’t yet quite ‘get it’.
No one gets it until they get it. It shouldn’t be that way.
It’s no secret that Neuroendocrine Cancer can be difficult to diagnose. Although earlier diagnosis is improving (as reported in the SEER database report issued in 2017), there is still a lot of ground to cover. It’s also no secret that certain cancers are difficult to diagnose (NETs is one) and there are a number of reasons why this happens, including but not limited to: – they grow silently, they often produce vague symptoms which can be mistaken for much more common illnesses, and their complexity is not fully understood.
I wanted to cover two different aspects of the problem of finding NETs. Firstly, in finding the primary tumour so that the type of NET can be properly established – this drives the best treatment regime. Secondly in finding all the tumours, as this establishes the correct and most detailed staging declaration – this drives treatment plans and surveillance regimes that need to be put into place.
Hunting Tumours – Primary vs Secondary
It’s really important to determine which tumours are primary and which are secondary (metastasis). There’s a number of ways to help work this out and knowledge of NETs epidemiology studies can help.
Specialist Knowledge – certain things are known about the behaviour of NETs
Specialists and in particular NET specialists will be aware of the vagaries of NETs in terms of what tumours are normally a primary and which are normally secondary and many of the pitfalls involved in working that out. Many NETs will have metastasized to the liver at diagnosis, so whilst it is not impossible to have a primary liver NET, the vast majority of liver tumours found will be secondary (metastases). NET Specialists are more likely to have the experience than generalists. They know that the varying metastatic potential depending on the primary site clearly indicates differing biology and genetics across sites and they know that NETs are indeed a heterogeneous group of tumours. The differences cannot be explained by whether the NET is situated in the foregut, midgut, or hindgut. For example, Appendiceal NET is known to be less prone to metastasis. This may be due to the high rate of incidental ﬁndings during appendectomies, or because the appendix is an immunological organ where malignant cells can therefore be expected to be frequently recognized by the immune system.
The majority of the digestive tract is drained by the portal venous system, explaining the dominance of liver metastases in this group of tumours. This also explains our ﬁnding that many nervous system and bone metastases originate from NETs in the lungs. Disseminated tumour cells may directly reach the systemic circulation from the lungs, whereas if originating from the midgut region, they need to ﬁrst pass both the liver and the lungs.
As an example of this heuristic knowledge, one Swedish study indicated that two-thirds of peritoneal metastases will be attributed to Small Intestine NETs (SI NETs). SI NETs and Pancreatic NETs (pNETs) are the most likely to metastasize. The least likely sites to metastasize are the Appendix and Rectum. The same study indicated that in addition to the common metastatic locations of lymph nodes and liver, Lung NETs are more likely to metastasize to the brain and bone than other types. I believe the findings from this study more or less correlates to other information I’ve had access to and also confirms the technical behaviour paragraph above.
There are many other clues open to those involved in diagnosing a NET:
Patient. Very often the patient plays a big part of determining where the primary and other tumours might be by carefully describing symptoms.
Incidental Finds. NETs are very often found incidentally during trips to the ER/A&E and also during tests for something else. This is particularly the case with Appendiceal NETs and might explain why the average age of a patient is significantly lower in this type of NET.
Blood tests and Hormone Markers. We are not yet in a position where these types of tests can diagnose (but we are moving in that direction). In the case of unknown primaries (CUP), sometimes test results can help to find where some of these cancers started. With NETs, symptomatic patients can often test to confirm an elevated hormone marker which may narrow it down to a specific organ or gland. Read more here.
Scans and Endoscopies. Most cancers of a certain size may show up on conventional scanning such as CT, MRI and Ultrasound. Nuclear scans are now playing a bigger part in finding tumours which betray their location through functional behaviour by lighting up or glowing on these imaging devices. Endoscopies (e.g. gastroscopies, colonoscopies, even gastro intestinal pill cameras can be used) can help but like scans are not foolproof). Generally with NETs, if you can see it, you can detect it. Read more here.
Hereditary Conditions. Around 5-10% of NETs are hereditary in nature, mostly involving the MEN group of syndromes. Many of those people will know they are at risk of developing NETs and their doctors should know the most common locations for primary tumours associated with each gene. So a declared or suspected hereditary syndrome is useful in finding primary tumours if they exist and are proving difficult to find.
Biopsies. “Tissue is the issue”. Pathology can very often give really strong clues as to the type of NET and therefore the likely location of a primary tumour, for example additional tests such as immunostains. Many biopsies will come from secondary cancer (metastases), mostly the liver. Despite all the potential diagnostic routes above, the place the cancer started is sometimes still not found and this may lead to atypical diagnostic/treatment plans and in certain cases this might even include exploratory biopsies via surgery (invasive/minimally invasive), perhaps combined with opportunistic tumour removal if found during the procedure.
Staging. Simple staging can be given if locations of metastases are known. For example in the case of Liver metastases, the stage is automatically Stage 4. However, the full staging definition relies on knowing distant metastases, loco-regional metastases and the full Tumour/Node/Metastases (TNM) definition (size, spread, etc) cannot be given without a primary. Read more here.
Cancers of Unknown Primary
Cancer is always named for the place where it started, called the primary site. Sometimes doctors can’t tell where a cancer may have started. When cancer is found in one or more places where it seems to have spread, but the site where it started is not known, it is called a cancer of unknown primary (CUP) or an occult primary cancer.
When you look at the ratio of all cancers, the figure for cancers of unknown primary (CUP) is quite startling. Depending on where you look the figure is around 2-10%. That doesn’t seem a lot but when you consider the amount of people diagnosed with cancer, the total figure must be staggering. Interestingly, Cancer Research UK say that 60% of CUP cases are in the over 75s. In another interesting Swedish study, doctors claimed that the rates of metastatic cases were higher with certain NETs than they were in their anatomical counterparts, reinforcing the dangerous and sneaky nature of NETs.
Despite quite advanced scanning and diagnostic testing currently in place, and the extensive knowledge of NET specialists, there can still be reasons for not being able to find the primary tumour:
The primary is just too small to be seen and is growing quite slow. Very small cancers might not cause symptoms or be seen on scans. This is a particularly relevant point with NETs.
The primary could be hidden in tissue in between different organs causing confusion about the actual primary location.
The body’s immune system killed the primary cancer. It’s also possible (but not common) that any secondary cancer (i.e. metastases) is still growing.
The tumour has become loose from its primary location and exited the body, e.g. from a wall of the bowel and excreted out in the stool.
The primary cancer was removed during surgery for another condition and doctors didn’t know cancer had formed. For example, a uterus with cancer may be removed during a hysterectomy to treat a serious infection.
I hope this is useful for many NET patients, particularly those who are looking for a diagnosis or looking for a primary tumour.
Neuroendocrine Cancer – at times, it can really be like looking for a needle in a haystack.
One of the key awareness messages for Neuroendocrine Cancer is the hormonal syndromes that can often accompany the diagnosis for many people. As it’s a difficult disease to diagnose, many people struggle with these syndromes for some time before formal diagnosis of Neuroendocrine Cancer. Some continue to struggle after.
The cancer can often be uncannily quiet, but the tumours can be ‘functional’ and over-secrete certain hormones to add or introduce symptoms which mimic many other diseases or conditions, such as Irritable Bowel Syndrome, Menopause, Heart disease and Asthma. In addition to common symptoms of flushing and diarrhea, others include generally feeling weak, fatigued, pain, agitated, anxious, dizzy, nauseous, acid reflux, skin irritation, anaemic, lose weight, gain weight, low blood sugar, high blood sugar, heart palpitations, headaches, sweating, high blood pressure. Its main trick is to prevent you from being correctly diagnosed and it’s pretty good at it. For those looking for a diagnosis, it can be very frightening.
One or more of the NET syndromes can be a weird concoction of strange, powerful or terrifying ingredients, designed to make you very ill; and doctors will be confused.
Certain types of Neuroendocrine Cancer were once referred to by the out of date term of ‘Carcinoid‘ – now correctly referred to as a NET prefixed by its anatomical primary location. For the time being, the term Carcinoid Syndrome associated with these types of NET persists and this is known to be capable of over secreting (amongst others) the vasoactive substance called serotonin. It is commonly thought that serotonin is the cause of the flushing, but this is only partially correct, the flushing also results from secretion of kallikrein, the enzyme that catalyzes a conversion to bradykinin, one of the most powerful vasodilators known. Other components of the carcinoid syndrome are diarrhea, probably caused by the increased serotonin, which greatly increases peristalsis, leaving less time for fluid absorption, a pellagra-like syndrome, probably caused by diversion of large amounts of tryptophan from synthesis of the vitamin B3 (Niacin), which is needed for NAD production (oxidized form of B3). It also causes fibrotic lesions of the endocardium, particularly on the right side of the heart resulting in insufficiency of the tricuspid valve and, less frequently, the pulmonary valve and, uncommonly, bronchoconstriction. Other fibrosis spells include mesenteric and retroperitoneal desmoplasia which have the potential to dangerously obstruct important vessels and cause general discomfort at best.
Carcinoid Syndrome is one of the most powerful and dangerous ‘witch’s brews’.
The classic carcinoid syndrome includes flushing (80%), diarrhea (70%), abdominal pain (40%), valvular heart disease (40% to 45% but reduced to 20% since the introduction of somatostatin analogues), telangiectasia (25%), wheezing (15%), and pellagra-like skin lesions (5%). Carcinoid syndrome, first described in 1954 by Thorson and co-workers, has the following features: malignant neuroendocrine tumour of the small intestine, normally with metastases to the liver, sometimes with valvular disease of the right side of the heart (pulmonary stenosis and tricuspid insufficiency without septal defects), peripheral vasomotor symptoms, bronchial constriction, and an unusual type of cyanosis. One year later, Dr. William Bean gave the following colorful description of carcinoid syndrome:
“This witch’s brew of unlikely signs and symptoms, intriguing to the most fastidious connoisseur of clinical esoterica—the skin underwent rapid and extreme changes resembling in clinical miniature the fecal phantasmagoria of the aurora borealis.”
Other witch’s brews include the group of NET syndromes associated with over-secretions of Insulin, Glucagon, Gastrin, Vasoactive Intestinal Peptide (VIP), Pancreatic Polypeptide (PP) and Somatostatin. Read more about these and other syndromes here.
One of the most scary witch’s brews is the group of symptoms associated with one of the most uncommon types of NET, the catecholamine and metanephrine (adrenaline and noradrenaline) secreting tumours known as Pheochromocytoma and Paraganglioma. These tumours are likely to cause a barrage of symptoms such as High blood pressure, Heavy sweating, Headache, Rapid heartbeat (tachycardia), Tremors, Paleness in the face (pallor) and Shortness of breath (dyspnea).
All of the above is a diagnostic nightmare for those who have the symptoms and remain undiagnosed– no fun for the doctors either – this why we need so much more awareness and education – it’s one of the key aims of all my social media sites. Another aim of my sites is to support those who are diagnosed as these symptoms can continue following diagnosis and treatment. Many NET patients need constant surveillance and follow-up, many for life.
This is a very spooky disease, it will slowly grow without you knowing, it will mess with your body and mind, and if left alone to plot its devious and destructive course, it will kill. Some are faster growing but they have the same traits – they just kill faster. Share this post and potentially save a life.
Neuroendocrine Cancer is one of a number of “difficult to diagnose” conditions. Many types of Neuroendocrine Cancer come with an associated syndrome and these syndromes can mimic everyday illnesses. In some cases, many people don’t feel ill while the tumours grow. Most types of this cancer are slow-growing but there are also aggressive versions. Although things appear to be improving in diagnostic terms, it can sometimes take years for someone to be finally diagnosed correctly and get treatment, albeit in some cases, too late for any hope of a curative scenario. It’s a very sneaky type of cancer and if left too long it can be life threatening – CLICK HERE to find out why.
The road to a diagnosis of Neuroendocrine Cancer is often not straight or easy to navigate. It’s not only a sneaky type of cancer but it’s also very complex. It’s a heterogeneous group of malignancies with a varied and confusing histology and nomenclature to match. As I said above, many people are asymptomatic for years whilst the tumor grows and some might say that it’s somewhat ‘lucky’ to have symptoms to help aid a diagnosis. Many find that a lack of knowledge of Neuroendocrine Cancer in primary care, doesn’t always produce results. Common misdiagnoses include (but not limited to), Irritable Bowel Syndrome (IBS) and other common digestive diseases, menopause, appendicitis, hypertension, gastritis, asthma. Neuroendocrine Cancer is much more likely to be diagnosed at secondary care if a referral for ‘something’ can be achieved.
……..cue internet searches (Dr Google)
I think the rise and the power of the internet and rise of social media applications is very much helping generate awareness and knowledge of Neuroendocrine Cancer and those looking for a diagnosis may find help in this way. I suspect this instant access to information has played its part in the diagnostic improvements I mentioned above. Take my own efforts for example, I’m a wee Scottish guy with a computer and I’m already accelerating towards a million blog views – there’s clearly a market for what I produce. In terms of those looking for a diagnosis, if only one gets an earlier diagnosis due to my site, I’ll be happy.
Unfortunately, the internet can often be a minefield and in many cases, can lead to quite unnecessary worry for those looking for a solution.
I’m contacted almost daily by the ‘undiagnosed’ who suspect they have Neuroendocrine Cancer, often because they appear to be displaying the symptoms of one of the associated syndromes. These are some of my most difficult questions. I’m always very wary of initially agreeing with their assumptions and logic, instead opting for straightforward detective work based on my knowledge of the different types of Neuroendocrine Cancer, knowledge of the best scans, tumour markers, hormone markers. And I always warn them that statistically, they are more likely to have a common condition than the less common Neuroendocrine Cancer.
Many have already had multiple doctor’s appointments and tests. If they have not yet had a scan, I encourage them to try to get one ‘by hook or by crook’. Despite what you read on patient forums and surveys, the vast majority of Neuroendocrine diagnoses will be triggered by a conventional imaging such as CT and/or MRI. If you can see it, you can detect it.
When I first chat with the ‘undiagnosed’, I find many of them are fairly knowledgeable about Neuroendocrine Cancer and other health conditions, again confirming the power of the internet and the savvy ‘internet patient’. This is fine if you look in the right places of course – for certain things there are more wrong places on the internet than right ones.
If I have time, I’m happy to chat with these people, some are very frustrated – in fact some are so frustrated that they just want a diagnosis of something even if that something is really bad. Some are not showing anything on any scan but in certain cases, it can be likened to finding a needle in a haystack.
What do you say to someone who is utterly convinced they have Neuroendocrine Cancer but CT/MRI/Octreoscan/Ga68 PET are all clear, Chromogranin A and 5HIAA are in range but they still say they have (say) diarrhea with its potential for literally thousands of differential diagnoses. It’s a tough gig.
My scan came back normal. That should be good news. But, if there is no tumor, how can I be suffering from all the symptoms of carcinoid syndrome? Is that diagnosis wrong? Are the urine and blood test results wrong? I’m awaiting a MRI scan to take another look to see if the doctor can find anything. I don’t know what they’ll find. I don’t want them to find anything. But I’m afraid of what will happen if they don’t.
I always let the undiagnosed know that Neuroendocrine Cancer patients are some of the most friendliest and helpful people you can meet, they will treat you as one of their own. There will be a number of diagnosed people online who have gone through what the undiagnosed are going through, so they will both sympathise and emphasise. But … this can often have the adverse effect of pushing them into believing they must have Neuroendocrine Cancer. This makes for interesting discussions given the number of people who automatically assume that ‘flushing’ or ‘diarrhea’ (as described by the undiagnosed) must be Neuroendocrine Cancer without any reference to the many differential diagnoses and the context of what that actually means in Neuroendocrine Cancer terms.
10 Questions to ask your doctor/specialist for those Diagnosed with Neuroendocrine Cancer (and where to find a specialist)
I once wrote an article for DIAGNOSED NET Patients suggesting 10 Questions to ask their doctor. So I wanted to take a step back in context, using the knowledge I now have, and put myself in the shoes of someone who thinks they may have Neuroendocrine Cancer but is not yet diagnosed.
Key questions to ask your doctor/specialist for those trying to confirm or discount Neuroendocrine Cancer
Dear undiagnosed people. I totally understand your fear. There’s nothing worse than being ill and not knowing what illness you have. I’ve therefore compiled a list of 3 key questions for you to ask – think of it as a tick list of things to ask your doctor to do or check . I have linked several background articles for you to prepare your case. However, I cannot promise your doctor will agree or take any action, in fact some might be annoyed about the lack of trust. However, doing your homework really helps, including diaries and other evidence.
I also wouldn’t say that a negative to all the questions will mean you definitely do not have Neuroendocrine Cancer but at least these questions might provide your doctor and yourself with some food for thought, perhaps leading to the diagnosis of ‘something’. The questions below assume that routine blood tests have been done, including Full Blood Count, Liver, Renal, Bone, Glucose.
Questions for the UNDIAGNOSED to ask their treating physician
“I think I might have a type of cancer known as Neuroendocrine Cancer or Neuroendocrine Tumours (NET) because <<< insert your own story>>>. Would you please consider the following tests and checks:”
1. Chromogranin A (CgA) is a marker which is quite sensitive for Neuroendocrine Tumours, essentially measuring tumour bulk potentially indicating the presence of Neuroendocrine Tumours. There can be other reasons for an elevated CgA figure, including the patient’s use of proton pump inhibitors (PPI) (see the article for an alterative test where this is the case). Read more here – Neuroendocrine Cancer – Tumour and Hormone Marker tests.
3. Scans. Most NETs can be seen on a CT scan although liver metastasis can often show more clearly on an MRI. There are also nuclear scan options to confirm conventional imaging findings. Some NETs may be accessible via endoscopy and ultrasounds can also give hints for further investigation. In some cases, nuclear scans will find things that conventional imaging cannot because radionuclides can normally pick up oversecreting tumours. Read more in my article “If you can see it, you can detect it”.
You can hear two NET specialists talking about the issues surrounding the diagnostics here.
This is an excellent and positive video based overview of where we are with the Management of NETs. This is a presentation from a NET Specialist (who some of you may know) presenting to a “GI Malignancies” conference. This is therefore not only awareness of NETs, it’s also some good education for non NET GI experts who may only know the very basics. Useful for patients too! I met Dr Strosberg in Barcelona (ENETS 2017) and thanked him for his presentational and scientific paper output which I often use in my articles.
The classification picture is good as it explains the different facets of NETs and how NETs are classified and categorised in a general way – not seen it done this way before. Slightly out of date as it does not adequately convey the possibility of a well differentiated high grade recently classified by the World Health Organisation – read more here.
Amazingly it is delivered without using the word ‘carcinoid’ other than in reference to syndrome, indicating it can be done and is something also being reflected in all my posts to ensure they are up to date with the latest nomenclature. It’s also a good example for GI doctors as this branch of medicine is often involved in NET diagnostics and surveillance.
Excellent update of all the trials which have introduced treatments in the last decade.
Great update and worth the 30 minutes it takes to watch – you can view it CLICK HERE.
Firstly, let me say that I have no intention of advising you how to lose or gain weight! Rather, I’d like to discuss what factors might be involved and why people with NETs might lose or gain weight either at diagnosis or after treatment. Clearly I can talk freely about my own experience and associated weight issues. If nothing else, it might help some in thinking about what is causing their own weight issues.
I wrote a patient story for an organisation over 3 years ago and it started with the words “Did you mean to lose weight”. Those were actually the words a nurse said to me after I nonchalantly told her I thought I’d lost some weight (….about half a stone). I answered the question with “no” and this response triggered a sequence of events that led to all the stories in all the posts in this blog (i.e. my diagnosis).
I annoyingly can’t remember at which point I started to lose the weight but I was initially reported to have Iron Deficiency Anemia due to a low hemoglobin result and my subsequent iron test (Serum Ferritin) was also low and out of normal range. This, combined with the weight loss, the GP was spot on by referring me to a clinic. The sequence of events during the referral led to a diagnosis of metastatic NETs (Small Intestine Primary). If I had been a betting man, I would have put money on my GP thinking “Colorectal Cancer”. So my adage “If your doctors don’t suspect something, they won’t detect anything” applies.
I can also tell you that I weigh myself most days at the same time using the same scales. Weight loss or gain needs to be recorded. Clearly 2 or 3 pounds is nothing to worry about, I found you could put on or lose that amount in a day, depending on time of weighing and food intake. I’m looking for downwards or upwards trends of 7lbs or more (3kg).
Why did I lose weight?
The drop from 12st to 11st was clearly something to do with the anemia symptom (the NETs). But after diagnosis, I had major surgery about 10 weeks later. When I left the hospital after my 19 day stay, I was a whole stone lighter (14 lbs or 6.3 kg). I guess 3 feet of intestine, the cecum, an ascending colon, a bit of a transverse colon together with an army of lymph nodes and other abdominal ‘gubbins’ actually weighs a few pounds.
However, add the gradual introduction of foods to alleviate pressure on the ‘new plumbing’, and this is also going to have an effect on weight. I remember my Oncologist after the surgery saying to use full fat milk – the context is lost in memory but I guess he was trying to help me put weight back on. I also vividly remember many of my clothes not fitting me after this surgery. In fact, since 2010, I’ve actually dropped 2 trouser sizes and one shirt/jumper size. I did spend a lot of time in the toilet over the coming months, so I guess that also had an impact! However, what I wasn’t aware of was the side effect of my surgery. I started to put on some weight in time for my next big surgery – a liver resection. The average adult liver weighs 1.5 kg so I lost another 1 kg in one day based on a 66% liver resection.
However, what was also going on was something that took me a while to figure out – malabsorption and vitamin/mineral deficiency. My new ‘plumbing’ wasn’t really as efficient as my old one, so the malabsorption. issues caused by a lack of terminal ileum was slowly starting to have an effect. The commencement of Lanreotide in Dec 2010 added to this complication. That knowledge led me to understand some of the more esoteric nutritional issues that can have a big effect on NET patients and actually lead to a host of side effects that might be confused with one of the several NET syndromes. What it also confirmed to me was that I could still eat foods I enjoy without worrying too much about the effect on my remnant tumours or the threat of a recurrence of my carcinoid syndrome, something I was experiencing prior to and after diagnosis.
Armed with the ‘consequences of NETs’ knowledge, I did eventually adjust my diet and my weight has now ‘flat-lined’ at around 10 st 7 lbs (give or take 1 or 2 lbs fluctuation). Amazingly, the same weight I was when I left hospital after major surgery, looking thin and gaunt and not very well at all! The difference to day is that I have adapted to my new weight and look fit and healthy.
I actually lost another half a stone (7 lbs or 3.5 kg) in 2014 whilst training for an 84 mile charity walk – many commented that I looked thin and gaunt despite being extremely fit from all the training. Perspectives. It took several months to put the weight back on but at least I knew what had caused the loss and then subsequent gain.
I don’t have any appetite issues although I try to avoid big meals due to a shorter gut, so I snack more. With the exception of the 4 months of intense training for the 84 mile hike, I cannot seem to lose or gain weight. As my current weight is bang in the middle of the BMI green zone (healthy), I’m content.
Why do NET patients lose weight?
That’s a tricky one but any authoritative resource will confirm fairly obvious things such as (but not limited to) loss of appetite and side effects of cancer treatments. NETs can be complex so I resorted to researching the ISI Book on NETs, a favourite resource of mine. I wanted to check out any specific mentions of weight and NETs whether at diagnosis or beyond. Here’s some of the things I found out:
Carcinoid Syndrome. Weight loss is listed but not as high a percentage as I thought – although it tends to be tied into those affected most with diarrhea.
Gastrinoma/Zollinger-Ellison Syndrome. Up to half of these patients will have weight loss at diagnosis.
Glucagonoma. 90% will have weight loss.
Pheochromocytoma. Weight loss is usual.
Somatostatinoma. Weight loss in one-third of pancreatic cases and one-fifth in intestinal cases.
VIPoma. Weight loss is usual.
MEN Syndromes. One of the presentational symptoms can be weight loss.
Secondary Effects of NETs.
Many NETs can result in diabetes (particularly certain pNETs) and as somatostatin analogues can inhibit insulin, it could push those at borderline levels into formal diabetic levels (including any type of NET using long term somatostatin analogues). In people with diabetes, insufficient insulin prevents the body from getting glucose from the blood into the body’s cells to use as energy. When this occurs, the body starts burning fat and muscle for energy, causing a reduction in overall body weight.
It must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above.
What about weight gain?
You always associate weight loss with cancer patients but there are some types of NETs and associated syndromes which might actually cause weight gain. Here’s what I found from ISI and other sources (as mentioned):
Cushing’s Syndrome. Centripetal weight gain is mentioned. (Centripetal – tends to the centre of the body). I also noted that Cushing’s Syndrome tends to be much more prevalent in females. Cushing’s syndrome comprises the signs and symptoms caused by excessive amounts of the hormone cortisol (hypercortisolism) or by an overdosage of drugs known as glucocorticoids.
Insulinoma. Weight gain occurs in around 40% of cases, because patients may eat frequently to avoid symptoms. However, according to an Insulinoma support group site, I did note that after treatment (some stability), things can improve.
Again, it must be emphasised that there will always be exceptions and the above will not apply to every single patient with one of the above. As in weight loss scenarios, the Secondary Effects of NETs can have an effect.Hypothyroidism is another potential issue and weight gain is a listed symptom. I just been diagnosed with hypothyroidism this year but I was not gaining weight!
The NETs Jigsaw
Like anything in NETs, things can get complex. So it is entirely possible that weight loss or weight gain is directly caused by NETs, can be caused by side effects/secondary effects of treatment, and it’s also possible that it could be something unrelated to NETs (Dr Liu “Even NET patients get regular illnesses“). I guess some people might have a good idea of the reason for theirs – my initial weight loss was without doubt caused by the cancer and the post diagnostic issues caused by the consequences of the cancer.
I guess that weight loss or weight gain can be a worry. I also suspect that people might be happy to lose or gain weight if they were under/over weight before diagnosis (every cloud etc). However, if you are progressively losing weight, I encourage you to seek advice soonest or ask to see a dietician (preferably one who understands NETs).
Edit: I changed my blood thinner in May 2017 and lost 2kg (4 pounds) after 6 months.
Edit: I started Creon at the beginning of 2018 (read about this here) and almost immediately put on 2kg (4 pounds) to offset the 2kg loss from 6 months prior. However, no real change after 3 months of Creon (March 2018).
Edit: I was recently diagnosed with Hypothyroidism, one of the symptoms can be weight gain. Clearly that has not applied to me. Hyperthyroidism is the opposite condition where weight loss is a symptom.
Edit: Due to a bad chest infection in June 2018 and due to the consequences of the effects of that illness and most likely the treatments undergone, I have dropped three quarters of a stone (~10lbs). My lightest weight for over 30 years. To me that is a significant loss of weight in such a short space of time. Currently trying to put it back on again – I need the weight!
Edit: 4 Sep 2018. After the 10lbs (~4.5kg) loss following the chest infection, people who see me regularly have noticed the visible difference. I’m still struggling to get back beyond 10st after 2 months. I’m monitoring this really closely.
Edit: 28 Nov 2018. I’m back at 10st after increasing my dosage of Creon.
Edit: 10 Jan 2019. I’m back at 10st 3lbs, my approximate weight before the chest infection. It’s taken 7 months and the recent acceleration coincides with Creon dose increase.
Edit 7th Feb 2019. Changed from Creon to Nutrizym.
Edit: 17 Mar 2019. It appears my trouser waist size is back to 32″. Is the use of Pancreatic Enzymes making me eat more, or getting more nutrients through, or making me eat food which makes me put on weight?
For those wishing to see the output from an online discussion with Tara Whyand on the subject of ‘Weight’ issues for NET patients – please see this link inside my closed Facebook group.
In my article ‘Ever wonder what caused your NET’, I concluded that currently, the only known scientifically explained causes for NETs were hereditary/genetic in nature. This is mostly associated with those who have MEN syndromes (yes, they are a syndrome not a type of tumour) and a few other less common types of NET including Pheochomocytoma/Paraganglioma (Pheo/Para) and Medullary Thyroid Carcinoma (MTC) (the familial version of MTC is often referred to as FMTC). However, please note this does not mean that all those diagnosed with pancreatic, parathyroid, pituarity, Pheo/Para and MTC tumours, will have any hereditary or genetic conditions, many will simply be sporadic tumors.
In recent years, it has become increasingly apparent that a number of Neuroendocrine tumours arise as a result of germline genetic mutations and are inherited in an autosomal dominant pattern. The number of genes implicated is increasing.
Apparently, 5-10% of Gastroenteropancreatic NETs (GEP NETs) are estimated to have a hereditary background. Syndromes associated with these include Multiple Endocrine Neoplasia (MEN), Von Hippel Lindau (VHL), Neurofibromatosis Type 1 (NF1), Tuberous Sclerosis (TS) and others. People who have a genetic condition may present with the tumors (perhaps along with an associated syndrome) and so the genetic condition if there is one, may not be known at this point.
How will I know if I am affected?
Some people do worry about this, often because of what they find on the internet including inside patient forums. I suspect some people already know via family connections and I guess if you have 2 tumors found in (say) parathyroid and pancreas, it should at least raise a suspicion for MEN1.
Many people say how do I know, how do I check and this is obviously a delicate subject. Of course, your first port of call should be your NET specialist if you suspect or know of any connection.
Thus why I was interested in a paper published in Springer Link – titled “When should genetic testing be performed in patients with neuroendocrine tumours.” When reading, you’ll find it’s actually much more than that! Check it out here:
When should genetic testing be performed in patients with neuroendocrine tumours?
In this review, the authors examined the features which may lead a clinician to suspect that a patient may have an inherited cause of a NET and they outlined which underlying conditions should be suspected. They also discussed what type of screening may be appropriate in a variety of situations. If there is a way to identify which patients are likely to have a germline mutation, this would enable clinicians to counsel patients adequately about their future disease risk, and allows for earlier detection of at-risk patients through family screening. There’s a couple of minor errors in the text but I’ve contacted the authors.
The authors focused on presentations of NETs of the gastrointestinal system, chromaffin cell tumours (Pheochromocytoma and Paraganglioma) and Medullary Thyroid Carcinoma. Pituitary tumors (normally associated with MEN1), were not considered in scope for the review. Interesting, the review includes news of a move by endocrinologists to reclassify ‘Pituitary Adenomas’ as Pituitary NETs (PitNETs). Read the abstract here. This would appear to be in line with a gradual shift from the benign nomenclature associated with certain NETs to the ‘malignant’ potential of these type of tumors. The abbreviation is also in line with others, e.g. pNET, SiNET, etc. A useful reminder that we must stop using the term ‘Carcinoid‘ as this is regressing this extremely useful initiative to highlight the malignant potential of all NETs.
There also appears to be some linkage to the study looking at the possibility of familial Small Intestine NETs (SiNETs). You can read more about a US registered trial here (with apologies for use of the now defunct term ‘Carcinoid‘).
This is a complex subject and the text above is very basic. If you wish to dig further, the quoted reference is a good read. Just to emphasise, it’s aim is to provide advice about when to recommend genetic testing for NETs, and in doing so provides some useful reference information. It’s broken down into 4 distinct tumor groupings:
Since my diagnosis of incurable and metastatic neuroendocrine cancer in 2010, it’s really all been about me. I didn’t see the trauma coming, and my family has supported me throughout every single step. I really don’t want to be the focus of attention as that mantle was normally evenly distributed. However, there’s nothing like a cancer diagnosis to put you into the spotlight.
Facing an uncertain future with regular scans, injections, treatment, pills, examinations and blood tests has made me the center of attention, whether I like it or not. The focus is on me because these things are necessary to keep me alive for as long as possible and also because I live with the consequences of cancer and its treatment which provides further challenges. A good quality of life is not only a motivator for change, good planning and constant surveillance, but it’s also hard work and has an additional impact on the whole family. It means all activities including work, holidays, days out, social activities and, even the simple act of eating, might all need to be organized around me due to the vagaries of my condition. It will never stop, it will never end and it will always be about me!
This has gone on for seven years and counting. “Cancerversaries” are on the calendar alongside birthdays and wedding anniversaries. Tumor marker tests and scans are reviewed twice yearly so the relentless attention continues, often peaking at these test milestones and worrying moments in between. The detailed analysis of unusual pain or other disturbances are documented. The attention is on me.
Then, my wife finds a lump. The local doctor investigates and refers her for a mammogram. The mammogram check leads to an ultrasound which then leads to a biopsy of some fibrous tissue. We have a two-week wait before the all clear is given but the worry doesn’t immediately dissipate as another check was scheduled for three months (done, no issues). The following check 6 months after on 7 Aug 2018 is also no change. Hang on a minute … this is not about me!
I’m starting to realize it shouldn’t be all about me and it needn’t be all about me. It’s about other people, too. There is nothing in the rule book that allows cancer to be limited to a single family member. Cancer doesn’t really care how many in your household already have the disease – anyone is a target. It’s bad enough having one cancer patient in the house without another cropping up. One thing is for sure, when it comes to a cancer diagnosis in the family, I really want it to be all about me.
Postscript: Very excited to share my first article published in CURE magazine. This is a real story about recent events involving my own family. As a long-term cancer patient, it can seem like it’s always about ‘me’ and then something happens which changes that perception. It’s actually about others too, and always has been. If you want to talk about something similar in your life, please share with others in your comments below or message me.
This is the beginning of a new phase in my activities and another opportunity to spread awareness of Neuroendocrine Cancer to new audiences, something I promised I would do. I hope you will support my first contribution to an exciting organisation brand.
It would be great if you would take the time to read the article directly on the Cure site here, and any likes, comments and sharing would be appreciated.
I found some of the quotes from the recent NET SEER Database study (Dasari et al) very interesting. The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program is a comprehensive source of population-based information initiated in 1973 that is updated annually. Although the study is US-based, it represents the largest study of Neuroendocrine Tumors (NETs) ever recorded and is therefore a good guide to what might be found beyond USA. In fact, other national declarations of incidence and prevalence of NETs seem to bear these statistics out, i.e incidence rates of 7-8/100,000 …… almost 7 times the rate recorded in the 1970s. If you want to understand the factors behind this massive increase, I covered this extensively in my post “Neuroendocrine Tumors – not as rare as you think“. In this article, I looked at USA and beyond. Those who are regular readers of my articles will already know I’ve been ‘banging on’ about this for a few years. Other organisations and individuals (including NET specialists) are now indicating these tumors are not rare, some vindication for my aforementioned ‘banging on’. This is now a serious disease with some serious statistics behind it and we need a new way of doing things.
There are two further quotes which I’d like to focus on in this article:
1. From the NET SEER Database study published 2017:
” …… many cases of NETs may not have been reported to cancer registries unless considered malignant…… it is likely that we have underestimated their true incidence and prevalence” – i.e. the slide here:
2. From Dana Farber (Kulke, Chan):
“Estimated more than 200,000 undiagnosed cases in the US” – this slide here:
…. But what do these quotes actually mean? Here’s my take:
Underestimating the true incidence and prevalence of NETs
I studied the latest SEER NET study, formally titled “Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States” (authored by Arvind Dasari, MD, MS; Chan Shen, PhD; Daniel Halperin, MD; et al). From this document, I can see the authors were aware of the well-known faults in cancer registries worldwide and the effect this has on the true incidence and prevalence of Neuroendocrine Cancer. These issues, which are a worldwide problem, include the incorrect registration of Neuroendocrine Cancer as other types based on the anatomical location of the primary tumor. At this point, you may wish to check out my post “The Human Anatomy of Neuroendocrine Cancer” which provides some real life examples of the confusion between primary Neuroendocrine location and other cancers. That said, things are definitely improving because the latest SEER data shows a marked increase in the incidence of High Grade Neuroendocrine Carcinomas (NEC), an area where this issue is prevalent. A similar increase in NEC was also illustrated in the UK’s figures from Public Health England (PHE) in 2016 (click here) indicating that cancer registries are getting better and not before time, although it has to be said this only came about due to a major intervention by NET Patient Foundation and others. Through this work, it’s becoming clear that the incidence of all NETs in UK is around 8 to 9 per 100.000 (rare threshold <=5).
But there’s another issue impacting whether a diagnosis is actually entered on a cancer registry or not. Unfortunately, there are members of the medical community who still see well differentiated NETs as benign tumors, ‘not a proper cancer’ and still use ancient terminology ……… ‘Carcinoid’. The WHO 2010 classification for NETs was based on the concept that all NETs have malignant potential. Here’s a quote from the UKINETS Guidelines in 2011 (Ramage, Caplin, Meyer, Grossman, et al).
Tumours should be classified according to the WHO 2010 classification (Bosman FT, Carneiro F, Hruban RH, et al. WHO Classification of Tumours of the Digestive System. Lyon: IARC, 2010). This classification is fundamentally different from the WHO 2000 classification scheme, as it no longer combines stage related information with the two-tiered system of well and poorly differentiated NETs. The WHO 2010 classification is based on the concept that all NETs have malignant potential, and has therefore abandoned the division into benign and malignant NETs and tumours of uncertain malignant potential.
The guidance in WHO 2017 for Endocrine Organs reinforces this statement.
The undiagnosed NET patient population
From above, you can see why the incidence (and therefore the prevalence) of our disease has almost definitely been underestimated. However, that’s not the end of my story……..
A number of statements are clear about Neuroendocrine Tumors:
Low/Intermediate grade well differentiated tumors are known to have been growing slowly over a number of years before discovery or accurate diagnosis occurs,
They can be difficult to diagnose,
They are not that well-known amongst the general medical population,
Many people are initially misdiagnosed with another condition, with some this will result in late presentation with metastatic disease.
Many NETs are found during autopsies.
The living undiagnosed. It’s worth pointing out that one of the conclusions made by the recent SEER NET study is that the increase in incidence and prevalence can be attributed to a number of factors including earlier diagnosis. This is of course excellent news. Also worth noting that another conclusion of the study is that we are all living longer, reflecting improvements in therapies. This is also great news and is a factor in increased prevalence figures. However, it seems obvious that there are hundreds of thousands of people out there still be diagnosed who have tumors silently growing inside them and who are in a loop of referrals between primary and secondary care awaiting a proper diagnosis. See the Dana Farber slide above. Please help these people by sharing this article (you never know who it will reach – Diagnosing the Undiagnosed.
The dead undiagnosed? The true incidence of NETs may be much higher owing to the lack of diagnosis until after death. For example:
In USA, a respected NET specialist stated that the autopsy find for (excuse the outdated terminology…….) ‘carcinoid‘ is 4 times the recorded diagnosis rate (based on the known incidence rate at the time, this is 8 per 100,000).
In Australia, one study claimed that 0.05% of all autopsies found a Pheochromocytoma or Paraganglioma. “
The Mayo Clinic experience shows that in up to 50% of cases of pheochromocytoma, the correct diagnosis is made at autopsy (ergo the incidence rate could be double what is published).
Here is an article claiming that former US President Dwight D Eisenhower had a biopsy confirming he had a Pheochromocytoma. Click here.
A Hong Kong study indicated that 1% of all autopsies discovered an ‘Islet Cell’ tumour (i.e. a Pancreatic NET or pNET).
In one series, (excuse the outdated terminology…….) ‘carcinoid’ tumors were found in 1.22% of 16,294 autopsies in Malmö, Sweden, 90% of which were incidental findings.
It’s possible that many of these people showed no NET symptoms during their life but …… it’s equally possible that many of these people had NET symptoms but just put up with it and/or had been diagnosed with something else, and then died without a correct diagnosis. There is no evidence that any investigation follow ups were done so this possibility remains.
The potential for even more undiagnosed. To add to the underdiagnoses of NETs issue, is this most amazing piece of research published in 2018 – Pan-cancer molecular classes transcending tumor lineage across 32 cancer types, multiple data platforms, and over 10,000 cases. It was published in the American Association of Cancer Research (AACR) journal ‘Clinical Cancer Research and authored by Chad Creighton et al. DOI: 10.1158/1078-0432.CCR-17-3378. This was a pan-cancer piece of research which indicated that Neuroendocrine disease may be more prevalent than anyone has ever thought. There’s a summary article here which I suggest you read fully. The rather explosive extract is as follows:
I suspect there’s an invisible patient population for many conditions but the slow-growing and relatively quiet nature of Neuroendocrine Cancer means there could be a significant undiagnosed burden walking around, looking for a diagnosis, putting up with symptoms and being treated for other conditions. I see people on forums looking for clues, social media can sometimes be helpful here. That said, I do get the feeling some do not have NETs, regardless of the symptoms they associate with the disease, but I guess many of them will go on to be formally diagnosed with something. I’m contacted by many ‘undiagnosed’ people on my own blog and supporting Facebook sites (mostly privately) and I can tell you that’s a tough gig. I only hope I’ve given them some useful ideas about where to look or what to ask/suggest.
I feel earlier diagnosis reported in the SEER study is partly due to increased awareness, particularly in the medical world. I would also suggest that it has improved in the general population due to the explosion of social media information dissemination. It’s also accurate to say that improvements in diagnostic capabilities is also playing its part in pushing up incidence rates, just as improved therapies have pushed up prevalence rates, something emphasised by Dasari (et al) in the most recent study. Things are improving but there is so much more to do.
The issues caused by inefficient registries together with ‘the undiagnosed’, combine to suggest there is a large invisible NET patient population out there ……. we just need to find them!
Thanks to NET Patient Foundation for featuring this article here.
ASCO (American Society of Clinical Oncology) is one of the biggest cancer conferences in the world normally bringing together more than 30,000 oncology professionals from around the world to discuss state-of-the-art treatment modalities, new therapies, and ongoing controversies in the field. As Neuroendorine Tumors is on a roll in terms of new treatments and continued research, we appear to be well represented with over 20 ‘extracts’ submitted for review and display. This is fairly complex stuff but much of it will be familiar to many. I’ve filtered and extracted all the Neuroendocrine stuff into one list providing you with an easy to peruse table of contents, complete with relevant linkages if you need to read more. For many the extract title and conclusion will be sufficiently educational or at least prompt you to click the link to investigate further. Remember, these are extracts so do not contain all the details of the research or study. However, some are linked to bigger trials and linkages are shown where relevant. I’ve also linked to some of my blog posts to add context and detail.
I’m hoping to capture any presentations or other output from the meeting which appears to be relevant and this will follow after the meeting. I will also be actively tweeting any output from the live event (for many cancers, not just NETs).
There’s something for everyone here – I hope it’s useful.
Conclusions: Objective response to PRRT defines a subset of patients with markedly improved PFS. SUVave 21.6 defines a threshold below which patients have a poor response to PRRT. This threshold should be taken forward into prospective study.
Check out my recent blog discussing ‘Theranostic pairing” – click here
Conclusions: The duration of SSA use was positively associated with QoL benefit among CS patients. This may be explained by long-term effectiveness of SSAs or selection bias favoring patients with more indolent disease. Future studies will be needed to distinguish between these possibilities.
Conclusions: The incidence of weight gain was dose-related on TE and was greater than that on pbo. It was possibly related to a reduction in diarrhea severity, and it may be a relevant aspect of TE efficacy among patients with functioning metastatic NETs. Clinical trial information: NCT01677910
Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.
Conclusions: CAPTEM shows activity in neuroendocrine tumor of unknown primary. Currently FDA approved treatment options for grade I and grade II GI NETs includes somatostatin analogs and everolimus. Both of which are cytostatic and of limited use in case of visceral crisis or bulky disease where disease shrinkage is required. CAPTEM should be considered for grade II NETS of unknown primary.
Conclusions: This is the first multi-center study in Mexico. Which reflects the clinical characteristics of the NET_GET. The results differ in their epidemiology from that reported in other countries. However, the clinical and therapeutic results are very similar.
Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496
Conclusions: CLARINET OLE suggests sustained antitumor effects with LAN 120 mg in enteropancreatic NETs irrespective of tumor origin, and suggests benefits with LAN as early treatment. Clinical trial information: NCT00842348
Conclusions: Pts showed improvement in CS symptoms of flushing and diarrhea and reduction in 5HIAA levels with LAN treatment, indicating efficacy of LAN regardless of prior OCT use. Transition from OCT to LAN was well tolerated among prior OCT pts in ELECT. Clinical trial information: NCT00774930
Conclusions: These findings highlight the utility of molecular classification to identify distinct NET tumor types/subtypes to improve diagnostic precision and treatment decision-making. In addition, significant differences in the distribution of molecular diagnoses of NET subtype by age and gender were identified.
Conclusions: In this poor prognosis G3 NET cohort of whom 77% had received prior chemotherapy, a median OS of 18 months from start of PRRT is encouraging and warrants further study. PRRT is a promising treatment option for patients with G3 NET with high somatostatin-receptor expression selected by SSRI.
Conclusions: Occurrence of documented carcinoid crisis was low in this high-risk population. However, a significant proportion of patients developed hemodynamic instability, suggesting that carcinoid crisis is a spectrum diagnosis and may be clinically under-recognized. Use of octreotide was not associated with risk of carcinoid crisis or hemodynamic instability; however, this analysis was limited by our modest sample size at a single institution. There remains a need to establish an objective definition of carcinoid crisis and to inform standardization of periprocedural use of octreotide for at-risk patients.
Conclusions: By assessing patients with GI NET from two independent US claim databases, this study suggested that patients diagnosed with CS were 2-3 times more likely to be diagnosed with liver disorder, enlargement of lymph nodes, or abdominal mass, than those without CS during the one year prior to CS diagnosis. Future studies using patient medical charts are warranted to validate and interpret the findings. These findings, when validated, may aid physicians to diagnose CS patients earlier.
Conclusions: Radiological progression within 12 months of completion of PRRT is associated with a worse outcome in terms of OS. Patients with greater liver involvement and highest CgA levels are more likely to progress within 12 months of treatment completion. Earlier treatment with PRRT in patients with radiological progression not meeting RECIST criteria may need to be considered. There may be a greater survival benefit if PRRT is given prior to the development of large volume disease.
Conclusions: To the best of our knowledge, this is the first population-based study to examine potentially relevant pre-existing symptoms, resource utilization and healthcare costs before NET diagnosis. NET patients were more likely to have certain conditions and incurred higher resource utilizations and costs in the year preceding diagnosis of NET.
Conclusions: This population-based study showed that elderly NET pts have significantly different prevalence of co-morbidities compared to non-cancer controls. The impact of these conditions on survival and therapeutic decisions is being evaluated.
Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.
Role of 92 gene cancer classifier assay in neuroendocrine tumor of unknown primary. | 2017 ASCO Annual Meeting Abstracts
Conclusions: Tissue type ID was able to identify a primary site in NETs of unknown primary in majority (94.7%) of cases. The result had direct implication in management of patients with regards to FDA approved treatment options in 13/38 patients (pNETs, merkel cell and pheochromocytoma).
Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NET. The NETest accurately measures the effectiveness of treatment.
Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.
Check out my blog post on Gradingwhich has incorporated latest thinking in revised grade 3 classification
Seung Tae Kim
Theranostic trial of well differentiated neuroendocrine tumors (NETs) with somatostatin antagonists 68Ga-OPS202 and 177Lu-OPS201.
Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 68Ga-OPS202/177Lu-OPS201 as a theranostic combination for imaging and therapy. Additional studies are planned to determine an optimal therapeutic dose and schedule. Clinical trial information: NCT02609737
Conclusions: SREs in NEN patients with BM were not uncommon, especially in patients with grade 3 NEN and osteolytic metastases. Application of ART did not significantly alter median OS or TTSRE, no subgroup with a benefit of ART could be identified. The use of ART in NEN should be questioned and evaluated prospectively.
Conclusions: Rhenium Re 188 P2045, a radiolabeled somatostatin analog, may be used to both identify and treat lung cancer tumors. The ability to image and dose patients with the same targeted molecule enables a personalized medicine approach and this highly targeted patient therapy may significantly improve treatment of tumors that over express somatostatin receptor.
There’s a lot of inaccurate and out of date information out there. Some of it is propaganda but most is a combination of misunderstanding and patient forum myth spreading …….
Myth 1: All Neuroendocrine Tumours are benign
Not true. By any scientific definition, the word ‘tumour’ means ‘an abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumours may be benign (not cancerous), or malignant (cancerous)’. Sure, some NETs will be benign. However, The World Health Organisation (WHO) 2010 classification for digestive system is based on the concept that all NETs have malignant potential, and has therefore abandoned the division into benign and malignant NETs and tumours of uncertain malignant potential. This has been reinforced in the 2017 update to include clarification for other endocrine organ types of NET including Pheochromocytoma. Read more here. The word ‘Carcinoid’ is inextricably linked with this issue – read here why we need to stop using the term to help fight the benign myth.
Myth 2: Neuroendocrine Tumours is a terminal condition
Not true. By any definition of the word terminal in a medical diagnostic context, most NET patients have a good prognostic outlook, even those with metastatic and incurable variants of the disease. Read more here.
Myth 3: Carcinoid is another word for Neuroendocrine Tumours
Not true. Carcinoid is a very old term and was phased out years ago. Carcinoid is not mentioned in the latest WHO Classification schemes for Neuroendocrine Neoplasms (a term covering Neuroendocrine Tumours and Neuroendocrine Carcinoma). Unfortunately, the problem is exacerbated by organisations and individuals who still use the word. Also, those who use the following terms:
“Carcinoid and Neuroendocrine”,
“Neuroendocrine and Carcinoid”,
“Carcinoid NETs” or “CNET”
These are all contextually incorrect and misleading terms (not to mention the bad grammar). ENETS, NANETS and NCCN publications are gradually phasing the word out except in relation to Carcinoid Syndrome (and even then there could be easy solutions for this). Read more here and here.
Myth 4: All NET patients get ‘carcinoid syndrome’
Not true. Firstly, many NET cancers are non-functional; and secondly, carcinoid syndrome is only one of a number of “NET Syndromes” associated with the various types of NET. However, the issue is further confused by those who use the word ‘Carcinoid‘ to incorrectly refer to all NETs and use Carcinoid Syndrome to refer to all NET Syndromes. Read more here.
Not true. Steve Jobs had a Neuroendocrine Tumour of the Pancreas. Ditto for a few other famous names. Read more here.
Myth 7: I’m not getting chemotherapy, I must be doing OK?
Not true. For some cancers or some sub-types of cancers, although it remains an option, chemotherapy is not particularly effective, e.g. some types of Neuroendocrine Cancer (NETs). In general, well differentiated NETs do not normally show a high degree of sensitivity to chemotherapy, although some primary locations fare better than others. However, many of the treatments for NET Cancer are somewhat harsh, have long-term consequences, and have no visible effects. NET patients are often said to “look well” but that doesn’t mean they are not struggling behind the scenes or under the surface. Read more here. P.S. Afinitor (Everolimus), Sutent (Sunitinib) are not chemo – Read more here.
Myth 8: All diarrhea is caused by carcinoid syndrome
Not true. It could be one of the other syndromes or tumor types or a side effect of your treatment. Check out this post.
Myth 9: Neuroendocrine Tumours is a ‘good cancer’
Not true. Simply, no cancer is good. Some are statistically worse than others in prognostic terms, that’s true…… but living with NETs is very often not a walk in the park. However, no one cancer is better to get than any other – they’re all bad. Read more here.
Myth 10: Every NET Patient was misdiagnosed for years
Not true. Many NET Patients are correctly diagnosed early on in their investigation and in a reasonable time. This myth is perpetuated because of two things: firstly, on forums, the ratio of long-term misdiagnosis is high creating a false perception; and secondly, the method of capturing patient surveys is not extensive enough – again creating a false perception. In fact, the latest and largest database analysis from US indicates earlier diagnosis is improving, with more and more NETs being picked up at an early stage. Read more here.
Myth 11: Somatostatin Analogues are a type of Chemotherapy
Not true. Somatostatin Analogues (e.g. Octreotide and Lanreotide) are not chemotherapy, they are hormone inhibiting drugs. They are more biotherapy. As the drugs latch onto somatostatin receptors, they are more targeted than systemic. For the record, Everolimus (Afinitor) and Sunitinib (Sutent) are not chemotherapy either. Read more here.
Myth 12: Stuart Scott (ESPN) and Audrey Hepburn had Neuroendocrine Cancer.
Not true. This is a common misunderstanding within the community. They both had Pseudomyxoma Peritonei (PMP). Read more about PMP here.
Myth 13: I’ve been diagnosed with Neuroendocrine Tumours – my life is over
Not true. Many patients live a very long time and lead fairly normal lives with the right treatment and support. It’s difficult but I try not to use ‘I can’t’ too much. Read more here.
Myth 14: There are only a handful of Neuroendocrine specialists in the world
Not true. There are many specialists in many countries. Get links to specialists by clicking here.
Myth 15: The Ga68 PET scan is replacing the CT and MRI scan in routine surveillance for all NET Patients
Not true. It is actually replacing the Octreotide Scan for particular purposes, or will eventually. Read more by clicking here.
Myth 16: All NET Patients are Zebras
Not true. They are in fact human beings and we should treat them as such. Please don’t call me a zebra and please don’t use the term on my social media sites, I refuse to perpetuate this outdated dogma.
Myth 17: Multiple Endocrine Neoplasia (MEN) is a type of Neuroendocrine Tumour
Not true. Multiple Endocrine Neoplasia are syndromes and inherited disorders. You can have MEN and not have any tumours. However, these disorders can put people at more risk of developing Neuroendocrine or Endocrine Tumours. Read morehere
Myth 18: Palliative Care means end of life or hospice care
Not true. Palliative care is specialized medical care that focuses on providing patients relief from pain and other symptoms of a serious illness. A multidisciplinary care team aims to improve quality of life for people who have serious or life-threatening illnesses, no matter the diagnosis or stage of disease. Read more here
Myth 19: Serotonin is found in foods
Not true. Serotonin is manufactured in the body. Read more here
Myth 20: NETs cannot be cured
Not true. If caught early enough, some NETs can be treated with curative intent (totally resected) with little or no further follow up. It says this in ENETS and NANETS publications which are authored by our top specialists. If we can’t believe them, who can we believe? Read more here.
Myth 21: Pancreatic Enzyme Replacement Therapy (Creon etc) is only for pancreatic patients
Not true. It’s for any patient who is exhibiting exocrine pancreatic insufficiency. Read more here.
More to follow no doubt
For general cancer myths and the dangers of fake health news, please see my ARTICLE HERE
Thanks for reading
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OPINION. In the last 24 months, there seems to have been announcement after announcement of new and/or upgraded/enhanced diagnostics and treatment types for Neuroendocrine Cancer. Increased availability of radionuclide scans, increased availability of radionuclide therapies, combination therapies, increased availability of somatostatin analogues, biological therapies, enhanced surgical and minimally invasive techniques, new oral drugs for carcinoid syndrome, more trials including immunotherapy. Admittedly, some of the announcements are just expansions of existing therapies having been approved in new regions. Compared to some other cancers, even those which hit the headlines often, we appear to be doing not too badly. However, the pressure needs to stay on, all patients, regardless of where they live, need access to the best diagnostics and treatments for them; and at the requisite time. This alone is one very big unmet need in a whole range of countries still lacking.
The ‘War on Cancer’ forgot about Neuroendocrine
The ‘war on cancer’ has been around for the last 50 years, it’s still being waged. There are now more ‘fronts’ and it’s taking longer than thought to find the ‘cure’. Despite this 50 year war, it seems like there’s only been a war on Neuroendocrine Cancer for the last 10 of those years. I guess they were focused on the big cancers and/or the seemingly impossible ‘universal cure’. Prior to that, for NETs, there is only evidence of some skirmishes, more like guerrilla warfare. Now we have a developed nuclear capability! I believe the turning point was the SEER database work carried out by Dr James Yao in 2004 who confirmed the incidence had grown by 400% in 3 decades, i.e. confirming it was no longer rare. The rise of both incidence and prevalence was then amplified in the follow on ‘2012’ study (Desari et al) which confirmed a 640% increase in 40 years.
Let’s not forget about the consequences of cancer
It is true that half of people diagnosed with cancer now survive for at least ten years. Many live for years with cancer, on ‘watch and wait’ or going through various treatments and tests; their future remaining uncertain. For this group, and even for those whose treatment has successfully removed or shrunk their tumour, the struggle with the consequences and late effects of cancer and its treatment can last for years. Many Neuroendocrine Cancer patients fit into this category.
There’s a lot of work going on within all cancer communities to address the unmet needs of cancer patients who are now living with cancer rather than dying of it. Clearly we need this type of support in the NET world. The issue has been discussed at ENETS for the last two years and I was pleased to have asked the very first question about this particular unmet need, emphasising we need more support for those living with Neuroendocrine Cancer, including research into their common issues. I’ve yet to see any concrete output from the two year’s worth of campaigning.
Unmet Needs for NETs
So, there’s a lot of treatments for many types of Neuroendocrine Cancer out there, just not everyone has access to them – therefore an unmet need at the international level. Others are earlier diagnosis, access to multi-disciplinary teams (MDT), ability to access quality information at diagnosis and beyond including clinical trials, funding, accurate national registries to improve statistics and more treatments fot some of the less common types. One area where I feel there is a huge unmet need is in the area of patient support following diagnosis. Although some countries are more advanced than others in this area, even in the so-called advanced countries, there are huge gaps in provision of long-term support for those living with Neuroendocrine Cancer. For example, physicians need to focus more on:
Late diagnosis. People will be dealing from the effects of late diagnosis which has resulted in metastatic disease – and some people will have been fighting misdiagnosed illnesses for years. That takes its toll.
Consequences of Surgery. People will have had surgery which in many cases is life changing – various bits of the gut (gastrointestinal tract) are now missing, lungs are now missing – many other locationswill have been excised or partly excised. These bits of our anatomy were there for a purpose and QoL takes a hit when they are chopped out.
Inoperable Tumours and Syndromes. People will be dealing with remnant and/or inoperable tumours which may or may not be producing an associated NET syndrome (some of the symptoms can be rather debilitating in the worst cases)
Consequences of Non-surgical Treatment. Additionally, people will be dealing with the side effects of multi-modal non surgical treatments, such as somatostatin analogue hormone therapy (Octreotide/Lanreotide), chemotherapy, biological therapy (mTOR inhibitors) (i.e. Everolimus (Afinitor)), biological therapy (protein kinase inhibitors (i.e. Sunitinib (Sutent)), radionuclide therapy (i.e. PRRT). Whilst it’s great there are a wide range of therapies, they all come with side effects.
Secondary Illnesses and Comorbidities. Some people will have gained secondary illnesses in part due to the original cancer or treatment – e.g. somatostatin analogue hormone therapy can have a side effect of increasing blood sugar to diabetic levels. There are many other examples.
Finances. NET Cancer can be an expensive cancer to treat and this is exacerbated by the length of time the treatment lasts. A highly prevalent cancer, treatment is for life. It follows that NET Cancer is an ‘expensive’ cancer to have. Whilst most people have access to free public services or private insurance, many people will still end up out-of-pocket due to their cancer.
Emotional Aspects. Many NET patients are kept under surveillance for the remainder of their lives. With that comes the constant worry that the cancer progresses, tumours get bigger, new tumours show up, treatments are denied (i.e. PRRT in the UK). It’s no surprise that anxiety and depression can affect many patients in these situations. To some extent, there can be a knock-on effect to close family members and carers where applicable.
As I said in my question to the panel, even if you found a cure for NETs tomorrow, it will not replace the bits of my GI tract excised as part of my treatment. For many people, even ‘beating’ cancer might not feel much like a ‘win’. It’s a two-way street though – we need to work with our doctors, trying to change lifestyles to cope better with some of these issues. This is why it’s really important to complete patient surveys. However, my point is this: more research into some of these issues (e.g. nutrition, optimum drug dosage, secondary effects) and earlier patient support to help understand and act on these issues, would be good starters. I think some centres are doing elements of this type of support but we need a guideline generating in national and international groupings so that that others can be persuaded to formally introduce it.
“Adding life to years is as important as adding years to life”
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I recently wrote a blog called Neuroendocrine Cancer – Exciting Times Ahead! I wrote that on a day I was feeling particularly positive and at the time, I wanted to share that positivity with you. I genuinely believe there’s a lot of great things happening. Don’t get me wrong, there’s a lot still to be done, particularly in the area of diagnosis and quality of life after being diagnosed. However, this is a really great message from a well-known NET expert.
In an interview with OncLive, Jonathan R. Strosberg, MD, associate professor at the H. Lee Moffitt Cancer Center in Florida, discussed his presentation on NETs at a recent 2016 Symposium, and shed light on the progress that has been made in this treatment landscape.
OncLive: Please highlight some of the main points from your presentation.
Strosberg: The question I was asked to address is whether we’re making progress in the management of NETs, and I think the answer is unequivocally yes. Prior to 2009, there were no positive published phase III trials.
Since then, there have been 8 trials, 7 of which have reached their primary endpoints. So it’s been a decade of significant improvement. And even though none of these studies were powered to look at overall survival as an endpoint, we’re certainly seeing evidence of improvement in outcomes.
OncLive: What are some of the pivotal agents that you feel have impacted the paradigm in the past several years?
Strosberg: The first group is the somatostatin analogs. We use them to control hormonal symptoms like carcinoid syndrome, but with the CLARINET study, we now know that they substantially inhibit tumor growth.
The next significant drug we use in this disease is everolimus (Afinitor), an oral mTOR inhibitor, which is now approved in several indications based on positive phase III studies. The first was in pancreatic NETs and subsequently, based on the RADIANT-4 trial, it was also approved in lung and gastrointestinal NETs. So that was an important advance.
The next important category of treatment is radiolabeled somatostatin analogs, otherwise known as peptide receptor radiotherapy. The one that’s been tested in a phase III trial is lutetium dotatate, also known as Lutathera. It was tested in patients with progressive midgut NETs and showed a very substantial 79% improvement in progression-free survival, and a very strong trend toward improvement in overall survival, which we hope will be confirmed upon final analysis.
OncLive: Are we getting better at diagnosing and managing the treatment of NETs?
Strosberg: Certainly. I think pathologists are better at making the diagnosis of a NET, rather than just calling a cancer pancreatic cancer or colorectal cancer. They’re recognizing the neuroendocrine aspects of the disease, and doing the appropriate immunohistochemical staining.
We also have better diagnostic tools. We used to rely primarily on octreoscan, and in many cases we still do, but there is a new diagnostic scan called Gallium-68 dotatate scan, also known as Netspot, which has substantially improved sensitivity and specificity. It’s not yet widely available, but it is FDA approved and hopefully will enable better diagnosis as well as staging in the coming years.
And, with the increase in number of phase III studies, we’re developing evidence-based guidelines, which will hopefully lead to more standardization, although knowing how to sequence these new drugs is still quite challenging.
OncLive: With sequencing, what are the main questions that we’re still trying to answer?
Strosberg: If we take, for example, NETs of the midgut, beyond first-line somatostatin analogs, physicians and patients often face decisions regarding where to proceed next, and for some patients with liver-dominant disease, liver-directed therapies are still an option.
For others, everolimus is a systemic option, and then hopefully lutetium dotatate will be an option based on approval of the drug, which is currently pending. Knowing how to choose among those 3 options is going to be a challenge, and I think there will be debates. Hopefully, clinical trials that compare one agent to another can help doctors make that choice. It’s even more complicated for pancreatic NETs. Beyond somatostatin analogs, we have about 5 choices—we have everolimus, sunitinib (Sutent), cytotoxic chemotherapy, liver-directed therapy, and peptide receptor radiotherapy. It’s even more challenging in that area.
OncLive: Are there any other ongoing clinical trials with some of these agents that you’re particularly excited about?
Strosberg: There’s a trial that is slated to take place in Europe which will compare lutetium dotatate with everolimus in advanced pancreatic NETs, and I think that’s going to be a very important trial that will help us get some information on both sequencing of these drugs, as well as the efficacy of Lutathera in the pancreatic NET population, based on well-run prospective clinical trials. I’m particularly looking forward to that trial.
OncLive: Looking to the future, what are some of the immediate challenges you hope to tackle with NETs?
Strosberg: One area of particular need is poorly differentiated neuroendocrine carcinomas. That’s a field that’s traditionally been understudied. There have been very few prospective clinical trials looking at this particular population, and we’re hoping that will change in the near future. There are a number of trials taking place looking at immunotherapy drugs. If these agents work anywhere in the neuroendocrine sphere, they are more likely to work in poorly differentiated or high-grade tumors, in my opinion, given the mutational profile of these cancers. So that’s something I’m particularly looking forward to being able to offer these patients something other than the cisplatin/etoposide combination that goes back decades, and is of short-lasting duration.
See more at: http://www.onclive.com/publications/oncology-live/2016/vol-17-no-24/expert-discusses-recent-progress-in-net-management#sthash.ypkilX2A.dpuf
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OK – we’ve gone through diagnosis, we’ve gone through treatment and now we need to live with the consequences of cancer and it’s treatment. Not a day goes by when I don’t feel some twinge or some minor pain and I think ‘what was that?‘. Fortunately, many things can just be day-to-day niggles. It’s the cancer …. easy to say, sometimes not easy to prove.
However, for Neuroendocrine Tumour (NET) patients who have had surgery, anything that seems like a bowel obstruction is quite a scary thought (I suspect this is also an issue for other cancer types). In fact, even before diagnosis, a bowel obstruction rears its head as it can be how the condition is diagnosed in the first place, i.e. pain leads to more pain and that can sometimes result in a visit to the ER/A&E which can very often lead to a scan and an incidental diagnosis of NETs (and I suspect some other cancers).
I guess this isn’t just a threat for those who’ve had intestinal NETs but others in the vicinity of the intestines could also have this issue – the abdominal cavity is full of organs all very closely packed together! Both the small intestine and the large intestine can become blocked and if it can’t be unblocked by non-surgical means, it can become a bit of a drama for the patient. Blockages can be full or partial so it can often be a tough call for the medical team due to the effects of the patient’s existing surgery including but not limited to previous surgical scarring (adhesions), mesentery or retroperitoneal fibrosis complications (read about that by clicking here). Clearing the blockage by non-surgical means is the optimum solution. The presentational symptoms and scans can give immediate clues. Although there are slightly different symptoms for large and small intestine (bowel) obstructions, the key symptoms of a blockage would appear to be:
Feeling bloated and full
Severe abdominal pain
Vomiting large amounts
Looking at some authoritative sites, the logical (and fairly obvious) decision steps seem to be:
Is there an obstruction or is the problem something else?
If an obstruction, where exactly is it?
What is causing the obstruction?
Are there any complications such as adhesions, twisted loops or hernias
In 2016, I had 3 bouts of constipation and I confess that a potential blockage did cross my mind on all 3 occasions. However, I was comforted by the fact that I had no nausea and/or vomiting which I suspect is one of the key symptoms indicating a blockage rather than just a sluggish system. Fortunately, on all 3 occasions, the matter settled following a few days of right-sided pain (RLQ). One occasion required lactulose but all three required patience sprinkled with a pinch of endurance! I have to say the lactulose experience was not a good one – fatigue, brain fog and general malaise …..but much better than surgery. If you have issues with ‘fear’ living with cancer, check out my 7 tips article by clicking here.
I’m once again making some adjustments to try to find the magic spot between stool frequency and bulk….. it’s really difficult and not an exact science. I’m suspecting diverticular disease might be playing some part as I was diagnosed with a mild version in 2008 spotted during a colonoscopy(a common problem when you’re over 50). Although that tends to be a left-sided problem, I remain conscious that my ‘new plumbing’ may not be the best representation of a conventional layout!
NET Patient Foundation are really good at producing cards and there’s one for this too! Here’s the back of it here:
Look on any site about Neuroendocrine Tumours (NETs) and you’ll find the term IBS (Irritable Bowel Syndrome) frequently mentioned. That’s because it’s a common misdiagnosis for many before being formally diagnosed with NETs.
But what exactly is IBS, why is it such a common misdiagnosis for many NET patients and how can these misdiagnoses be prevented or reduced in future? I just spent a few hours doing an online training course on IBS and I want to pass on some stuff I found to be very useful. I have never been diagnosed with IBS but having researched the issue through some training, I can understand why it might be in the thoughts of a general practitioner for many scenarios. Much of my research was focussed on the British Society of Gastroenterology (BSG) who sponsored the online course I completed which also used material from their magazine Gut, a leading international journal in gastroenterology.
What is IBS?
Irritable bowel syndrome (IBS) is a common, long-term condition of the digestive system. It can cause bouts of stomach cramps, bloating and excessive wind, diarrhoea and/or constipation, feeling of incomplete emptying, mucus in stool; and many other symptoms (see NHS IBS site) The symptoms vary between individuals and affect some people more severely than others. They tend to come and go in periods lasting a few days to a few months at a time, often during times of stress or after eating certain foods. IBS is a heterogeneous condition with a range of treatments. There are in fact different classifications of IBS and the diagram below supports the list with some context:
IBS-D – diarrhea based
IBS-C – constipation based
IBS-M – mix of both diarrhea and constipation
You can see why someone presenting with diarrhea or IBS-D type symptoms might be automatically assumed to have IBS despite the fact that these symptoms could also apply to many other conditions including several cancers. However, what I also found is that in the UK, there is now updated guidance from NICE (National Institute for Health and Care Excellence) to aid GPs and other physicians on how to properly diagnose IBS. In fact, the online course I undertook is one of many now being offered to medical staff as part of the new guidance. That sounds like a good thing in practice (although I did notice some differences between the BSG recommendations and what is published by NICE…….. £ )
How is IBS diagnosed?
That is considerably complex as the symptoms are fairly general. However, I was encouraged to find that doctors should assess any ‘red flag’ indicators that would need referral to secondary care before any firm decision on IBS was made. These include (but not limited to), unintentional and unexplained weight loss, rectal bleeding, family history of bowel or ovarian cancer, a change in bowel habit to looser and/or more frequent stools persisting for more than 6 weeks in a person aged over 60 years, anaemia, abdominal masses, rectal masses, inflammatory markers for inflammatory bowel disease. That’s very interesting because in 2010, after mentioning some unintentional weight loss, my GP said ‘anaemia’ to me and referred me to secondary care. Perhaps I was lucky but perhaps, my GP’s team were just professional and thorough? That said, if you’re with me so far, you can see why IBS might be an easy diagnosis to make for someone presenting with either diarrhea/constipation issues with no other obvious symptoms or abnormal test results (particularly IBS-D).
Why might NETs be frequently misdiagnosed as IBS?
Using the NICE guidelines, I noted there are a range of tests to preclude other diagnoses including: full blood count (FBC), erythrocyte sedimentation rate (ESR) or plasma viscosity, c‑reactive protein (CRP), antibody testing for Coeliac disease. Whilst abnormal results of these tests might show up something to investigate further (i.e. FBC – haemoglobin worked for me), none of them include looking ‘inside’ the patient and I guess there is a resource/finance issue involved here.
In fact, the guidelines also list a number of tests that are NOT necessary to confirm a diagnosis of IBS. These include: ultrasound, rigid/flexible sigmoidoscopy, colonoscopy, barium enema, thyroid function test, faecal ova and parasite test, faecal occult blood, hydrogen breath test. You can see the issues ………..
The guidelines go on to say that a diagnosis of IBS should be considered only if the person has abdominal pain or discomfort that is either relieved by defecation or associated with altered bowel frequency or stool form. This should be accompanied by at least two of the following four symptoms:
abdominal bloating (more common in women than men), distension, tension or hardness
symptoms made worse by eating
passage of mucus.
Other features such as lethargy, nausea, backache and bladder symptoms are common in people with IBS, and may also be used to support the diagnosis
I also noted that the causes of IBS are inextricably linked with Psychological issues and the guidance also includes therapies including cognitive behavioural therapies (CBT) relaxation therapies, and hypnosis.
So if you’re one of the unlucky ones who has presented with “IBS like” symptoms and have normal test results as per above, you may not get the opportunity to get to further testing to find the true diagnosis. It’s possible that you saw a physician who has not followed guidelines for diagnosing IBS, if indeed such guidelines were available to him/her. The inclusion of psychological issues also connects with many anecdotal stories of NET patients being told they needed psychological help before eventually being diagnosed with NETs.
I can see many similarities in the descriptions of IBS symptoms and the sort of things you can read on NET forums – curiously including the effects of NET Cancer surgery and other treatment after diagnosis.
Slight digression but if this subject is of interest, you may like to comment. I once said to my Oncologist that I felt as if I had IBS since my surgery and somatostatin analogue treatment. In fact, I told him that I thought my bowel was more than irritated, it was bloody angry 🙂 During my research, I couldn’t help noticing that some of the suggestions and recommendations for IBS are similar to that offered to a post surgical NET patient. You may therefore like my blog series on Nutrition which was co-authored by a NET specialist dietician who is also IBS aware.
Preventing or Reducing a Misdiagnosis of IBS (all illnesses)
The course looked at this angle as it was clearly keen to emphasise this to medical people going through the module. The NICE guidelines read like a process which must be strictly followed but at the end of the day, they are just ‘guidance’ and should not stop doctors thinking outside the box.
A recent study suggested that as many as 1 in 6 patients (~16%) with symptoms of IBS had another disease. Approximately 7% had Crohn’s disease, 3% coeliac disease, and 2% microscopic colitis when they were formally tested. Patients with IBS-diarrhoea predominant more often had abnormalities than those with IBS-constipation predominant (interesting for NETs). The paper stresses the importance of tailored investigation of patients presenting for the first time.
One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS. You can, if you wish, read the abstract of the paper on the link below.
The issue here is that people not meeting the criteria for further checks may be precluded for scans and other tests due to lack of clinical evidence and their diagnosis of IBS will stand. As this was a study, clearly some of them might have gone on to present with sufficient clinical evidence to warrant more checks and subsequent diagnosis of something else at a more advanced stage. Clearly this sounds familiar with NETs. However, looking at the figures above, I suspect the figures for NETs IBS misdiagnoses are pretty small in comparison to those who are correctly diagnosed with IBS. To put that into context (in the UK), according to the NHS, IBS is thought to affect up to one in five people (10,000,000 in UK alone) at some point in their life, and it usually first develops when a person is between 20 and 30 years of age and around twice as many women are affected as men. Compare that with a UK NETs prevalence of around 40,000 (guesstimate), you can see that a misdiagnosis of IBS for NETs, is not that common. However, one misdiagnosis is one too many.
Having done this course and read the accompanying references (some only abstracts), I can see the scope for people with many different illnesses being misdiagnosed with IBS. However, the use of alarm symptoms and ref flag indicators should be helping to reduce this. I’m guessing that many people in first line care may not be fully aware of the IBS guidelines to be able to take heed. I’m also guessing that in the UK (at least), a 10 minute appointment with a busy GP is just not going to solve some of these symptom clashes and many visits might be required to move forward.
It’s really difficult to advise anyone going through a diagnosis of IBS as to how to approach a physician who says they have IBS and they think this is wrong. In the case of NETs, other cardinal symptoms may be of use in convincing physicians (e.g. flushing). Armed with this knowledge, I would say to anyone who suspects NETs but are faced with an IBS diagnosis, take a copy of the BSG and NICE guidelines to your doctor and tick off all the differential ‘ref flag’ and ‘alarms’ issues ensuring that each has been tested before accepting the IBS diagnosis.
References used to support compilation of this blog:
It’s amazing to think that one minute I’m back from a holiday in the Caribbean and the next minute I’m being told the inside of my body is a ‘train crash’. Just how does that work? In July 2010, I said to the Gastroenterologist investigating my low hemoglobin “I’m not even feeling ill”. He sent me to an Oncologist who then told me that without treatment, the prognosis wasn’t good (i.e. I would eventually die). I also told him I wasn’t feeling ill ….as if my protest was somehow going to reverse the situation!
20 months prior I had a colonoscopy after a short-term change of stool colour. Nothing found.
I also had some very infrequent bouts of diarrhea – I don’t normally get diarrhea so it must be something I’d eaten……… I carried on.
I started experiencing ‘flushing’ sensations (hot but dry) some 6-9 months prior to diagnosis – Despite this being very strange, I kept this to myself and ……..I carried on.
I was exhausted – I blamed it on my appetite for work……..I carried on.
Boy, am I now in tune with my body! If you think something is wrong and it just isn’t normal, follow your gut instinct, see someone, see that someone again and then see someone else if necessary. Keep a detailed diary of your symptoms, do your homework and let the medical practitioner know everything. This is the least you can do. This is also extremely relevant after diagnosis.
Doctors don’t have a cure for your “stiff upper lip”, there is no prescription. Only YOU can take action. Now go see that doctor or at least talk to someone.
Procrastination, aided and abetted by your ‘stiff upper lip’ – it’s a killer.
Diarrhea can be a symptom of many conditions but it is particularly key in Neuroendocrine Tumour (NET) Syndromesand types, in particular, Carcinoid Syndrome but also in those associated with various other NET types such as VIPoma, PPoma, Gastrinoma, Somatostatinoma, Medullary Thyroid Carcinoma.
Secondly, it can be a key consequence (side effect) of the treatment for Neuroendocrine Tumours and Carcinomas, in particular following surgery where various bits of the gastrointestinal tract are excised to remove and/or debulk tumour load.
There are other reasons that might be causing or contributing, including (but not limited to) endocrine problems such as hyperthryoidism, mastocytosis or Addison’s disease (which may be secondary illnesses in those with NETs). It’s also possible that ‘non-sydromic’ issues such as stress and diet are contributing. It could be caused by other things such as Irritable Bowel Syndrome (IBS). Yes, believe it or not, NET Patients can get normal diarrhea causing diseases too!
I want to give a general definition of diarrhea as there are many variants out there. In general, they all tend to agree that diarrhea is having more frequent, loose and watery stools. Three or more stools per day seems to be the generally accepted threshold, although some sites don’t put a figure on it. It’s not pleasant and just about everyone on the planet will suffer it at some point in their life, perhaps with repeated episodes. Normally it’s related to some kind of bug, or something you’ve eaten and will only last a few days before it settles (acute diarrhea). Diarrhea lasting more than a couple of weeks is considered chronic and some people will require medical care to treat it. It can also be caused by anxiety, a food allergy/intolerance or as a side effect of medicine. Pharmacists and GPs will be seeing many patients with this common ailment every single day of business.
Diarrhea induced by a Syndrome
When you consider the explanation above, it’s not really surprising that diarrhea related symptoms can delay a diagnosis of Neuroendocrine Cancer (and most likely other cancers too, e.g. pancreatic cancer, bowel cancer). For example, diarrhea is the second most common symptom of Carcinoid Syndrome (Flushing is actually the most common) and is caused mainly by the oversecretion of the hormone Serotonin from the tumours. Please note diarrhea in other types of syndromes or NETs may be caused by other hormones, for example it may also be caused by excess calcitonin in the case of Medullary Thyroid Carcinoma or VIP in the case of a functional pNET known as VIPoma. I’ve heard stories of people being told they have IBS or something similar for years before they received what is now a late diagnosis and at an advanced cancer stage. This is only one of the reasons why NETs is not an easy condition to diagnose, although it is possible that some people actually had IBS and it was masking the NET. Even after treatment to remove or reduce tumours, many people will remain syndromic and need assistance and treatment to combat diarrhea induced by a NET syndrome (see below).
Diarrhea as a Consequence (Side effect) of Treatment for Neuroendocrine Cancer and Other Conditions
All cancer treatments can have consequences and Neuroendocrine Cancer is definitely no exception here. For example, if they chop out several feet of small intestine, a chunk of your large intestine, chunks (or all) of your stomach or your pancreas, your gallbladder and bits of your liver, this is going to have an effect on the efficiency of your ‘waste disposal system’. One effect is that it will now work faster! Another is that the less effective ‘plumbing’ may not be as efficient as it was before. There are also knock-on effects which may create additional issues with the digestive system including but not limited to; Malabsorption and SIBO. I recommend you read my posts on Malabsorption and SIBO.
Surgery can often be the root cause of diarrhea. A shorter gut for example, means shorter transit times presenting as increased frequency of bowel movements. Another example is the lack of terminal ileum can induce Bile Acids Malabsorption (BAM) (sometimes known as Bile Salts Malabsorption) in degrees of severity based on size of resection. Lack of a gallbladder (common with NETs) can also complicate. Bile Acids are produced in the liver and have major roles in the absorption of lipids in the small intestine. Following a terminal ileum resection which includes a right hemicolectomy, there is a risk that excess Bile Acids will leak into the large intestine (colon) via the anastomosis (the new joint between small and large intestines). This leakage can lead to increased motility, shortening the colonic transit time, and so producing watery diarrhea (or exacerbating an existing condition). Although this condition can be treated using bile acid sequestrants (i.e. Questran), it can be difficult to pinpoint it as the cause.
Surgery of the pancreas can also produce effects such as exocrine pancreatic insufficiency which can lead to a malabsorption condition known as steatorrhea which may be confused with diarrhea (although some texts call it a type of diarrhea). It isn’t really diarrhea but it may look like it given the presentation of the faeces and patients may suffer both diarrhea and steatorrhea concurrently. Patients will recognise it in their stools which may be floating, foul-smelling, greasy (oily) and frothy looking. Treatment options will mainly include the use of Pancreatic Enzyme Replacement Therapy or PERT for short (Creon etc).
Many non-surgical treatments can also cause diarrhea, including but not limited to; somatostatin analogues (see below), chemotherapy, biological targeted therapy (e.g. Everolimus, Sunitinib), radiotherapy.
Somatostatin analogues are an interesting one as they are designed to inhibit secretion of particular hormones and peptides by binding to the receptors found on Neuroendocrine tumour cells. This has the knock-on effect of inhibiting digestive/pancreatic enzymes which are necessary to break down the fat in our foods leading to Malabsorption of important nutrients. This may worsen the steatorrhea in pancreatic NET patients but also lead to steatorrhea in others with non-pancreatic locations who have been prescribed these drugs.
Other conditions may actually be the cause of the diarrhea or the treatment for those conditions. For example, it is possible that people actually do have Irritable Bowel Syndrome (IBS). Treatment therapy for common conditions may also be contributing, for example the use of Proton Pump Inhibitors for acid reflux.
Treatment for Syndrome Induced Diarrhea
Like many other NET patients, I’m on a 28 day injection of somatostatin analogues (in my case Lanreotide). Both Octreotide and Lanreotide are designed to reduce the effects of NET syndromes and therefore can often make a difference to syndrome induced diarrhea. These drugs also have anti-tumour effect and so even if you are not syndromic or they do not halt or adequately control syndrome induced diarrhea, they are still a valuable contribution to NET treatment.
Some syndromic patients find they still have diarrhea despite somatostatin analogues and they end up having ‘rescue shots’ or pumps for relief (both of these methods tend to be Octreotide based). (Hopefully they are not getting confused between diarrhea caused by the non-syndrome effects – see above). Some have more frequent injections of the long acting versions of somatostatin analogues which has the effect of increasing the dosage. There’s a new drug available for those whose carcinoid syndrome induced diarrhea is not adequately controlled or perhaps they are unable to have somatostatin analogues as a treatment. Telotristat Ethylworks by inhibiting tryptophan hydroxylase (TPH), a chemical reactor involved in the manufacture of serotonin, which is the main cause of syndrome induced diarrhea. It was approved by the US FDA in February 2017, EU areas in September 2017, and is on the way to being approved elsewhere. Read about this drug here.
Sorting out the symptoms – post diagnosis
I like to describe this as the Neuroendocrine Cancer jigsaw. It’s a really difficult one and sometimes you cannot find a piece, or the pieces won’t fit. However, metaphorically speaking, the missing piece might be a NET specialist presentation, a comment, statement or view from another patient, a link to an article from a reputable source, or even something you do to improve your lot – there might even be trial and error involved. It might even be this blog post!
How do you work out whether diarrhea is caused by a hormone producing tumour or by the side effects of treatments? There’s no easy answer to this as both might be contributing. One crude but logical way is to just accept that if you have normal hormonemarkers, for example 5HIAA (there could be more for other tumour/syndrome types), and you’re not really experiencing any of the other classic symptoms, then your syndrome might be under control due to your treatment (e.g. debulking surgery and/or somatostatin analogues, or another drug). My Oncologist labels me as ‘non-syndromic’ – something which I agree with. I’m 99.999999% sure my issues are as a result of the treatment I’ve had and am receiving.
This disease is so individual and there are many factors involved including the type of syndrome/NET, patient comorbidities and secondary illnesses, consequences of the surgery or treatments performed, side effects of drugs – all of which is intermingled with suspicion and coincidence – it’s that jigsaw again! I always like to look in more detail to understand why certain things might be better than others, I always challenge the ‘status quo’ looking to find a better ‘normal’. I really do think there are different strategies for syndrome induced diarrhea and that which is a result of treatment or a side effect of treatment. There’s also different prices, with inhibitors costing thousands, whilst classic anti-diarrhea treatments are just a few pennies. Adjustments to diets are free!
When I was discharged from hospital after the removal of my small intestinal primary, I was in the toilet A LOT (I was actually in the toilet a lot before I was discharged – check out my primary surgery blogs here) . My surgeon did say it would take months to get back to ‘normal’ – he was right and it did eventually settle – although my new ‘toilet normal’ was soft and loose and several times daily. My previously elevated CgA and 5HIAA were eventually back to normal and my flushing had disappeared. I didn’t have too many issues with diarrhea before diagnosis. Deduction: my issues are most likely not syndrome induced.
I read that many people find basic ‘Loperamide’ (Imodium) helps and I tend to agree with that if you are non syndromic and just need that little bit of help. I decided long time ago I would not become ‘hooked’ and only really take it for two purposes: 1) if I have a bad patch and 2) if I’m going on a long journey (i.e. on a plane perhaps). I estimate I’ve used 4 packets in as many years. Loperamide decreases the activity which causes intestinal motility (peristalsis). This has the effect of increasing the time material stays in the intestine therefore allowing more water to be absorbed from the fecal matter. Ideal for those with a shorter bowel due to surgery and advice from a medical professional is always advisable. To reduce the risk of malabsorption induced diarrhea and steatorrhoea, both of which can lead to loss of valuable nutrients, the use of Pancreatic Enzyme Replacement Therapy (PERT) might need to be introduced as required by your NET specialist.
Have a look at Enterade – the results from trials look good.
Clearly, I cannot offer any professional medical advice on coping with diarrhea, I can only discuss my own situation and what I found worked for me. Don’t forget, like many diseases, what works for one, might not work for another. However, I did tackle my problems following the advice of an experienced dietitian who specialises in NET Cancer. That said, I was ‘sleep walking’ for over 2 years thinking my issues were just part of the way things were after my treatment. I was wrong about that!
As for my own strategy, here’s things that helped me:
made some changes to diet(they were not huge changes),
maintained a diary to help with monitoring progress or setbacks,
hydration is also important (….still working on that one).
started taking PERT (Creon) on 23 Dec 2017 (changed to Nutrizym Feb 2019) but looks reasonably positive so far.
With no fancy and expensive drugs, I’ve gone from 6-8 visits to 1-2 visits (as a daily average, it’s actually 1.5). This didn’t happen overnight though, it took a lot of time and patience. All of this doesn’t mean to say I don’t have issues from time to time …… because I do!
In summary, I think it’s important that people be sure what is actually causing their diarrhea after diagnosis so that the right advice and the optimum treatment can be given.
Listen to Dr Wolin talking about this particular jigsaw puzzle – click here
Also see a nice article that come out of NANETS 2017 – click here
Of course, some people sometimes have the opposite effect but that’s in another blog here – Constipation
6 years ago today Chris and I flew off to Barbados on holiday. Both of us were looking forward to a nice break after a hectic start to 2010. When we got back, we both agreed it was the most relaxing holiday we had ever been on. It was heaven.
However, whilst I was lying on a sunbed soaking up the Caribbean sun drinking ‘pina coladas’, Neuroendocrine Tumours were growing in my small intestine, spreading into my mesenteric lymph nodes, into my liver, into my left armpit and into my left clavicle area. The excess serotonin being released was causing a dense fibrotic retro-peritoneal reaction (desmoplasia) encircling my aorta and cava almost blocking the latter. That problem alone might have been the end of me.
Just prior to going on holiday, I knew I had an issue with a low haemoglobin blood test and was waiting to be told what would happen next. However, I wasn’t even the slightest bit worried, this was ‘something and nothing’ despite the fact that I’d been ignoring a minor flushingsensation for 6 months. When we returned from holiday, there was a letter of referral to a local anaemia clinic in 5 weeks time. To cut a long story short, I bypassed that and went straight to a Gastroenterologist and was diagnosed very shortly after with metastatic Neuroendocrine Cancer.
One of the key aims of my blog is to create more awareness of Neuroendocrine Cancer (or NETs), its peculiarities, its effects, its ability to deceive, its ability to kill if left undetected and/or untreated; and its impact on Quality of Life (QoL). There are millions of people out there doing similar with thousands of other conditions. That means even to stand out a little, messages must be compelling, must attract attention; and must catch people’s interest.
In the last 36 months, I’ve generated a few ‘different’ awareness campaigns, some of which have been more successful than others and I learn from this. One of them is actually now the most tweeted post about NETs on twitter. Fortunately, I have had significant help from YOU because if you did not share my posts and blogs, they would not have the potential reach they currently do and would not, therefore, attract the new audiences I’m looking for (….and finding!). The same applies to Facebook, twitter and other parts of the social media universe. I thank you all for the help to date. However, the job is far from finished!
My main campaigns are listed here so please help yourself to the ones you like and feel free to support or sponsor. Please note there are social media sharing buttons at the bottom of each post – or just simple cut and paste as required.
Neuroendocrine Cancer would love you to ignore this post. This is a reverse psychology message which is designed to attract attention – and it does!. It is currently the most tweeted post in the history of NET Cancer awareness. If you are on twitter, please retweet the original post (quoting it in a new post is also great but please also retweet the original). The tweet can be found by clicking here. It’s also a great awareness post for any type of social media so please share as it gives a really simple and yet compelling awareness message about the danger of NET Cancer and ignoring symptoms, including after diagnosis. Click here then share.
Living with Neuroendocrine Cancer – it takes guts! This is a powerful message which lets people know what effects the consequences of Neuroendocrine Cancer and its treatment have on people’s lives. It’s not a pity party – I don’t do those (as you well know).
I also emphasise that it’s not all about diagnostic difficulties (as important as that might be), more focus needs to be placed on LIVING with NETs given that it is a highly prevalent cancer, and no longer rare.
The diagnostic angle was relevant 10 years ago but the focus needs to become much wider thus why the community needs to shift from the ‘same old same old’ to a ‘different new’. This post has attracted much interest from new audiences in the wider healthcare world. Read and share it by clicking here
Neuroendocrine Cancer – ssh! Can you hear it? This is the NETs is ‘silent’ theme and attracts a lot of support. This really drives home the devious nature of NETs, the fact that it can be a very silent cancer until it’s too late and the difficulties that it presents with accurate diagnoses and subsequent ongoing monitoring. The post can be found by clicking here
The Human Anatomy of Neuroendocrine Cancer. This is a campaign to point out that NET Cancer is not confined to a particular part of the body and raises the issue of misdiagnosis, incorrect naming and recording of cancer types; and the loss of awareness opportunities, particularly when famous people are involved. I never get fed up of sharing this one and it cannot be shared too many times! Please feel free to share the hell out of this one. The post can be found by clicking here
This is an awareness message to emphasize that there are a number of different syndromes involved in NETs in different parts of the body and that terminology and understanding is important to get the awareness messages right. Click here.
Every day is NET Cancer Day. This post has had the largest number of 5 star ratings input by readers indicating support for my awareness strategy. Don’t get me wrong, 10 Nov is special but the other 364 days also present awareness opportunities. You can read this blog by clicking here. You can also register for my NET Cancer Day Social Media Event leading up to 10 Nov by clicking here and select ‘Going’ (then invite others please). On this event, Every Day is NET Cancer Day!
Let’s raise our ‘sites’. This awareness message also emphasizes the anatomy of NETs and the importance of the correct terminology in order to get the optimum and accurate awareness messages over. I’m using the word ‘sites’ as a take on ‘sights’ – someone picked me up for spelling last time I posted! Click here to read.
The 9 posts above comprise around 20% of my total blog hits and these are the ones which are attracting new audiences who now know about Neuroendocrine Cancer and are telling others. Please help me build on this.
Neuroendocrine Cancer can be silent but we shouldn’t be!
OPINION. When I was being officially told I had an advanced and incurable cancer, I did what most people seem to do on films/TV ….. I asked “how long do I have“. The Oncologist said ” … perhaps just months“. That must have been quite a shock because for a few moments after that, I heard nothing – my brain was clearly still trying to process those words – I wasn’t even feeling unwell! The really important bit I missed was him go on to say “…but with the right treatment, you should be able to live for a lot longer”. Fortunately, my wife Chris heard it all and I was refocused. “OK Doc – let’s go” I said. Always take someone with you to take notes at important meetings with Oncologists!
I continue to see quite a few posts and articles about death and dying and I noticed some patients were using the word ‘terminal‘ to describe Neuroendocrine Cancer, despite in some cases, having been diagnosed some years ago. This label is not just confined to use within Facebook forums, I’ve also seen this on wider social media including twitter, blogs and newspaper items. For some, this appears to be the prognosis given to them by their doctors. I find this surprising. However, I’m much less surprised to see many comments on forums from people who had been told the worst by their doctors but were still alive and kicking WAY beyond those worst case prognostic statements.
Definitions are important so what does ‘terminal cancer’ actually mean?
I’m conscious there are legal ramifications with the definitions (wills, life insurance, disability etc) and that these may differ on an international/federal basis. I therefore intentionally confined my searching to a couple of ‘big hitter’ and ‘authoritative’ sites:
Cancer Research UK defines terminal as “When cancer is described as terminal it means that it cannot be cured and is likely to cause death within a limited period of time. The amount of time is difficult to predict but it could be weeks to several months”.
The American Cancer Society defines terminal as “an irreversible condition (it cannot be cured) that in the near future will result in death or a state of permanent unconsciousness from which you are unlikely to recover. In most states, a terminal illness is legally defined as one in which the patient will die shortly whether or not medical treatment is given.”
Can terminal as defined above be applied to Neuroendocrine Cancer?
I’m sure it can, e.g. with very advanced and very aggressive disease and for any grade when taking into account the condition of the patient and other factors (secondary illnesses/comorbidities, refusal of treatment etc). Clearly, that is a terrible situation. I’m also conscious that some people do eventually die because of this disease or its consequences and that is also terrible.
How long is a piece of string?
I think with most Neuroendocrine Cancer patients, “how long do I have” can be a tough question to answer. Thinking back to my own situation, although it was an obvious question to ask my Oncologist, I can see it might have caught him unawares. I suspect he was erring on the side of caution as I don’t believe he had formulated my treatment plan ….. i.e. my case had not yet been looked at by a Multi-Disciplinary Team (MDT), a bit like a ‘Tumor Board’. I had already been confirmed Grade 2 (via liver biopsy) and my CT scans were indicating widespread disease. I was yet to have an Octreotide scan and the conventional biochemical markers (CgA and 5HIAA). I suspect, faced with my question, he went for the worst case, based on the statistics he had access to at the time. What I now know is that, in the year of my diagnosis, the median survival was 33 months in patients with advanced Grade 1/Grade 2 NETs with distant metastasis. These statistics are certainly better today but my Oncologist was probably on the right track. However, at no time did he use the word ‘terminal’.
The Cancer story is changing
What I also found during my research is that as more and more people in the UK are now living with cancer (all cancer) rather than dying from it, there is a new class of patients emerging – Macmillan UK call this “treatable but not curable” and I believe this is very relevant to Neuroendocrine Cancer. I touched on this in an awareness blog entitled “Living with Neuroendocrine Cancer – it takes guts“. You will find some data in this blog about a major increase in the amount of people with cancer who eventually die of something else (…… basically it has doubled). For many, Cancer is no longer a death sentence. I do accept that it can be difficult to live with certain cancers and this is also covered in my “it takes guts” blog linked above.
Survivorship and Hope
You can find numerous examples of long-term survivors of advanced Neuroendocrine Tumours on the ‘airwaves’, many with a relatively good quality of life (QoL). I don’t normally pay much attention to prognostic data, I take my lead from the huge number of patients living a long time with Neuroendocrine Cancer. However, I was particularly interested to read a set of USA statistics from NOLA (Boudreaux, Woltering et al) which said “Our survival of stage IV midgut NET patients that we performed surgical debulking on was published in the Journal of the American College of Surgeons in 2014. It showed our 5, 10 and 20-year survival rates were 87%, 77% & 41% respectively. It’s also worth noting the comparison with the 2004 SEER database analysis which listed the 5 & 10 year SEER survival at 54% and 30% respectively”. Clearly, the NOLA figures are guidelines (and only for midgut) but they do seem to reflect my previous statement about seeking out positives rather than dwelling on the negatives. The SEER 2012 figures are much better than the 2004 versions stating “Survival for all NETs has improved over time, especially for distant-stage gastrointestinal NETs and pancreatic NETs in particular, reflecting improvement in therapies.
Exciting times ahead
On the subject of therapy improvement, there has been a plethora of new treatments coming online and more entering and progressing through the approvals pipeline. Check out my article entitled Exciting Times Ahead. Also listen to a NET Expert along the same lines. PRRT is making a real difference.
Following my diagnosis in 2010, I went on to receive really good treatment and it continues to this day with Lanreotide backed up by a rigorous surveillance regime (and this is backed up by my own advocacy!). However, I have totally accepted the fact that I have metastatic Neuroendocrine Cancer and that it cannot be cured. By the way, I intentionally used ‘metastatic‘ rather than Stage IV. Mention of Stage IV can set off alarm bells and send the wrong message to the recipient. I don’t believe Stage IV has the same ‘red flag’ meaning for well-differentiated NETs as it does with more aggressive cancers of the same stage. Given what I know now, I would certainly challenge any doctor who told me I had a ‘terminal disease’ and at the same time told me I had a slow-growing well differentiated Neuroendocrine Cancer.
I now live with this disease (….and it’sconsequences) and do not feel like I’m dying of it. Moreover, I most certainly do not see myself as a ‘terminal’ cancer patient, particularly as I’ve now been living with it since 2010.
Over the last few months, I’ve seen quite a few posts entitled “Not all Cancer is pink”. I suspect it’s a reference to the ubiquitous publicity that many women’s cancer related advocates, bloggers and organisations attract.
Those who use this phrase are perhaps concerned there is an imbalance and inherent unfairness in the distribution of support and are frustrated that their own cancer does not fare as well publicly? I share that frustration, however, I take my hat off to the battalions of advocates, bloggers and organisations who work very hard for breast and the various gyneacological cancers whether they push pink or not (and for the record, they don’t all push or even agree with the ‘pink’ thing).
I’ve even seen this term used within my own community – ‘Not all cancer is pink, some are black and white’. This is clearly an attempt to tie in the well-known ‘pink’ to the not so well-known ‘black and white’. Notwithstanding the potential for upsetting hard-working women’s cancer organisations and the fact that those in the NET community who push the pink ‘insult’, do not have a corresponding ‘Not all cancer is blue’ article, I also think we might be missing a trick.
And here’s the trick which is my alternative view on where we should be focused – Not all Cancer is black and white and nothing in cancer is ever black and white. As I don’t want to indulge in‘Cancer Olympics’ (it can backfire), I’m clearly talking about the context of the phrase ‘black and white’ rather than the ribbon colours.
Let me explain my logic. There are two sides to most people’s experience or perception of cancer. Firstly, symptoms appear, a diagnosis is made, treatment is applied and if it works, the patient will hopefully go into remission after a period of time, normally 5 years. The other side is that sadly, some people may not survive the ordeal and that even applies to certain so-called ‘pink’ cancers (metastatic breast cancer for example). Clearly there are variations of my very simple binary explanation but these two outcomes are very common scenarios.
However, many cancers (including my own Neuroendocrine Cancer) are often silent, produce vague symptoms, are difficult to diagnose, treatment plans can be a challenge, most metastatic patients and many with other stages will never really be cured, and will need lifelong support (another challenge we need to focus on). They are extremely cunning and sneaky. Neuroendocrine Cancer has many ‘grey’ areas. Clearly there are also variations on this theme but with many scenarios and different outcomes.
Not all cancer is pink, that’s true. However, not all cancer is ‘black and white’ – some can be extremely ‘grey’. This is one of the reasons why I say “Every single day is NET Cancer Day“.
If we want more attention, let’s learn from other cancer awareness activities instead of attacking their colours. Lesson No 1 – they don’t use animals as icons because people won’t take them seriously.
I recently blogged about a well-known BBC political reporter who has a Neuroendocrine Cancer with a Lung Primary. However, in the usual media ‘double speak’ which can sometimes pervade the coverage of such events, he is said to have Lung Cancer. As I said in that article, sometimes with Neuroendocrine Cancer – the devil is in the detail and you just need to dig to find it. Annoying, we shouldn’t need to dig as he doesn’t have Lung Cancer. I wrote about this anatomical issue here. This is exactly what happened to Steve Jobs and Aretha Franklin.
No sooner had I published the Nick Robinson article, I was alerted to the broadcasting of a film about rock star Wilko Johnson who has the most amazing story to tell. Wilko is a former member of Dr Feelgood, a famous British R&B band who were pretty popular in the 60s/70s/80s and remain so today.
In 2014, Wilko was diagnosed with Pancreatic Cancer and was told he had a year to live. One year later, a photographer friend Charlie Chan (who just happened to be a doctor) commented that he looked too well and was still doing his routine and fast-paced musical performance, that something was perhaps not right about this diagnosis. To cut a long story short, he was retested and re-diagnosed with a Neuroendocrine Cancer with a primary in the pancreas. However, it was a large tumour (7 lbs in weight and the size of a melon) and the surgery was ‘extreme’ taking 11 hours and with a lower than normal chance of survival. He seems to be doing OK so far. However, the ‘double speak’ is also being used in his case as nearly all reports and news articles state he has Pancreatic Cancer.
Until I saw the film on BBC1 a few days ago, I hadn’t realised the film was even being made. The first half of the film is really about a man who thinks he is going to die and he doesn’t really have an issue with this – he misses out all the usual emotions moving straight to acceptance. He also decided to do a ‘final’ gig teaming up with Roger Daltrey (The Who) – you can watch this from a link below.
I suspect the film sponsors were totally surprised to be continuing the film to include his re-diagnosis, his surgery and the beginning of his recuperation (I suspect Wilko was more surprised though). Having now watched the full 90 minutes, I can say I enjoyed it (particularly the second half) but I suspect it won’t be everyone’s ‘cup of tea’. However, it gives an insight into the man himself along with his journey. Some of the music clips will get your feet tapping. A little bit of me wants to get to know him more as I hadn’t realised he is a bit of a philosopher (ex-English teacher) and an astronomer in addition to being a rock star and generally down to earth ‘geezer’. There are some good quotes in the film including “if the cancer is going to kill me, I don’t want it to bore me”. This probably explains his very positive attitude when told he would die and decided his ‘new normal’ would be his usual normal!
There is not a single mention of Neuroendocrine Cancer (unfortunately). However, the film came out on DVD 11 Dec 2015. There might be limitations on playback in non-UK countries but WATCH THE TRAILER click here
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:
There’s also an interesting interview with Roger Daltrey (member of The Who and friend of Wilko). There is more detail of this “other” cancer and his recuperation but again the word Neuroendocrine is not mentioned. Watch Here
Here is the gig with Roger Daltrey, which Wilko thought this would be his last. Watch Here
Having watched the film, I now have more sympathy with Wilko’s position and there’s a bit of me thinking we might hear some more about his condition downstream ………..
23 May 2016 – two new clips to add to the story:
1. Newspaper interview 21 May 2016. Click Here.
2. Interview with Victoria Derbyshire on 23 May 2016. Click Here.
A couple of years ago, I received a request from a reader asking if I would write an article about all the symptoms experienced by a Neuroendocrine Cancer patient and how to sort out what is and what isn’t associated with NETs.
Although I chuckled and raised eyebrows at the request, inside I was genuinely humbled that someone thought I was capable of achieving this herculean task. I actually gave it quite a bit of thought to the point of compiling a matrix of types of NET, main symptoms, cross-referenced with the symptoms of the most common reported comorbidities. After it started to look like it might be bigger than the Empire State Building, I came to the conclusion that it’s an almost impossible task for a wee Scottish guy with less common disease 🙂 I also started to suspect that even the world’s top NET experts had not accomplished it either.
Here’s a picture of my work to date:
I have, however, dabbled in attempts to work out my own problems over the past few years. NETs can present with a ‘syndrome’ – a bunch of symptoms normally caused by excessivehormone secretion, some of which are particularly vague and can sometimes continue to cause issues after treatment and beyond – it’s a real witch’s brew of symptoms. They can also cause non-syndromic issues pertaining to treatment side effects and it must also be noted that even NET patients get regular illnesses which adds to the issues healthcare professionals and patients face in monitoring NETs.
In my article “Neuroendocrine Cancer Syndromes – early signs of a late diagnosis”, I focused on the key symptoms experienced pre-diagnosis and then discussed how you might go about sorting out the symptoms from main side effects post treatment (another regular conundrum for most). On a similar subject, you might want to check out my 5 E’s blog for carcinoid syndrome. I also compiled an article about the source of flushing and diarrhea given there were many differential diagnoses and not just syndromes.
NETs vs Other Illnesses
Adding another jigsaw piece to the issues with cancer and side effects – common comorbidities (many of an endocrine nature) can arise simultaneously. Is it connected with NETs are just another illness to manage alongside? All of these factors can make it really difficult to determine the source of the symptoms. I’m always conscious that the majority of NET patients are in their 5th decade onward and at an age where things start to go wrong quite naturally due to ‘time’ and ‘wear and tear’.
Here’s one classic example of this problem, I can see many people on forums also have diabetes (an endocrine disease). In the United States alone, nearly 7 million people have undiagnosed diabetes, according to the American Diabetes Association. I can also see from the news in UK, that this is becoming a much bigger deal too – a report published in Feb 2018 claims that diagnoses have doubled in 20 years. I’ve used the diabetes link as an example, there will be many other very common factors at play, e.g. hypothyroidism an age and gender relation issue. It is certainly possible that many of the problems people face might just be an as yet undiagnosed/underlying condition, unconnected with NETs. To quote the great Dr Eric Liu, “even NET Patients get regular illnesses”. Working it out is rather difficult though. Sometimes pragmatism is required.
Syndromes vs Side Effects of Treatment
On forums where most people have a diagnosis and are undergoing treatment, there is regular discussion and Q&As about the source of symptoms, i.e. are they a result of a functioning syndrome (i.e. a consequence of the cancer) or something else? For example, some people complain they still have (so-called) carcinoidsyndrome diarrhea after bowel surgery………that needs some careful thought and understanding before coming to what might just be the wrong conclusion, particularly if all tumour markers are normal. I have lost count of the number of times someone has asked about a symptom on a forum and got 50 different answers. One of the reasons why forums can be good at frightening rather than frighteningly good. Personally, I never compare myself to strangers on the internet. I just hope most people are using the forums as ‘sounding boards’ and are simultaneously addressing these very complex issues with their doctors when they are genuinely concerned.
I really feel for anyone who is going through a difficult diagnosisor has been diagnosed and then continues to have numerous problems after initial treatment. I also have a little bit of sympathy for primary care medical staff on the basis this is just one of over 200 types of cancer, many of which have wide age groupings adding to the complexity and difficulty. Moreover, many of the symptoms experienced by NET patients on analysis look very similar to everyday illnesses and other ailments. And if that wasn’t demanding enough for doctors, many patients present with already established and diagnosed comorbidities (other illnesses) which add another level of complexity. These difficulties can then continue throughout treatment. It can be a real challenge and I’m sure even Doctors can be totally flummoxed on occasion by patient presentations.
It is extremely difficult to “sort out the symptoms” when faced with multiple locations/tumour sub-types, multiple treatments causing multiple side effects, multiple side effects causing multiple symptoms, multiple comorbidities with symptoms similar to cancer syndromes and treatment side effects (and vice versa). This disease can be very individual and what happens to one might not happen to another. Although we hope doctors generally take a holistic view when treating NET patients, I have a view that sometimes focussing in on a particular symptom might occasionally be a more effective route (the bottom-up approach – pun not intended!). When eating an elephant, take one bite at a time! It’s useful to know about the range of tumor markers and hormone markers – read more here.
One thing I have learned ……educate yourself to the best of your abilities. This will help you to better advocate for yourself. Improvements are possible.
Neuroendocrine Cancer is a very difficult jigsaw and you sometimes need to look very hard for the missing piece! The ‘missing piece’ can be variable and very individual, i.e. a NET specialist, access to a particular treatment or even just more support or access to support information that works.
The internet is full of blogs and articles about a subject which is described as ‘scanxiety‘ – the joining of the words ‘scan’ and ‘anxiety’. I also noted some authors using the words ‘scanxiety’ and ‘anxiety’ interchangeably which in my opinion is clearly wrong as by definition it is only an anxiety about scans and I guess incorporates the results of scans. Not that we need separate names – at the end of the day, it’s just anxiety regardless of whether it is waiting on the results of a biopsy, blood test, urine test, or anything else related to an illness. No-one goes around saying ‘blood-testxiety’ or ‘biopsyxiety’. Why scans?
‘Scanxiety’ – I just don’t get it ……or more accurately I just don’t get overly anxious about having a scan or getting the results of a scan. Why? Because testing (scans in particular) is the one thing that’s going to keep me alive for as long as possible. I was diagnosed 8 years ago thanks to the trigger of precautionary tests including a scan. I now live with the knowledge (and I accept this fact) that there are still bits of cancer inside me. If I am not regularly tested, there is a chance I will eventually succumb to a serious or irreversible problem which should have been spotted earlier. Even in the event of ‘not so good news’ following a routine surveillance scan, I still see that as a positive because it means the surveillance regime has worked and an investigation can be commenced to more accurately localise and treat the problem. Even if you are in the diagnostic phase and a scan is ordered, you need to get right inside that machine and get it over and done with. It just might save your life.
The test results will be what the test results will be and personally I try to save any worry until I know if I have anything to worry about.
Many cancer patients are under surveillance for a long time and are tested regularly. As an incurable cancer patient myself, I sometimes feel like I’m in a perpetual state of testing. I suspect if I was to let anxiety get the better of me, that would simply lead to other complications I just don’t need. I’m not that insensitive to forget that some people do probably get anxious about actually climbing into a scanner, particularly if they are claustrophobic but that is already a recognised anxiety issue rather than so-called scanxiety. I also suspect people will be anxious about their relatives having scans, particularly the first diagnostic one, worse when young ones are involved and I totally get that. Anxiety (as opposed to so called scanxiety) is a pretty natural reaction. However, to control your fears, you need to face them and then try not to let your anxiety filter down to others. I think people naturally and automatically try to do that without thinking.
‘Scanxiety’ – I just don’t get it. As for the 51,600 search results on the internet, I just don’t get that either!
You may find my 7 tips for conquering fear useful – read here.
Thanks for reading
You may also enjoy my article “10 Questions to ask your Doctor” – click here.
So Victoria Derbyshire has breast cancer and has used her ‘workplace’ as a platform to let people know she is a determined survivor. Nothing wrong with that, it’s great cancer awareness for some and inspiration for others (including me). However, reading through various newspaper follow-up articles, blogs and social media comments, I can see criticism by many for producing an over simplified message (see picture below). Although many of us will be wishing it was so, not all cancer is simple!
Take Neuroendocrine Cancer for example. For some, this ‘silent’ cancer can take years to be finally diagnosed whilst the patient is misdiagnosed with other conditions often with debilitating symptoms. Once diagnosed, surgery (if it’s possible) is just one of a number of treatment options and it will often be multiple times. Follow on treatments include an array of biochemical and nuclear options. If the disease is metastatic, which it frequently is due to its years of ‘silence’, then the condition normally becomes incurable and the patient will be treated for the forseeable future, very often with a reduced quality of life. Victoria might not think she had a fight but for many others, this is a particularly apt word – especially those who can never be sure the cancer has gone.
I’m not suggesting that well-known people shouldn’t make their cancer experience public – in fact I’m all for that!
Get well soon Victoria, I really mean that.
Please Share this post for Neuroendocrine Cancer awareness and to help another patient
Neuroendocrine Cancers can sometimes present with one or more vague symptoms which occasionally results in a lengthy diagnostic phase for some. Sure, there can be issues with doctor experience and knowledge that can add to the problem. However, some people do present with multiple vague and confusing symptoms and some people have comorbidities which have similar symptoms. Textbook diagnostics just don’t make sense, sometimes even when the doctor suspects Neuroendocrine Cancer i.e. classic symptoms of ‘something’ but with negative markers for NETs. Clearly those are extreme cases and just like other complex diseases, many diagnoses of Neuroendocrine Cancer can be extremely challenging. Even for an experienced doctor, it can be a difficult jigsaw!
Most types of Neuroendocrine Cancer can be accompanied by a ‘syndrome’ i.e. the tumours are ‘functional’ and this is normally (but not always) associated with metastatic disease. At this point it’s also worthwhile saying that some Neuroendocrine Cancers can be ‘silent’ (non-functional) for years before any symptoms show and it’s normally only when they metastasize, that these clinical syndromes come to life. Ironically, the manifestation of the disease with a syndrome can occasionally turn out to be a life saver albeit the cancer is normally incurable at this stage – but still treatable.
The most common type of Neuroendocrine Cancer can often present as a collection of symptoms known as Carcinoid Syndrome and the most common of these is flushing with approximately 84% frequency. Others symptoms include (but are not limited to) diarrhoea, heart palpitations, stomach cramps and general abdominal pain/discomfort, shortness of breath, wheezing. You can see the scope for confusion and misdiagnosis. You may find my blog on the ‘5 E’s of Carcinoid Syndrome’ useful.
When you look at these general Carcinoid Syndrome symptoms, flushing seems to be the one that stands out as a ‘cardinal sign’ whereas many others are vague and easily confused with common/regular illnesses. However, the flushing is reported to be different from most people’s perceptions of a ‘flush’. The Carcinoid flush is almost always ‘dry’. To quote my ‘amazing yellow book‘ (co-authored by Woltering, Vinik, O’Dorisio et al), “…. a good rule of thumb is if the flushing is wet (accompanied by sweating), it is due to a cause other than Carcinoid”. Dr James Yao, another well known NETs guru also raises this distinction by stating…. “The facial flushing of carcinoid syndrome is usually a dry flushing, and not associated with sweating like other kinds of flushing. The flushing is often a symptom that others notice before patients do. They may not feel it themselves.”
Additionally, from the same source, there appears to be at least two varieties of flushing in Carcinoid Syndrome related to two different anatomical regions of the primary tumour (again a useful guide from my amazing yellow book):
What to Look For in Flushing – Distinguishing Signs and Symptoms
There are two varieties of flushing in carcinoid syndrome:
1. Midgut: The flush usually is faint pink to red in color and involves the face and upper trunk as far as the nipple line. The flush is initially provoked by alcohol and food containing tyramine (e.g., blue cheese, chocolate, aged or cured sausage, red wine). With time, the flush may occur spontaneously and without provocation. It usually lasts only a few minutes and may occur many times per day. It generally does not leave permanent discoloration.
2. Foregut tumors: The flush often is more intense, of longer duration, and purplish in hue. It is frequently followed by telangiectasia and involves not only the upper trunk but may also affect the limbs. The limbs may become acrocyanotic, and the appearance of the nose resembles that of rhinophyma. The skin of the face often thickens, and assumes leonine facies resembling that seen in leprosy and acromegaly.
Another source for flush descriptions comes from a paid article written by well known NET Endocrinologist – Kjell Öberg.
Four different types of flushing have been described in the literature.
Endocrinology: Adult and Pediatric – 7th Edition 2016.
The first type is the diffuse, erythematous flush, usually affecting the face, neck, and upper chest (i.e., normal flushing area). This flush is commonly of short duration, lasting from 1 to 5 minutes, and is related to early stages of malignant midgut NETs.
The second type is violaceous flush, which affects the same areas of the body and has roughly the same time course or sometimes lasts a little longer. These patients also may have facial telangiectasia. This flush is related to the later stages of malignant midgut NETs and is normally not felt by the patients because they have become accustomed to the flushing reaction.
The third type is prolonged flushing, lasting for hours up to several days. It sometimes involves the whole body and is associated with profuse lacrimation, swelling of the salivary glands, hypotension, and facial edema. These symptoms are usually associated with malignant bronchial carcinoids.
Finally, the fourth type of flushing reaction is bright red, patchy flushing, which is seen in patients with chronic atrophic gastritis and ECLomas (derived from enterochromaffin-like cells) of the gastric mucosa with evidence of increased histamine production.
Differential diagnoses for flushing?
The facial flushing associated with NETs should be distinguished from other causes of flushes. The carcinoid syndrome flush is provoked by spicy food, alcohol, and physical and psychological stress, and it is often worse in the morning. Patients with idiopathic flushes usually have a long history of flushing, starting rather early in life and sometimes with a family history without occurrence of a tumor. Menopausal flushes usually involve the whole body and might be related to release of calcitonin gene–related peptide (CGRP) with transient vasodilation, a so-called dry flush. Another type of menopausal symptom is the wet flush, which includes epinephrine-induced sweating. Proposed mediators of flushing in menopause are CGRP, histamine, prostaglandins, serotonin, lysyl-bradykinin, and substance P. Estrogen is known to have an impact on the production and release of different signaling substances such as noradrenaline and β-endorphin. Low estrogen levels cause lower β-endorphin activity, which in turn enhances the release of gonadotropin-releasing hormone (GnRH), which gives rise to high luteinizing hormone (LH)levels. Postmenopausal women in whom a true carcinoid syndrome is developing can tell the difference between the two types of flushes. Sometimes patients with medullary thyroid carcinoma have brief flushes provoked by alcohol. In patients with watery diarrhea, hypokalemia, achlorhydria syndrome (WDHA; vasoactive intestinal peptide [VIP]omas), a purple-red constant flushing of the whole body may develop. This flushing reaction is related to the vasodilator effects of VIP. Flushes seen in mastocytosis are related to release of histamine from mast cell granules. Mastocytosis is a rare disease of mast cell proliferation that occurs both cutaneously and systemically.
So it’s clear from our experts that the flushing symptom has many potential triggers and can be attributed to the secretion of excess hormones associated with Neuroendocrine Tumours. It’s also clear that the symptom is not just associated with carcinoid syndrome. Although many people focus on serotonin as the main culprit, there appears to be significant evidence to suggest that other hormones may be playing a bigger part with this symptom, e.g. histamine (particularly foregut), tachykinins (Substance P), bradykinins, and prostaglandins.
If you study the online forums, there are frequent questions about flushing, particularly from those looking for a diagnosis and are suspecting Carcinoid Syndrome due to a flushing symptom. However…… even flushing cannot always be attributed to a NET, particularly if it’s the only symptom being presented.
This is a very useful table taken from my amazing yellow book which gives the tests required to determine the potential source of a flushing (differential diagnosis). I strongly suspect this is not an exact science (…..is anything in medicine?) but it’s extremely useful. Personally I would have included Rosacea :-). The referenced article “>Endocrinology: Adult and Pediatric – 7th Edition 2016 by Öberg, Grosssman et al, generally agrees with this list but adds WHDA Syndrome (a pNET called VIPoma), food, drugs, ethanol and idiopathic. It also generalises Neurologic disorders (see more below).
Öberg, Grosssman, et al list the following drugs that can cause flushes:
Calcium channel blockers
Öberg, Grosssman, et al list the following foods that can cause flushes:
Öberg, Grosssman, et al also list the following neurologic disorders that can cause flushes:
Spinal cord lesions
Clearly these lists are those that can cause a flush but not everyone will experience this. For example, when I was syndromic with flushing, I never had any issues with hot beverages.
My own experience with flushing brings back some memories and it emphasises something I say a lot – the patient has a big part to play in their own diagnosis. Please check out this 90 second video about how I did not play my part! I was experiencing a mild and innocuous flushing sensation for some months before I was diagnosed with metastatic Neuroendocrine Cancer. Even though I knew it was weird and something I hadn’t experienced before, I totally ignored it. I failed to mention it at any of my routine GP appointments or my annual asthma clinic. I failed to mention it to my specialist who was investigating a GP/PCP diagnosis of Iron Deficiency Anemia/weight loss. After a CT scan, the specialist appeared to be scratching his head ….. at that point he knew I had cancer but he also knew it was unusual. I suddenly mentioned the flushing and ‘bingo’. It was the face of a man who had just found a missing piece of a jigsaw and he correctly predicted the output from my subsequent liver biopsy.
For the next few months, I was keeping my condition private at work but it was sometimes difficult to disguise the flushing. At least one person thought my blood pressure was going up! Fortunately, my flushing disappeared after treatment.
I’ll complete this post with an interesting summary from an online forum post in which I was participating. There was a general discussion about the severity of ‘syndrome symptoms’ including triggers and I was staggered to read that people were experiencing flushing whilst carrying out routine day-to-day tasks. I’m so happy I don’t flush when I eat one square of chocolate (that would be a complete disaster!). The one which caught my attention was the simple act of washing hair. Whilst I initially raised my eyebrows and laughed, it did make me think back to the last flush I experienced (and touch wood it was the last …..). Following my diagnosis, I commenced daily injections of Octreotide. These injections reduced the flushing but it didn’t eliminate it. However, after my ‘debulking’ surgery in Nov 2010, my flushing disappeared. However, I do remember this small flush coming out of nowhere whilst I was recovering in hospital after that surgery. I was cleaning my teeth and I do vividly remember this minor task taking some effort!
I haven’t had a flush since and if this symptom comes back, I’ll know I have a new problem to contend with.
The build up to NET Cancer Day has begun and I can hear hoofbeats becoming louder every day. Is it a horse, is it a zebra etc etc. However, is this aged equine medical adage still applicable as an awareness tool for Neuroendocrine Cancer or should we be looking for something which is more impactful, up to date, more compelling, more likely be taken seriously and attract new audiences?
For those unaware, the term ‘Zebra’ is a North American medical slang for arriving at an ‘exotic’ medical diagnosis when a more commonplace explanation is more likely. The original context of the term was to correctly indicate that the most obvious diagnosis of symptoms is normally correct – i.e. hoofbeats is almost always the sound of a horse.
“When you hear hoofbeats, think zebra” is clearly not practical and pretty dangerous to those who have the obvious diagnoses (i.e. the vast majority). It’s also likely to turn out to be a very expensive way to do business as common things are common (in fact Neuroendocrine Cancer is now much more common that it was 20 years ago…..).
I’m not suggesting those who are destined to be diagnosed with ‘exotic’ diseases should be ignored for the ‘greater good’, I’m saying that hoofbeats are in actual fact normally the sound of horses in both equine and medical terms – thus why the saying was invented in the first place. By the way, Neuroendocrine Cancer has the fastest rising incidence of all cancers on the planet so it’s far from exotic. What I’m also saying is that perhaps we should stop ‘beating up’ and potentially insulting medical staff using a maladjusted version of the hoofbeat analogy in our PR. I’m afraid the use of cartoon zebras looking sanctimoniously down on cartoon doctors is perhaps not the way to win friends and influence the people we need to work with in helping diagnose quicker.
Moreover, we really need to stop dehumanising patients. I think most NET advocate organisations tend to agree with this view as they mostly do not have zebra icons in their own branding i.e. they get it, even though they might not admit it for fear of upsetting the zebra HQ. By the way, if you hear the sound of hoofbeats in Kenya, it’s likely to be a zebra, so should the Kenyan NET organisation ask their doctors to look for horses? Slightly flippant but necessary to make the point that our disease is international and yet certain organisations appear to be aloof by using it as an international slogan when it is just not relevant internationally.
The use of this skewed version of the phrase might be a great ‘rallying cry’ within the NET Cancer community and for some a ‘populist’ Facebook ‘like farming’ scheme but sharing quite ridiculous pictures of animals that will only be shared by patients is NOT real awareness. In fact, and in my opinion, the ancient, outdated and misleading zebra term is fundamentally flawed in a number of ways.
1. Context. Contextually, the zebra represents a term for a diagnosis (i.e. a disease) but the patients are not their diagnosis, they are not their disease – they are humans.
So when someone says “I am a zebra”, they are in effect saying “I am a disease”. If they say “Dear Zebras”, they are saying “Dear Diseases”. Or the cringeworthy “My fellow diseases”
2. Scope. The term is heavily associated with diagnostics i.e. it has a very narrow scope. It does not sit nicely with the increasingly important long-term maintenance of patients – crucial when you consider this is mostly a slow-growing and therefore highly prevalent disease.
3. Confusion. The term ‘Zebra’ is not exclusively used by the Neuroendocrine Cancer community, it can be, and is used by, other conditions which quite often leads to confusion.
4. Relevance. The term is inextricably linked to rare diseases and as we all now know, NETs are no longer rare. Anyone who says that the group of diseases called Neuroendocrine Tumors (or Neuroendocrine Neoplasms to use the correct scientific term) is rare, is clearly out of touch with the latest incidence and prevalence data (….or chooses to ignore for their own agenda).
I’ve made no secret of the fact that I believe we need a paradigm shift in the way we (the Neuroendocrine Cancer community) spread external awareness of this less common type of cancer. I think everyone agrees we need a lot more public awareness of Neuroendocrine Cancer and also that we need some high-profile ‘ambassadors’ (preferably themselves patients) in order to help promote our cause. Yes, money is useful too but in a ‘chicken and egg’ sense, we need a compelling case to attract the funds. We need new audiences outside the ‘bubble’ I think we appear to be trapped inside. The zebra posse sharing zebra pictures between each other is not efficient awareness.
Here’s my beef. If you speak to any primary or secondary care doctor, you’ll find they are very well aware of the conundrum when faced with a patient who presents with vague and odd symptoms and negative tests. Almost all will say they don’t need reminding that it might be an oddity, and that it is difficult to diagnose. They will definitely accept that some conditions are more difficult to diagnose than others and if you think about the fact that there are over 200 different types of cancer and literally thousands of conditions out there, you can see they have a really difficult job.
Let’s be realistic, very few people are going to be diagnosed with Neuroendocrine Cancer at their very first visit to a doctor. The same could be said for many cancers and many other illnesses. Many conditions are difficult to diagnose and many are misdiagnosed for other things – yes this happens with NETs too. NETs are not as special in these areas as some people make out. Whilst we’re on that subject, please don’t quote patient surveys to me, they are also fundamentally flawed both in terms of numbers of participants and the source of the participants. It amazes me that the NET community uses this flawed (and outdated) information annually including alongside animal antics which degrades what limited value they already have.
I also know that many people (including medical staff and patients) are both confused and incredulous at the NET communities failure to ditch this out of date and single issue awareness message. Some avoid the use of these animal gimmicks and then lapse their real beliefs on 10 Nov just to appear to fit in. However, that’s rather transparent and so people see right through it, like me they want these progressive organisations to stick to their principles. They tell me they don’t like the zebra model but then say a different thing to Zebra HQ.
To quote one famous NET Specialist “….zebras …. we’re beyond that now”
We need our awareness to cover the whole spectrum of being diagnosed and then living with Neuroendocrine Cancer. We share so many issues with many cancer patients in the challenges of living with a long-term condition. This is not special, not unique, and it certainly isn’t a rare occurrence. Key facts continually missed and continually ignored by the ‘zebra posse’ (perhaps intentionally), is that this disease of ours is no longer rare and diagnosis is improving, both of which are now well documented. The ‘zebra posse’ will ensure that quite ridiculous pictures of zebras, zebra patterned clothing and jewelry all take precedence over genuine patient concerns on Facebook forums, i.e. it is hindering proper support for NET patients – NET patients are suffering because of this infatuation.
As one well known NET patient said, “unfortunately the community has become too cute with the icon”.
He’s right, it is really holding us back. It’s a PR disaster.
I’m sure that earlier access to diagnostic testing (scanning in particular) will lead to earlier diagnosis, in fact access to better scans is cited in the lasts SEER NET report as a factor resulting in increased incidence rates. That’s a resource/process issue rather than just a training/knowledge one. We need to work with doctors, not shoot them down for not knowing every minute fact about medicine. NET Cancer is much more likely to be diagnosed at secondary care and we should be equally or even more focused at that level.
If your Doctors don’t suspect something, they won’t detect anything is a more practical and realistic phrase than the impossible and impractical one in current use by our community. Additionally, to suggest that NET Cancer always presents with years of vague symptoms and requires several visits to a physician before a proper diagnosis is simply not true and is a myth. To suggest that an international patient survey of 5000 accurately represents the experience of hundreds of thousands of NET patients out there is way off beam, particularly when the source of the survey patient cohort is taken from those affected most, those with the biggest issues. Big Facebook forums do not represent the average experience of a NET patient.
Finally, I think the patient has a big part to play in diagnosis. Thanks to the internet and the stellar rise of social media, many patients are now much more savvy and are presenting to doctors and specialists with lists of their symptoms and a diary. Some will even have already compiled a list of questions to ask and have their own suggestions about what might be wrong with them. I see undiagnosed patients every day on my social media very clued up, thanks the rise of the online world, and I guarantee you they are (indirectly) educating their first line medical staff when they reel off NET facts. Add in better diagnostic testing and greater access to it (including via primary care), then I think there are positive times ahead for the earlier diagnosis of Neuroendocrine Cancer. You might say it’s a bit of a dark horse.
To summarise ….. The first word of this post is “Opinion” but it is a pretty strong opinion as you would have gathered from the flow of the text. Everyone does indeed have a story and you only tend to hear the bad stories on NET patient forums. Additionally, newspapers love a bad story – they never print “cancer patient quickly diagnosed and treated for cancer – the end”. It’s a bit like in NET world, where the worst cases will be the majority constituents of any forum, because they are looking for help and support. The biggest US forum has around 4000 people but there are over 200,000 people living with NETs in USA (i.e. not rare). There’s a similar quota in UK. I really believe the bad experiences you regularly see on NET forums are the extreme cases (the minority). Unfortunately, most NET patient surveys are taken from these patients so the statistics are totally skewed, presenting a false picture of reality. That’s not to say we ignore this section of the community but we owe them a much better campaigning tool than the now outdated, unfashionable and very inward looking animal analogy.
Let’s move into the 21st century and get on with that.
Thanks for reading
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