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Neuroendocrine Cancer Nutrition Blog 3 – Gut Health


3d render medical illustration of the human digestive system - courtesy of Profbiotics.com

3d render medical illustration of the human digestive system – courtesy of Profbiotics.com

My two most popular posts to date are Nutrition Blogs 1 and 2 so I guess this is a topic you guys like?  Lucky for me I’m pushing at an open door as nutritional issues are one of the biggest challenges affecting most Neuroendocrine Cancer patients.  It is also a key factor in maintaining a decent quality of life.

When I first indicated this series was under construction, a few people got quite excited anticipating me to produce advice on what to eat etc.  However, that was never my intention. What people should or should not eat is such a varied problem (or solution?) and there are already several ‘what to or not to eat’ publications/articles out there aimed at NET patients; some more up to date than others (all I would say is to interpret them carefully). Rather I want to look at what causes the nutritional related issues and to a certain extent, try to work out whether these issues are caused by either treatment or an associated syndrome leaving fellow patients to make up their own minds whether this applies to them or not. However, you may find Blog 4 Food for Thought useful.

The first two blogs were Blog 1 – Vitamin and Mineral Challenges and Blog 2 – Malabsorption.  This particular blog is not as ‘clear cut’ or simple as the first two and I suggest you read Blogs 1 and 2 first if you are not familiar with these issues.  Again I’m grateful to Tara Whyand (NET Specialist Dietician from Royal Free London) for some of the input below.

When I first met my surgeon, I found his favourite word was ‘Gut’.  Like me before diagnosis, many of you will have heard or used the word but in an intentionally non-medical context, e.g.  guts (bravery), ‘gut feeling’ or ‘gut instinct’ (intuition). I’ll return to that theme later but it’s no surprise why some scientists refer to our gut as a ‘second brain’.

I always thought the gut referred to just the ‘belly’ area but in medical parlance, the gut has a much bigger geography.  It is sometimes used interchangeably with the term Gastrointestinal (GI) Tract and stretches from the throat to the anus and is responsible (in the most general terms) for food intake, digestion/absorption,  waste processing and finally waste ejection.  NET patients should be familiar with the terms ‘foregut’, ‘midgut’ and ‘hindgut’ which are sometimes used to define the embryological origin of Neuroendocrine primary tumours, although the boundaries and constituent parts seem to vary from site to site.

This blog is generally about ‘gut health’ but I might stray beyond that at times. However, I must warn you this is an area still under scientific study and investigation. I found a mountain of information out there and it’s all very complex! However, with the help of Tara, I focussed and found a few pieces of information which may be useful to NET Cancer patients.

One of the first pieces of advice I was given after my initial surgery was to take probiotics – to keep up my stocks of ‘good’ bacteria.  I started with the liquid drinks you can buy in most supermarkets and supplemented this by eating bioactive yoghurt.  I didn’t really notice any difference from either but the yoghurt was nice to eat!  Tara Whyand then confirmed this advice when I first met her in 2012 at a NET Patient conference.  In 2013 when I started looking for a new normal, I decided to take a high-grade daily capsule containing 5 billion friendly bacteria.  Within weeks I was noticing a difference in bowel motility although I confess to changing other elements of my lifestyle at the same time (more on that later). Nonetheless, I sense probiotics are helping and I won’t be reducing or stopping them any time soon.  If you look at several NET specific dietician/nutrition presentations, most appear to promote the use of probiotics for NET patients. In addition to Tara, there is a useful NET nutritionist on the NET Research Foundation who recommends probiotics greater than 2 billion to help in tackling diarrhea.  CNETS Canada‘s NET specialist contact also recommends them.

Why might probiotics be important?  One of the terms you find in this complex area is the ‘human gut microbiota’, sometimes known as ‘gut flora’. Our ‘gut’ harbours a complex community of over 100 trillion microbial cells, approx 3% of our body mass!  The human gut microbiota is known to have an influence on every part of our body (including the brain…..) and disruption of this ‘community’ has been linked with several gastrointestinal conditions such as Inflammatory Bowel Disease (IBD) and obesity.

Probiotics can help keep the balance and mix of bacteria stable within the gut which can be affected by many different factors, including antibiotics, aging, illnesses (such as IBD), following infective gastroenteritis and (of interest to NET patients) after cancer treatment or gastrointestinal surgery. {1}  Incidentally, the reference here is authored by Tara Whyand and Professor Martyn Caplin (a Neuroendocrine Tumour expert who also happens to be a Gastroenterologist). Useful reading if you have any of the conditions in the report, had gut surgery or like me you are a total geek 🙂

I’d also like to draw your attention to another interesting area of research into something called Small Intestinal Bacterial Overgrowth (SIBO) which Tara is currently researching. (please note Tara blogs for a commercial organisation so I add this disclaimer – I reference her blogs for their intellectual content rather than any product which is associated with the commercial organisation hosting the blogs. I would also add that her blogs are all evidence based and referenced accordingly)

SIBO is a condition where the small intestine is populated by an abnormal amount and/or types of bacteria. It follows that probiotics may be useful in combatting this.  I found some really interesting statements in one of Tara’s blogs e.g. “……low FODMAP diets are not a long-term solution however as it doesn’t correct the bacterial imbalance and most of the foods to be avoided are healthy. For a longer term solution we need to add bacteria back in – probiotics.{2}.  See also some research on potential issues for people who use Proton Pump Inhibitors (PPI) and take Non-steroidal anti-inflammatory drugs (NSAID’S) including ibuprofen – {3}

So how does SIBO potentially and specifically affect NET patients? It can be caused or exacerbated by abdominal surgery to stomach, duodenum, pancreas or via whipples, small & large intestine, poorly controlled diabetes, the long-term use of omeprazole and lansoprazole (PPIs); and possibly antibiotics.  Symptoms vary for everyone from watery diarrhoea suddenly starting 20 times a day to just bloating and wind in both directions, to nothing at all. Some people also lose weight and there is risk of vitamin and mineral deficiency.

There is a test to check this called the Hydrogen breath test. This test uses lactulose ingestion to measure the hydrogen in the breath. If SIBO is diagnosed, treatment is normally via antibiotics. Interestingly, advice is to leave a 2 hour gap between taking probiotics and antibiotics and a high dose multi-strain probiotic should be applied. There is also an indicative test via blood serum checks. If you have low B12 and high folate (B9), this could also be an indication of SIBO. This should be easy to check as B9 and B12 are normally tested together when either is ordered.  If SIBO is left untreated, bacterial imbalance (dysbiosis) can lead to long-term inflammation and other gastrointestinal problems.

Now all of that is very interesting when you consider some of the day-to-day problems faced by NET patients.  To me, this sounds like another good reason to take regular high strength probiotics, which it would seem, may also be working to resolve an issue which is causing or contributing to diarrhoea. Additionally, good advice on a 2 hour gap between taking antibiotics and probiotics – who knew?

I personally take a 5 billion dosage and am happy to recommend the source offline.  However, there is evidence out there to suggest as long as it has some or all of the following strains that are widely available, they should provide benefit: Lactobaccilus plantarum, Lactobaccilus acidophilus, Lactobaccilus brevis, Bifidobacterium lactis and Bifidobacterium longum.

I researched beyond Tara’s advice and also found numerous mentions of very familiar looking SIBO symptoms which all look like classic NET Cancer problems and IBS.  You will like this link which I found very interesting – particularly the bit about the prevalence of patients who have had an “abdominal surgery” or an “Ileocaecal valve resection”.  I guess that would include many NET patients?  (this is a big article so just focus on table 1 near the beginning).

This blog could have been 10 x longer!  I didn’t even get to the bit about the relationship between the gut and the brain – perhaps another day?

Thanks for reading

Ronny
Disclaimer
My Diagnosis and Treatment History

References:

{1} Review of the Evidence for the Use of Probiotics in Gastrointestinal Disorders – CLICK HERE

{2} Gut Bacteria Reach to Our Intake – CLICK HERE

{3} Acid suppressing drugs and bacterial overgrowth – CLICK HERE

Other useful links which have an association to this blog:

{a} Read a Nutrition Booklet co-authored by Tara – CLICK HERE

{b} Follow Tara on Twitter – CLICK HERE

{c} Watch a video of Tara presenting to a group of NET Patients – CLICK HERE

{d} Now Watch Tara answering the Q&A from patients – I enjoyed this – NET patients are very inquisitive! CLICK HERE

Neuroendocrine…..the little suckers get everywhere!


doctorOne of the key milestones in my awareness campaigns occurred when I featured as a guest blogger for one of the biggest cancer ‘support’ organisations in the world – Macmillan.

The aim of the blog ‘Sorry I’m not in service’ was actually to highlight the consequences of cancer and its treatment which is a new Macmillan Campaign; and to a certain extent to highlight the conflict that can exist between work and cancer (another key Macmillan support area).

However, it was also a fantastic opportunity for me to grab the interest of the general population with the word ‘Neuroendocrine’.  The response was amazing and on twitter it was one of Macmillan’s most retweeted posts over that period.  The Macmillan Facebook post was also very popular and still rising with over 500 likes and over 40 shares so far.

There are some great comments on the post and the one which stuck out most is now the title of this blog! I’ve always thought the ‘anatomy’ factor was a strong awareness message for Neuroendocrine Cancer and I outlined this in a blog I wrote last year entitled ‘The Anatomy of Neuroendocrine Cancer‘.  There are not many cancers which have the anatomical reach of Neuroendocrine Cancer –  the ‘suckers’ can indeed get everywhere!

Although there are common areas for Neuroendocrine Cancer to pop up, there are also many rare locations.  I was therefore both astonished and delighted when the Macmillan Facebook post brought together two people from UK diagnosed with a NET of the nasal cavity.

Why is the potential distribution so wide?  Neuroendocrine cancer is nearly always formed in the diffuse neuroendocrine system, which is made up of neuroendocrine cells found in the respiratory and digestive tracts. The respiratory tract includes the bronchial tubes and lungs. The digestive tract starts at the mouth and ends at the rectum. Neuroendocrine cells are also found in the endocrine glands, such as the adrenal glands, pancreas, thyroid and pituitary. These cells are also found in the ovaries and the testes.  However, these ‘little suckers’ have a propensity to spread (metastasise) and can end up in obscure sites throughout the body.  When you carry out a bit of light research in reputable areas plus taking into account their metastatic tendencies, you end up with a list like this:

Small Intestine

Lung

Pancreas

Appendix

Stomach (gastric NETs)

Large Intestine (Colon)

Rectum

Adrenal Glands

Liver

Gallbladder

Bile Ducts

Kidneys

Spleen

Ovaries

Uterus

Testicles

Prostrate

Seminal Vesicle

Parathyroid

Thyroid

Tongue

Cheek

Larynx

Thorax

Bronchus

Oesophagus

Thymus

Pituitary

Pineal

Brain

Breast

Epicardial

Retro-orbital (eye)

Mesentery (keeps the small intestine in place against the abdominal wall)

Peritoneum (lining of the abdominal cavity)

Retroperitoneum (behind the Peritoneum)

Nasal Cavity

Skin (Merkel cell)

Bones in general

Sacrum – the large, triangular bone at the base of the spine

Lymph Nodes – mainly in the area of the Mesentery, Peritoneum, Retroperitoneum, Chest Wall; but also in distant locations such as axillary (armpit) and supraclavicular (collar bone area)

Did I miss any?  Feel free to add!

I don’t post everything on WordPress so please like my associated Facebook page to keep up to date (click here)

Thanks for listening

Ronny

Disclaimer
My Diagnosis and Treatment History

 

I look well but you should see my insides


insides

“You look well” – thank you, I’ll take that!

I’m sat next to patients waiting on their chemotherapy treatment – the “Chemo Ward” sign above the door gives it away.  I’m here for my 28-day cycle injection of Lanreotide which will hopefully keep my Neuroendocrine Tumours at bay. I look all around, the temporary beds and the waiting room are full and all I can see is people who don’t look as well as I do.  Some have hats or bandanas partly disguising the loss of hair.

No matter how many visits I make, I can’t help feeling out of place on a Cancer ward. I’m not sure why I feel like this; after all, I’ve had some very scary surgery and I’m still being treated after 6½ years. However, this thought doesn’t seem to balance it out – some of these people may also have had surgery and are now having adjuvant (follow on) chemotherapy to get rid of remaining cells. Others could be heading for surgery after their neoadjuvant chemotherapy treatment reduces the tumour bulk.

But isn’t that the same as me having 2 months of somatostatin analogue treatment plus a liver embolization in preparation for my surgery?  Perhaps the same principle but somehow this still doesn’t seem to balance out as some of these guys may have been undergoing palliative treatment to extend life.  But shouldn’t administration of somatostatin analogues be considered palliative in the brave new world of ‘incurable but treatable’?  Or indeed biological therapies such as Everolimus (Afinitor) or Sunitinib (Sutent) or even radionuclide therapies such as PRRT?

I guess there’s just something conspicuous about chemotherapy and its side effects that aligns with most people’s view of a standard cancer treatment regime.  People automatically assume you get chemo for any cancer and I have been asked by one or two people why I’m not getting it!  I must be doing OK as I’ve not had it! 

I think the perceptions of cancer patients can be somewhat stereotyped and people generally expect to see ill and poorly people when they see people with cancer – both at the point of diagnosis and during treatment. That said, some cancers can be as invisible after the treatment as they were before diagnosis.  I have metastatic and incurable Neuroendocrine Cancer but I looked well at diagnosis and I look well today.  That said, I wish all those people I saw today well and hope they all get through their chemo treatment.

I actually love it when someone, having found out I have incurable cancer, says “you look really well”.  I’m not annoyed by that.  I’m glad I look well, I mean, who wants to look unwell?  Just don’t tell me I have a ‘good’ cancer!

I guess most people are just being kind despite any obvious awkwardness.  So I just smile and say thank you. If I’m feeling mischievous, I wink and say “yes, I may look well but you should see my insides”. Sometimes they ask about that which then presents another awareness opportunity 😅

You may also like my blog “Things not to say to a cancer patient”

Thanks for reading

Ronny

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

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Neuroendocrine Cancer Syndromes – Early Signs of a Late Diagnosis


Diagnostic Challenges in NET Cancer (type Carcinoid).  Inner segments are the key symptoms, outer segments are some of the potential misdiagnosis/delayed diagnosis. Graphic courtesy of Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology 2005; 128: 1717-1751

One of the curious things about Neuroendocrine Cancer (NET Cancer) is that it can exhibit one or more vague symptoms collectively known as a ‘syndrome’.  Syndrome is an apt word to describe these complications as the most general meaning in medical terms is “group of symptoms that together are characteristic of a specific disorder or disease”

Most people think of Carcinoid Syndrome when they discuss NET Cancer but there are in actual fact, several associated syndromes depending on the location and type of NET Cancer. Not everyone will have a ‘syndrome’ in addition to their tumours. Take the most common form of NET Cancer as an example – statistics vary from source to source but it is estimated that around a 30-45% of all ‘midgut’ patients will present with metastatic disease and around a third of those (∼10-15% of all midgut) will exhibit Carcinoid Syndrome indicating their tumours are functional (secreting excess hormones, particularly serotonin).  It follows that Carcinoid Syndrome itself is not that common and it could be the same with other types of NET Cancer (even though it can appear more prevalent on forums). In fact a large proportion of Pancreatic NETs are non-functional at diagnosis.

These tumours and associated syndromes are treatable for most but the difficult part can be arriving at a diagnosis. Moreover, without a syndrome, some of these tumours can be silently growing and as they grow slowly, the ‘silence’ can go on for some years. Even with a syndrome, the root cause can remain disguised as the symptoms are similar to many day-to-day illnesses, again the reason for the title of this blog. Curiously, the lack of a syndrome can sometimes lead to an even later presentation and the consequences that arise (i.e. no signs to aid a diagnosis). There can be the odd exception but in general terms, NETs are either functional (with a syndrome) or non-functional (no syndrome).

The ISI Book on Neuroendocrine Tumors 2016 (Woltering et al) confirms there are a number of syndromes associated directly and indirectly with NET Cancer. For example Carcinoid, Gastrinoma, Insulinoma, Somatostatinoma, Glucagonoma, and VIPoma are described as individual syndromes according to their secretory hormones and peptides. The referenced publication expands on this list to aid diagnoses by including common presentations, associated tumour types and locations and the offending secreting hormones. You can see why NET Cancer is a diagnostic challenge!

Major NET Syndromes  – (information mainly taken from the ISI Book on NETs with a cross reference from ENETS Guidelines):

Carcinoid – a syndrome connected with conventional carcinoid locations (small intestine, lung, stomach, appendix etc).  Type 2 Gastric NET can also be associated with Zollinger-Ellinson Syndrome (ZES) see below.

(there’s also a very rare instance of pancreatic tumours (PNETs) producing carcinoid syndrome effects – according to ENETs less than 1% of all ‘carcinoid tumours’)

Insulin – Insulinoma (Whipple’s Triad) – Whipple’s Triad is the classic description of insulinoma which includes symptoms of hypoglycemia with a low blood glucose concentration relieved by the ingestion of glucose. These tumours can be located anywhere within the pancreas in the cells that make insulin. Insulin is a hormone that controls the amount of  glucose (sugar) in the blood. It moves glucose into the cells, where it can be used by the body for energy. Insulinomas are usually slow-growing tumors that rarely spread. Some of these tumours will be associated with MEN1.

Gastrin – Gastrinoma  A tumour that forms in cells that make gastrin. Gastrin is a hormone that causes the stomach to release an acid that helps digest food. Both gastrin and stomach acid are increased by gastrinomas. When increased stomach acid, stomach ulcers and diarrhea are caused by a tumour that makes gastrin, it is called Zollinger-Ellinson Syndrome (see also below).  Gastrinoma usually forms in the head of the pancreas. Some of these tumours may be associated with MEN1 syndrome.

GlucagonGlucagonoma.  A tumour that forms in cells that make make glucagon. Glucagon is a hormone that increases the amount of glucose in the blood. It causes the liver to break down glycogen. Too much glucagon causes hyperglycemia (high blood sugar). A glucagonoma usually forms in the tail of the pancreas.  Some of these tumours may be associated with MEN1 syndrome.  See also Sweet’s Syndrome below.

Pancreatic Polypeptide (PP)PPoma.  A complicated one and not too much information (even in the ISI book). However, it’s the third most common type of islet cell tumour (i.e. pNET).  The function of pancreatic polypeptide is not completely understood. Patients present with weight loss, jaundice, and abdominal pain. The diagnosis is confirmed by pancreatic polypeptide levels > 300 pg/ml. Some of these tumours may be associated with MEN1 syndrome.

Vasoactive Intestinal Peptide (VIP) – VIPoma –  Sometimes the syndrome is referred as WDHA – Watery Diarrhea, Hypokalemia (potassium deficiency), and Achlorhydria (absence of hydrochloric acid in gastric secretions).  Also known as Werner-Morrison Syndrome or Pancreatic Cholera.

SomatostatinSomatostatinoma is a very rare NET, with an incidence of one in 40 million persons. These tumours arise from the delta cells in the pancreas, although these cells can also be present in duodenal tissue where around 40% of these tumours occur. Somatostatin is a naturally occurring peptide that inhibits the function of almost all gut hormones (author’s note – this should give you an appreciation of how somatostatin analogues tackle associated syndromes but gives you certain side effects as a result!)

Hedinger Syndrome – the technical term for Carcinoid Heart Disease.

MEN1 – Mainly involved the 3 Ps, Pituitary, Pancreas and Parathyroid.  The pituitary tumours are primarily Prolactinomas, the pancreatic tumours are mainly PPomas, Gastrinomas and Insulinoma.  Many also have association with Zollinger-Ellinson  syndrome (ZES). Read more here.  Previously known as Wermer Syndrome.

MEN2 (A & B) – including association with Medullary Thyroid Cancer (MTC) (including the familial type FMTC) and Pheochromocytoma/Paraganglioma and  Parathyroid hyperplasia.  Read more here.

Von Hippel-Lindau (VHL) – not an exclusively NET syndrome. VHL is a rare disorder caused by a faulty gene. It is named after the two doctors who first described the disease, and affects about one in 35,000 people. Tumours develop in one or more parts of the body. Many of these tumours involve the abnormal growth of blood vessels in parts of the body which are particularly rich in blood vessels. Areas most frequently affected are the eyes, the back of the brain (cerebellum), the spinal cord, the kidneys, the adrenal glands and the pancreas. People are affected differently, even within the same family. The only VHL tumour which tends to run in families affects the adrenal glands (Pheochromocytoma).
Different VHL features tend to develop at different ages. The eye angiomas often develop in childhood. Others, including tumours found in the cerebellum, spinal cord or adrenal glands (Haemangioblastomas and Pheochromocytomas) can develop from late childhood onwards. The kidney tumours are usually the last things that develop, from the mid-twenties onwards.  Most VHL related tumours are benign,

Zollinger-Ellinson Syndrome (ZES).  This is a condition in which one or more tumours form in the pancreas, the upper part of the duodenum or the stomach.  These tumours secrete large amounts of the hormone gastrin, which causes your stomach to produce too much acid. The excess acid can lead to peptic ulcers, in addition to diarrhea and other symptoms.  Associated with Gastrinoma (pNET) and Type 2 Gastric NETs.

Cushing’s – also known as hypercortisolism.  A collection of symptoms caused by very high levels of a hormone called cortisol in the bodyAssociated with AdrenoCorticoTropic Hormone (ACTH).  In Cushing’s disease, oversecretion of pituitary ACTH induces bilateral adrenal hyperplasia. This results in excess production of cortisol, adrenal androgens, and 11-deoxycorticosterone. Cushing’s disease, a subset of Cushing’s syndrome, is due to a pituitary corticotroph adenoma and results in a partial resistance to the suppression of ACTH by cortisol so that secretion is unrestrained. In contrast, causes of Cushing’s syndrome may include the following:

•   Adrenal adenoma or carcinoma arise spontaneously. ACTH levels are undetectable.

•   Non-pituitary (ectopic) tumours produce ACTH. They most frequently originate in the thorax and are highly aggressive small cell carcinomas of the lung or slow- growing bronchial or thymic carcinoid tumours. Some produce corticotropin- releasing hormone (CRH) instead, which stimulates pituitary ACTH secretion and can therefore mimic a pituitary tumour.

•   Other causes include carcinoid tumours of the gastric, pancreatic, and intestinal organs; Pheochromocytomas, and MCT.

The hallmark of Cushing’s syndrome is that ACTH levels are partially resistant to suppression with dexamethasone, even at very high doses.  Some MEN patients with pituitary tumours may have Cushing’s Syndrome.

ACTHoma is essentially the pancreatic tumour version related to Cushing’s Syndrome.

Sweet’s – Dermatitis/rash associated with Glucagonomas.  Not to be confused with Pellagra.

There are many other less known syndromes that appear to be directly or indirectly connected with Neuroendocrine Tumours and I may update this blog if I discover they are more prevalent than I think.

As for my own experience of syndromes, I did once show symptoms of the most common NET syndrome (currently known as Carcinoid syndrome) where the key symptoms are flushing, diarrhea and wheezing.  You can see why those symptoms are frequently and easily confused with other conditions. If you have a similar diagnosis, you may benefit from looking at something known as The 5 E’s which is a useful list of things to be wary of.

I’m certain that I’m now ‘syndrome free’ but I did suffer for a year in 2010 leading up to diagnosis and until my treatment was underway.  I was experiencing flushing and infrequent bouts of diarrhea but I totally ignored it (well, I am a man!). However, it ended up being instrumental in my diagnosis albeit some good luck was involved in getting to that point.  My twist of fate which involved a low hemoglobin score led me to a scan and ‘bingo’.  I had a ‘gastrointestinal blip’ some 18 months previously but that proved colonoscopy negative.  When I read about the experiences of other people who suffer much worse than I ever did, I know I got off lightly despite my distant and metastatic tumour disposition and seemingly late diagnosis.  However, my treatment played and continues to play its part.

For many, the vague and routine symptoms generated by a syndrome contribute to the fact that NET Cancer is frequently misdiagnosed with some people suffering from the side effects for many years before a correct diagnosis is made.

Neuroendocrine Cancer – shh! Can you hear it? 

Thanks for reading

Ronny

Hey Guys, I’m also active on Facebook.  Like my page for even more news.

Disclaimer

My Diagnosis and Treatment History

Most Popular Posts

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

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