I quite like the Facebook memory thing. This morning I got a reminder of a post I made from 7 years ago whilst I was in hospital recovering from my 9 Nov surgery. It had taken 12 days for me to feel strong enough to venture onto social media with a simple message “I’m feeling perkier”. For those not familiar with English localisms, it just means lively, spirited, bright, sunny, cheerful, animated, upbeat, buoyant, bubbly, cheery, bouncy, genial, jaunty, chirpy, sprightly, vivacious, in fine fettle, full of beans, bright-eyed and bushy-tailed. I guess I met some of these descriptors most of the time! I had gotten through the worst and the light at the end of the tunnel was now a faint glimmer.
I’ve recently had a ton of ‘7 years ago cancerversaries’ and there’s still a few to go! I’m currently being reminded of an issue that started just after my initial treatment and by coincidence (perhaps?) the commencement of my Lanreotide (Somatuline Autogel). Itching! However, for me, it’s mainly the right leg below the knee (go figure!). Much less frequently on my arms and sides. I know many people have the same issue but no-one ever seems to find out why – I guess it’s that Neuroendocrine jigsaw thing again?
Initially, I put the issue down to Lanreotide, as this is mentioned in the side effect list on the drug instructions. The initial connection was made because it seemed to be happening immediately after my monthly ‘dart’. A really annoying itch mostly around my ankles and which had to be scratched! An application of a general emollient cream for a few days seemed to do the trick and after a week it was gone (until the next injection …..). However, after a few years, I sensed the issue was drifting away from the injection cycle and adopting a different and more random pattern. I’m also suspicious of a nutritional connection and checking my article Nutrition for NETs -Vitamins and Mineral Challenges, I can see Vit B3 (Niacin) and Vit E are mentioned in regards skin issues. I’d be confused if this was an issue today as I now take plenty supplements to offset GI malabsorption. However, I probably wasn’t taking sufficient between surgery and 2013 as I lacked the knowledge to do so at the time. So nutritional deficiency remains a possibility or at least an added complication. The most recent outbreak has unusually gone on for the last 4 weeks.
I also seem to have had an eczema type issue in my right ear and mild rosacea for more than 7 years (pre diagnosis). As you can imagine my ‘inner detective’ is working overtime! One thing is clear – this itchy leg issue has plagued me for 7 years.
I know that many people have real issues with rashes and skin itching, I’ve seen this so many times with some people describing it as severe. Clearly when this is the case, a doctor’s intervention is generally required. I’ve seen the following connections to NETs and skin issues:
Glucagonoma – a type of functioning pNET can often come with dermatological issues.
Of course there is a Neuroendocrine Carcinoma of the skin known as Merkel Cell Carcinoma – more of a skin lesion effect than regular dermatological issues.
Edit: 2019. Winter in UK has made my itching seem worse, perhaps the cold weather plays a factor. Maybe I just currently have what many people have – dry flaky skin and the onset of winter probably isn’t helping?
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.
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.
Somatostatin Analogues are the ‘workhorse’ treatments for those living with NETs, particularly where certain syndromes are involved. So not just for classic NETs with Carcinoid Syndrome but also for treating insulinoma, gastrinoma, glucagonoma and VIPoma (all types of pNETs) and others. They are most effective if the NETs express somatostatin receptors.
Somatostatin is actually a naturally occurring hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. However, it can only handle the normal release of hormones. When NET syndromes occur, the naturally occurring somatostatin is unable to cope. The word ‘analogue’ in the simplest of terms, means ‘manufactured’ and a somatostatin analogue is made to be able to cope with the excess secretion (in most cases).
Although there is hidden complexity, the concept of the drug is fairly simple. It can inhibit insulin, glucagon, serotonin, VIP, it can slow down bowel motility and increase absorption of fluid from the gut. It also has an inhibitory effect on growth hormone release from the pituitary gland (thus why it’s also used to treat a condition called Acromegaly). You can see why it’s a good treatment for those with NET syndromes, i.e. who suffer from the excess secretions of hormones from their NETs. Clearly there can be side effects as it also inhibits digestive enzymes which can contribute to, or exacerbate, gastro-intestinal malabsorption.
Please note somatostatin analogues are not chemo. There are two major types in use:
Octreotide – or its brand name Sandostatin. It is suffixed by LAR for the ‘long acting release’ version.
Lanreotide – brand name Somatuline (suffixed by ‘Depot’ in North America, ‘Autogel’ elsewhere)
So what’s the difference between the two?
A frequently asked question. Here’s a quick summary:
They are made by two different companies. Novartis manufactures Octreotide and Ipsen manufactures Lanreotide. Octreotide has been around for much longer.
The long-acting versions are made and absorbed very differently. Octreotide has a complex polymer and must be injected in the muscle to absorb properly. Lanreotide instead uses has a novel nanotube structure and is water based (click here to see a video of how this works). It is injected deep-subcutaneously and is therefore easier to absorb and is not greatly impacted if accidentally injected into muscle.
Their delivery systems are mainly via injections but are fundamentally different as you can see from the blog graphic which shows the differences between the long acting release versions. Octreotide long acting requires a pre-mix, whilst Lanreotide comes pre-filled.
The long-acting versions are 60, 90 and 120 mg for Lanreotide and 10, 20 and 30 mg for Octreotide.
Octreotide also has a daily version which is administered subcutaneously.
Octreotide has something called a ‘rescue shot’ which is essentially a top up to tackle breakthrough symptoms. It is a subcutaneous injection.
You can also ‘pump’ Octreotide using a switched on/off continuous infusion subcutaneously.
Other than for lab/trial use, to the best of my knowledge, there is no daily injection, rescue shot or ‘pump’ for Lanreotide that is indicated for patient use.
Whilst both have anti-tumour effects, there are differences in US FDA approval: Octreotide (Sandostatin) is approved for symptom control (not anti-tumor) whereas Lanreotide (Somatuline) is approved for tumour control. However, the US FDA recently added a supplemental approval for syndrome control on the basis that it is proven to reduce the need for short acting somatostatin analogues use – read more here. This supplementary approval followed the ELECT trial – results here.
Always refer to the patient information leaflet as it is not safe to assume that all healthcare professionals are familiar with the administration. Common issues include (but are not limited to): drug temperature requirements, injection site, pinching vs stretching skin, speed of injection.
Here are some interesting videos showing and explaining their administration:
Administering a Somatuline Depot (Lanreotide) injection:
Administering a Sandostatin LAR (Octreotide) injection:
This link also provides guidance on the “new formulation” Octreotide. Click here.
My own experience only includes daily injections of Octreotide (Sep-Nov 2010) and Lanreotide (Dec 2010 onwards). I’ve also had continuous infusion of Octreotide in preparation for surgical or invasive procedures over the period 2010-2012 (i.e. crisis prevention). You can read about my Lanreotide experience by clicking here. If you are interested in what might be coming downstream, please see my blog entitled ‘Somatostatin Analogues and Delivery Systems in the Pipeline’.
Injection site granulomas (lumps)
The issue of ‘granulomas‘ or ‘injection site granulomas’ seems to figure in both drugs. Gluteal injection site granulomas are a very common finding on CT and plain radiographs. They occur as a result of subcutaneous (i.e. intra-lipomatous) rather than intramuscular injection of drugs, which cause localised fat necrosis, scar formation and dystrophic calcification. But no-one seems to know why they occur with somatostatin analogues.
Personally, I find that they are more conspicuous if the injection is done slightly too high which was my initial experience and they took months to fade. I opted to stand up for the first two injections and I attribute this decision for a slightly too high injection site. I now lie down which is actually recommended for the smaller and thinner patient. Although the lumps have reduced in size, I have not seen a new lump for some time indicating location might have been the cause. They sometimes show up on scans. This is not a new problem and has been highlighted for the last 10 years in academic papers. This particular paper is useful and the conclusion confirms this is not something that should worry patients too much. Read more here
Somatostatin Analogues and raised blood sugar levels
It is well documented that both Octreotide and Lanreotide can elevate blood glucose (sugar) levels. Read more in my article Diabetes – the NET Effect.
I think most people have had a form of medical testing at some point in their life, i.e. the sampling and testing of blood, urine, saliva, stool or body tissue. In a nutshell, the medical staff are just measuring the content of a ‘substance’ and then taking a view whether this is normal or not based on pre-determined ranges. These tests are normally done as a physician’s reaction to symptom presentation or maintenance/surveillance of an existing diagnosed condition. Sometimes, abnormal results will lead to more specialist tests.
In cancer, these tests are frequently called ‘markers’. Most tumour markers are made by normal cells as well as by cancer cells; however, they are produced at much higher levels in cancerous conditions. These substances can be found in the blood, urine, stool, tumour tissue, or other tissues or bodily fluids of some patients with cancer. Most tumour markers are proteins. However, more recently, patterns of gene expression and changes to DNA have also begun to be used as tumour markers. Many different tumour markers have been characterized and are in clinical use. Some are associated with only one type of cancer, whereas others are associated with two or more cancer types. No “universal” tumour marker that can detect any type of cancer has been found.
There are some limitations to the use of tumor markers. Sometimes, noncancerous conditions can cause the levels of certain tumor markers to increase. In addition, not everyone with a particular type of cancer will have a higher level of a tumour marker associated with that cancer. Moreover, tumour markers have not been identified for every type of cancer. Tumour markers are not foolproof and other tests and checks are usually needed to learn more about a possible cancer or recurrence.
I’d also like to talk about a group of associated tests, in particular, hormone levels as these tests are really important to help determine the type of Neuroendocrine Tumour. NETs will sometimes oversecrete hormones and this can give clues to the type. The constraints mentioned above apply to hormone levels and other tests to a certain extent.
What this article will not cover
Routine Testing – the post will not cover routine blood tests (i.e. complete blood count etc). Although they may point to a problem, these tests do not necessarily indicate a particular type of NET without other supporting evidence.
Biopsy Testing – Technically, the Immunohistochemical ‘stains’ used in biopsy testing are tumour markers but I’ll not be discussing that today. I did cover the output of biopsies in my blog on NETs – Stages and Grades.
Genetic Testing. This is very specialised but you may find my Genetics and NETs article is of interest.
Sequencing of marker testing – diagnosis
The sequencing of marker testing may have been different for many patients. In my own experience, I had a biopsy and then the biochemical checks were carried out. So regardless of the results of my marker tests, I was to be diagnosed with NETs. Those with lengthy and difficult diagnostic phases will perhaps have had a different sequence with the biochemical markers providing evidence for further tests to formally diagnose. Markers alone will normally not be enough for a diagnosis but they do, however, feed into the treatment plan and provide a baseline at diagnosis and for tracking going forward.
Interpreting test results – International/National/Regional differences
The use of markers tends to be different on an international basis, e.g. specific marker tests can be developed in-country by independent labs. Testing can also vary in the same country as labs through the use of different commercially available ‘testing kits’.
Reference ranges are dependent on many factors, including patient age, gender, sample population, and test method, and numeric test results can have different meanings in different laboratories. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.
Moreover, the ‘normal’ test range can vary from hospital to hospital, even within the same tests. I can only imagine that clinical staff have their own versions of risk thresholds when dealing with test results. Even when results are just above or below, individual physicians can take their own view in a subjective manner. Testing is best done at the same lab each time if possible.
There’s a great website called LabTestsOnlinewhich can describe each test. It’s peer-reviewed, non-commercial and patient-focused but just please note you should always refer to your own lab ‘normal ranges’ which will be printed on your test results. For these reasons, you will not find reference ranges for the majority of tests described on this web site. The link above will take you to the list of ‘country’ affiliated versions with specific information on a country basis.
Here’s some tips I always give people:
1 – Always try to get your own copy of results (preferably on paper) and track them yourself (I use a spreadsheet).
2 – When comparing results inside patient forums, always add the range and if possible, the unit of measurement (i.e. g/L, mmol/L, umol/L etc etc). Failure to do this can at best confuse, and at worst frighten patients. Compare apples with apples not with pears!
3 – Don’t get too excited about rises if the test is still inside the normal range – normal is normal!
4 – Don’t get too excited about rises taking you just outside of normal range – your doctors are looking for bigger spikes.
5. Don’t get too excited about a single test result, your doctors are looking for trends, a single test result is not much to go on.
Although some routine blood markers (complete blood count etc) are useful in NETs, it’s pretty much impossible to cover these in any general detail. I’m going to focus on tumor and hormone associated markers
There are many markers involved with NETs. Some do different jobs and some are just variants measuring the same thing (more or less efficiently). You may also see something called ‘gold standard’ in reference to NET Tumour markers. Although thinking is changing (more on this below) and can vary from country to country, it is generally accepted that Chromogranin A and 5HIAA are the gold standard markers for tumour bulk and tumour functionality respectively. These gold standard tests may not be applicable to every type of NET, particularly 5HIAA. I’m also aware that US doctors are reducing the dependency on CgA and using Pancreastatin instead (although many are measuring both).
NETs are known to be heterogeneous in nature (i.e. consisting of or composed of dissimilarelements;nothaving a uniformqualitythroughout). Whilst some markers can be used widely, it follows that there are many very specialist marker tests for individual types of NET. I think this applies to 3 broad categories of NETs: Tumours known to potentially oversecrete Serotonin and and perhaps others (mainly midgut), Pancreatic NETs (or pNETs) secreting various hormones by type; and other less common types and/or syndromes which might be considered by some to be even more complex than the former two and in some cases there are big overlaps.
Another interesting thing about NET markers is that an undiagnosed patient may undergo several specialist tests to eliminate the many possibilities that are being presented as vague and common symptoms. Sometimes this is necessary to eliminate or ‘home in’ on a tumour type or syndrome/hormone involved (it’s that jigsaw thing again!).
Markers too can be divided into broad categories, those measuring how much tumour is in your body and its growth potential and those measuring how functional (or not) those tumours are. The latter can probably be expanded to measure/assess excess hormone secretion and syndromes.
Certain tests can be anatomy related so to add context and to prevent big repetitive lists when using the terms ‘foregut’, ‘midgut’ and ‘hindgut’, you may find this graphic useful.
Markers for measuring Tumour bulk or load/growth prediction
Chromogranin (plasma/blood test)
Chromogranin is an acidic protein released along with catecholamines from chromaffin cells and nerve terminals. This statement alone might explain why it is a good marker to use with NETs. Depending on the test kit being used, you may see test results for Chromogranin A (CgA) and Chromogranin B (CgB) – the inclusion of CgB tends to be confined to Europe. There is also mention of Chromogranin C (CgC) in places but I’ve never heard of this being used in conjunction with NETs.
One of the disadvantages of CgA is that the results can be skewed by those taking Proton Pump Inhibitors (PPIs). Many NET patients are taking PPIs to treat GERD (….and Zollinger-Ellison Syndrome). In the long-term, this has the result of increasing gastrin levels which can lead to an increase of CgA in the blood including for some months after discontinuing. CgB is said not be as influenced by the use of PPI as CgA. In addition to the issue with PPIs, CgA levels may also be elevated in other illnesses including severe hypertension and renal insufficiency. CgB is also said to be more sensitive to Pheochromocytoma.
Elevated CgA is a constant and somewhat excitable discussion point on patient forums and not just because of the lack of unit of measurement use I discussed above. Some people get quite excited about a single test result. I refer to Dr Woltering et al (ISI Book) where it clearly states that changes in CgA levels of more than 25% over baseline are considered significant and a trend in serial CgA levels over time has been proven to be a useful predictor of tumour growth (i.e. a single test result with an insignificant rise may not be important on its own). Dr Woltering also gives good advice on marker tests when he says “normal is normal” (i.e. an increased result which is still in range is normal).
Here is a nice graphic explaining what else could be the cause of elevated CgA:
CgA appears to be a widely used tumour marker and is effective in most NETs (foregut, midgut and hindgut). It is also sensitive to Pheochromocytoma, particularly when correlated with a 131I-MIBG scan. Interestingly Chromogranin can also be used in the immunohistochemical staining of NET biopsy samples (along with other methods).
As for my own experience, my CgA was only elevated at diagnosis, remained elevated after intestinal surgery but returned to normal after liver surgery (indicating the effect of liver tumour bulk on results). It also spiked out of range when some growth in a distant left axillary node was reported in Jan 2012. Following a lymphadenectomy, it returned to normal again and has remained in range to this day. It has been a good predictor of tumour bulk for me and I’m currently tested every 6 months.
In effect, this marker does the same job as CgA. Interestingly, Pancreastatin is actually a fragment of the CgA molecule. There have been many studies (mainly in the US) indicating this is a more efficient marker than CgA, and not only because it is not influenced by the use of PPI. It has also been suggested that it’s more sensitive than CgA and therefore capable of detecting early increases in tumour burden. It has also been suggested it can be an indication of tumour ‘activity’ (whatever that means). It is widely used in the US and some physicians will use it in preference to CgA (…..although from what I read, CgA also seems to be tested alongside). I’m starting to see this mentioned in the UK.
Neurokinin A (NKA)
This is not a well publicised test. However, it is something used in USA but I’d like to hear from others to validate its use elsewhere. In a nutshell, this test, which only applies to well differentiated midgut NETs, appears to have some prognostic indication. I discovered this test in the ISI NET Guidance and it’s backed up by a study authored by names such as Woltering, O’Dorisio, Vinik, et al. This is not a one-off test but one designed to be taken serially, i.e. a number of consecutive tests. These authors believe that NKA can also aid in the early identification of patients with more aggressive tumors, allowing for better clinical management of these patients. NKA is sometimes called Substance K.
Neuron-Specific Enolase (NSE)
In patients with suspected NET who have no clear elevations in the primary tumor markers used to diagnose these conditions, an elevated serum NSE level supports the clinical suspicion.
Markers for measuring Tumour functionality/hormone/peptide levels
So far, I’ve covered basic tumor markers which have a tumor bulk and/or prognostic indication. This section is a slightly more complex area and many more tests are involved. There’s often a correlation between CgA/Pancreastatin and these type of markers in many patients i.e. a serial high level of CgA might indicate a high level of tumour bulk and therefore increased production of a hormone in patients with a syndrome or oversecreting tumor. However, it frequently does not work out like that, particularly when dealing with non-functioning tumours.
The type of marker for this element of NET diagnosis and surveillance will vary depending on the type of NET and its location (to a certain extent). Like tumour bulk/growth, there might be different options or test variants on an international basis. There are too many to list here, so I’ll only cover the most common.
Serotonin Secreting Tumors
There are a few markers in use for measuring the functionality of this grouping of tumours. This tumour group has a tendency to secrete excess amounts of the hormone Serotoninalthough it differs depending on the area of the primary. For example, hindgut tumours tend to secret lower levels than foregut and midgut and therefore this test may present within range. Please also note there may be other hormones of note involved. The antiquated and misleading term ‘Carcinoid’ is sometimes used as a descriptor for these tumours and more and more NET scientific organisations and specialists are now avoiding use of this term.
5HIAA. 5HIAA is a metabolite of Serotonin thus why it’s a useful thing to measure to assess functionality in this grouping of tumours. 5HIAA is actually the ‘gold standard’ test for functioning serotonin secreting tumours. It’s a key measure of the effects of carcinoid syndrome and the risk of succumbing to carcinoid heart disease. However, there are two methods of testing: Urine and Plasma. The latter is mainly used in USA but other countries are now looking at implementing the plasma version (in fact I’m now tested in both at my local hospital in UK). The rather obvious key difference between the two is practicality. With the 24 hour urine, there are two key issues: 1. The logistics (i.e. lug the jug). 2. Fasting for up to 3 days prior to the test (4 if you count the day of the test). There are numerous variations on the fasting theme but most labs tend to say not to eat at least the following foods that contain high levels of serotonin producing amines: avocados, bananas, chocolate, kiwi fruit, pineapple, plums, tomatoes, and walnuts. Some lists contain additional items. With the plasma version, the fasting period is reduced to 8 hours. There are also medicinal limitations including drugs that can also alter 5-HIAA urine values, such as acetanilide, phenacetin, glyceryl guaiacolate (found in many cough syrups), methocarbamol, and reserpine. Drugs that can decrease urinary 5-HIAA levels include heparin, isoniazid, levodopa, monoamine oxidase inhibitors, methenamine, methyldopa, phenothiazines, and tricyclic antidepressants. Patients should talk to their doctor before decreasing or discontinuing any medications.
As for my own experience, my 5HIAA (urine) was elevated at diagnosis only returning to normal after removal of my primary and commencement of Lanreotide. It has been a good measure of tumour functionality for me and I’m currently tested every 6 months.
Other tests for the tumour subgroup include but not limited to:
Serum Serotonin (5-HydroxyTryptamine; 5-HT). Firstly let’s deconflict between 5HIAA above and the serotonin (5-HT) blood test. 5HIAA is a metabolite of serotonin but the serotonin test is a measure of pure serotonin in the blood. Morning specimens are preferred and this is a fasting test (10-12 hours). There is always debate on forums about Serum Serotonin results. I have Dr Liu on record as saying “a high serotonin level measured in the blood in isolation really isn’t that dangerous. It’s the 5HIAA (a breakdown product of serotonin, which is easily measured in the blood and urine) that is considered to be more indicative of persistent elevated hormone. It’s this test that is most closely related to the carcinoid heart disease”.
Substance P. A substance associated with foregut and midgut tumours. It is a vasoactive protein that can cause wheezing, diarrhea, tachycardia, flushing
Histamines – Usually associated with foregut tumors. Appears to be involved in patchy rashes and flushing. The advice in the ISI NET book is no anti-histamine medication to be taken for 48 hours prior to blood draw.
Gastric NETs (Stomach)
Testing will be different depending on the Type:
Type 1 – Typical Low Grade, tends to be caused by atrophic gastritis.
Type 2 – Atypical Intermediate Grade and tends to be caused by gastrin secreting tumours. Type 2 normally needs a check for MEN1/Zollinger-Ellison Syndrome.
Type 3 – Tend to be larger and more aggressive tumours.
The key makers are CgA and Gastrin although Gastrin may not be elevated in Type 3. Gastrin ph is useful to differentiate between Type 1 and Type 2. 5HIAA can be considered but Carcinoid Syndrome is rare in Gastric NETs.
NETs of the Pancreas (pNETs)
pNETs can be very difficult to diagnose and not only because they share some presentational similarities to their exocrine counterparts. Some pNETs actually comprise tumours arising in the upper part of the duodenum (small intestine) close to the Pancreas. Moreover, more than half of pNETs are non-functional which increases the difficulty in suspecting and then finding the tumours. However, where there is clinical presentation or suspicion, these symptoms can lead to the appropriate testing to support the output of scans. The fasting gut profile mentioned above can be useful in identifying the offending hormones when the type of NET is not yet known.
Gut Hormones (Glucagon, Gastrin, VIP, Somatostatin, Pancreatic Polypeptide)
A gut hormone screen is used for the diagnosis of a variety of endocrine tumours of the pancreas area. Analysis includes gastrin, VIP, somatostatin, pancreatic polypeptide, and glucagon, but there may be others depending on processes used by your ordering specialist or hospital.
1. You may see this referred to as a ‘Fasting Gut Profile’ or a ‘Fasting Gut Hormone Profile’.
2. The individual hormones measured seem to differ between hospital labs.
3. The fasting conditions also vary between hospitals and labs but all agree the conditions are critical to the most accurate results. Always ask for instructions if you’re offered this test.
The gastrin test is usually requested to help detect high levels of gastrin and stomach acid. It is used to help diagnose gastrin-producing tumours called gastrinomas, Zollinger-Ellison (ZE) syndrome, and hyperplasia of G-cells, specialised cells in the stomach that produce gastrin. It may be measured to screen for the presence of multiple endocrine neoplasia type I (MEN) It may be used if a person has abdominal pain, diarrhoea, and recurrent peptic ulcers. A gastrin test may also be requested to look for recurrence of disease following surgical removal of a gastrinoma.
Vasoactive intestinal peptide (VIP) measurement is required for diagnosis of pancreatic tumour or a ganglioneuroma which secretes VIP. Administration of VIP to animals causes hyperglycaemia, inhibition of gastric acid, secretion of pancreatic bicarbonate and of small intestinal juice, and a lowering of systemic blood pressure with skin flush. These features are seen in patients with a tumour of this type which is secreting VIP.
Glucagon is measured for preoperative diagnosis of a glucagon-producing tumour of the pancreas in patients with diabetes and a characteristic skin rash (necrolytic migratory erythema).
Pancreatic polypeptide (PP) production is most commonly associated with tumours producing vasoactive intestinal polypeptide and with carcinoid syndrome and, less commonly, with insulinomas and gastrinomas.
When secreted by endocrine tumours, somatostatin appears to produce symptoms similar to those seen on pharmacological administration, i.e. steatorrhoea, diabetes mellitus and gall stones.
There are several types of pNETs, each with their own syndrome or hormone issue. When they are suspected due to the presentational symptoms, the markers that could be used are listed below. These types of tumours are complex and can be related to one or more syndromes. A patient may be tested using multiple markers to include or exclude these. Depending on other factors, some physicians may recommend additional marker testing in addition to the most common types below.
Somatostatinoma – Somatostatin (plasma somatostatin like immunoreactivity)
PPoma – Pancreatic Polypeptide (PP)
Pheochromocytoma/Paraganglioma – Adrenaline-producing tumours. Plasma and urine catecholamines, plasma free total metanephrines, urine total metanephrines, vanillylmandelic acid (VMA)
Medullary Thyroid Cancer. Medullary thyroid cancer (MTC) starts as a growth of abnormal cancer cells within the thyroid – the parafollicular C cells. In the hereditary form of medullary thyroid cancer (~20% of cases, often called Familial MTC or FMTC), the growth of these cells is due to a mutation in the RET gene which was inherited. This mutated gene may first produce a premalignant condition called C cell hyperplasia. The parafollicular C cells of the thyroid begin to have unregulated growth. In the inherited forms of medullary thyroid cancer, the growing C cells may form a bump or nodule in any portion of the thyroid gland. Unlike papillary and follicular thyroid cancers, which arise from thyroid hormone-producing cells, medullary thyroid cancer originates in the parafollicular cells (also called C cells) of the thyroid. These cancer cells make a different hormone called calcitonin, which has nothing to do with the control of metabolism in the way thyroid hormone does. The other test often seen in MTC is Carcinoembryonic Antigen (CEA). CEA is a protein that is usually found in the blood at a very low level but might rise in certain cancers, such as medullary thyroid cancer. There is no direct relationship between serum calcitonin levels and extent of medullary thyroid cancer. However, trending serum calcitonin and CEA levels can be a useful tool for doctors to consider in determining the pace of change of a patient’s medullary cancer.
[please note there are extremely rare occurrences of elevated calcitonin from places outside the thyroid – read more here.
Parathyroid– Parathyroid hormone (PTH), Serum Calcium. Parathyroid hormone (PTH) is secreted from four parathyroid glands, which are small glands in the neck, located behind the thyroid gland. Parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. A primary problem in the parathyroid glands, producing too much parathyroid hormone causes raised calcium levels in the blood (hypercalcaemia – primary hyperparathyroidism). You may also be offered an additional test called Parathyroid Hormone-Related Peptide (PTHrP). They would probably also measure Serum Calcium in combination with these type of tests. The parathyroid is one of the ‘3 p’ locations often connected to Multiple Endocrine Neoplasia – MEN 1 – see MEN below.
HPA AXIS – It’s important to note something called the HPA axis when discussing pituitary hormones as there is a natural and important connection and rhythm between the Hypothalamus, Pituitary and the Adrenal glands.
Adrenocorticotropic hormone (ACTH) is made in the corticotroph cells of the anterior pituitary gland. It’s production is stimulated by receiving corticotrophin releasing hormone (CRH) from the Hypothalamus. ACTH is secreted in several intermittent pulses during the day into the bloodstream and transported around the body. Like cortisol (see below), levels of ACTH are generally high in the morning when we wake up and fall throughout the day. This is called a diurnal rhythm. Once ACTH reaches the adrenal glands, it binds on to receptors causing the adrenal glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. It also increases production of the chemical compounds that trigger an increase in other hormones such as adrenaline and noradrenaline. If too much is released, The effects of too much ACTH are mainly due to the increase in cortisol levels which result. Higher than normal levels of ACTH may be due to:
Cushing’s disease – this is the most common cause of increased ACTH. It is caused by a tumor in the pituitary gland (PitNET), which produces excess amounts of ACTH. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome). It is likely that a Cortisol test will also be ordered if Cushing’s is suspected.
This is a steroid hormone, one of the glucocorticoids, made in the cortex of the adrenal glands and then released into the blood, which transports it all round the body. Almost every cell contains receptors for cortisol and so cortisol can have lots of different actions depending on which sort of cells it is acting upon. These effects include controlling the body’s blood sugar levels and thus regulating metabolism acting as an anti-inflammatory, influencing memory formation, controlling salt and water balance, influencing blood pressure. Blood levels of cortisol vary dramatically, but generally are high in the morning when we wake up, and then fall throughout the day. This is called a diurnal rhythm. In people who work at night, this pattern is reversed, so the timing of cortisol release is clearly linked to daily activity patterns. In addition, in response to stress, extra cortisol is released to help the body to respond appropriately. Too much cortisol over a prolonged period of time can lead to Cushing’s syndrome. Cortisol oversecretion can be associated with Adrenal Cortical Carcinoma (ACC) which can sometimes be grouped within the NET family.
Other hormones related to ACC include:
Androgens (e.g. Testosterone) – increased facial and body hair, particularly females. Deepened voice in females.
Estrogen – early signs of puberty in children, enlarged breast tissue in males.
Aldosterone – weight gain, high blood pressure.
Adrenal Insufficiency (Addison’s Disease) occurs when the adrenal glands do not produce enough of the hormone cortisol and in some cases, the hormone aldosterone. For this reason, the disease is sometimes called chronic adrenal insufficiency, or hypocortisolism.
A tumour outside the pituitary gland, producing ACTH (also called ectopic ACTH). With NETs, this is normally a pNET, Lung/Bronchial NET or Pheochromocytoma.
Carcinoid Heart Disease(CHD) (Hedinger syndrome)I’m not really talking directly about a tumour here but thought it would be useful to include a blood test called NT-proBNP. I’ve left a link to my CHD article in the paragraph heading for those who wish to learn more about CHD in general. For those not offered an annual Echocardiogram or are ‘non-syndromic’ there is a screening test that can give an indication of any heart issue which might then need further checks.
The Future – Molecular Markers?
This is testing using DNA and genes. Exciting but complex – check out this article which involved some NETs.
Tumour Markers and Hormone levels – complex subject!
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 Neuroendocrine Cancer Treatment
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.
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!
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.
As for my own strategy, I filtered out the advice from a NET specialist dietitian and have managed to make quite a difference to my Quality of Life (QoL) without resorting to really expensive drugs (which come with their own side effects). 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 (still assessing as at April 2018) 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 1.6). 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