The NET Effect

With Neuroendocrine Cancer patients, the mention of “diarrhea“ is a topical subject.  There’s the usual claim that it’s caused by carcinoid syndrome and for some that will be true, particularly people who have tumours associated with that syndrome, that is, those who have mostly a midgut primary; and that is, those who mostly have elevated levels of serotonin (via 5HIAA testing).  When you look at epidemiology data, it becomes clear the numbers associated with carcinoid syndrome are much lower than what might be perceived when analysing many comments in any patient group – most epidemiological data suggests around 10% of the total number of NET cases.

There are a number of reasons for this confusion including the belief that any type of Neuroendocrine Cancer can get carcinoid syndrome when in fact this is way off-beam.  There are several other types of NET and other NET syndromes that also have diarrhea as a listed symptom (read more here). I often wonder if this is partly due to our impaired awareness initiatives at the international and national level that drives people to believe this. I’m also slightly suspicious that patients are being told the ‘easy answer’ in appointments with physicians. The use of the outdated and misnomer term “carcinoid” does not help either. There are many reasons why a Neuroendocrine Cancer patient can get diarrhea and it’s not all about serotonin and (so-called) carcinoid syndrome.

The differential diagnosis of diarrhea in a NET patient is potentially an extensive list of possibilities but in this article, I wanted to focus on the area of bile system impairment which leads to a form of malabsorption causing diarrhea and/or steatorrhea.  This is a piece of the diarrhea jigsaw but is an under-reported or at least an under-discussed problem within the community.

So, I guess I’m focusing on tumours where there has been some sort of small bowel resection and/or gallbladder removal (although other resections may be involved or contributing).  I remember one question in a patient group along these lines “my recent surgery and administration of somatostatin analogues have not improved my carcinoid syndrome; I still have diarrhea” ……. cue a long and difficult explanation. They’re difficult answers mainly because of two things, firstly it’s a complex scenario, and secondly because it isn’t an exact science.  But I’ll try to at least give you some food for thought if you think this might apply to you.  At the very least I hope to give you some tools in order to have a fairly sensible conversation with your doctors and nurses (and dietitians where applicable). 

Does the length of small intestine resection make a difference?

Short answer – yes.  The length of the small intestine removed may produce both problems (diarrhea and steatorrhea).  e.g. Large ileal resections (>100 cm) can lead to luminal bile salt deficiency resulting in fat malabsorption and colonic secretion caused by hydroxy fatty acids. Shorter ileal resections (< 100 cm) may cause diarrhea as a result of stimulation of colonic secretion by unabsorbed bile salts. By binding intestinal bile salts, oral cholestyramine (4 g four times a day) may control this type of diarrhea. The fat malabsorption caused by longer ileal resections may react to pancreatic enzyme replacement therapy (PERT) e.g. creon, nutrizym etc.  It is also thought that somatostatin analogues could potentially exacerbate fat malabsorption as they are known to inhibit digestive enzymes.  Although technically fat malabsorption caused by pancreatic enzyme insufficiency is related to fatty acids rather than bile acids.

Patients with mild to moderate bile acid malabsorption present with watery diarrhea and generally respond very well to treatment with bile acid binders such as cholestyramine. Patients with more severe bile acid malabsorption have both diarrhea and steatorrhea.