NEUROENDOCRINE CANCER OF THE
Neuroendocrine Neoplasm (NENs) is an umbrella term used to cover a group of cancers that start in neuroendocrine cells. These cancers may also be referred to as NETs, NECs, or even Carcinoids. NENs occur when neuroendocrine cells stop working normally and start to grow or behave abnormally.
There are 2 key types of NEN:
- NETs (neuroendocrine tumours) are called ‘well-differentiated’ and may be Grade 1, 2 or 3 (slow to rapid growth rate).
- NECs (neuroendocrine carcinomas) – are called ‘poorly differentiated’ and are usually Grade 3 (rapid growth rate.
To simplify, we use the term NENs throughout this page.
Stomach NENs are rare and account for less than 2% of all stomach cancers. Of those that occur, there are 3 key types – potentially 4*:
Type 1: The most common (70-80%) is usually quite small (less than 10mm) and may be multiple, it is rarely aggressive, usually well differentiated and unlikely to spread to other parts of the body (metastasise). May be associated with Atrophic and / or Auto-immune Gastritis and / or H.Pylori infection.
Type II: Approximately 7-10%, as in Type I it is usually small and multiple, usually slow to grow, well-differentiated and unlikely to spread but the possibility is higher than with Type 1. May be associated with Zollinger Ellison Syndrome (ZES) and / or MEN1
Type III: approximately 20%, usually a solitary, larger lesion than seen in Types I & II (2 or more centimetres). It has well- or poorly differentiated cells, grows more rapidly than Type I or II and is more likely to spread (metastasise).
*Some experts suggest formally sub-dividing Type III according to cancer cell differentiation – i.e. well or poorly differentiated.
Not all cancers are the same or behave in the same way. Some may grow very slowly, may not have invaded nearby structures, or spread to other parts of the body at the time of diagnosis – but they have the potential to. However some may have already spread at the time of diagnosis.
The grade is the rate at which the NEN grows. You might see this referred to as ‘Ki67’ or ‘Mitotic Index’ mentioned in your clinic letters or medical reports. Grade 1 is slow-growing through to Grade 3, a more aggressive, rapidly growing disease.
Causes and potential risk factors for Neuroendocrine Cancer
We do not know exactly what causes Neuroendocrine Cancer – however, it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Factors that may increase the risk of any type of Stomach Cancer include:
- Long-term infection with Helicobacter pylori (H. pylori)
- Long-term, severe acid reflux, gastritis or a condition called pernicious anaemia, which effects your immune system
have a brother, sister or parent who had stomach cancer
- Excess alcohol
- Environmental – such as working in conditions where you may be exposed to certain chemicals, such as in the rubber industry or coal mining
In Neuroendocrine Cancer of the Stomach – certain health conditions have been identified that may be associated with or linked to the development of Type I and Type II. These include:
- Type I – Atrophic and / or Auto-immune Gastritis
- Type II – ZES or MEN1
Most Neuroendocrine Cancers do not run in families; however, a number of rare conditions may increase the risk of them developing. Therefore, if other members of the family have been diagnosed with stomach cancer, or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history but also any family medical illnesses or conditions.
Symptoms that may or may not include Neuroendocrine Cancer associated syndromes
As in other types of Neuroendocrine Cancer, symptoms vary.
In Stomach Neuroendocrine Cancer this variation may depend on Grade and Stage – but also whether there is an underlying / associated cause e.g. Atrophic Gastritis for Type I
There may be no symptoms – or symptoms may include:
- Stomach discomfort / pain
- Reflux – regurgitation, heartburn, dyspepsia – “acid-like” sensation in the stomach and / or food pipe (oesophagus)
- A feeling of fullness in the upper abdomen after eating – even small amounts (early satiety),
- Reduced appetite
- Unintentional weight loss
- Anaemia (low iron and/or B12) – leading to lethargy or severe tiredness
- Stomach and/or duodenal irritation & ulceration – that may lead to either / or
- Nausea and / or vomiting (vomit may or may not contain blood)
Darkening of faeces (poo may be very dark or black).
Type I Stomach NETs tend not to be associated with Neuroendocrine Cancer associated syndromes.
Type II may be associated with ZES and/or MEN1 symptoms.
Type III – if disease has spread to the liver (metastasised) Carcinoid Syndrome may develop, although this occurrence is rare.
Other, rarer symptoms, including Paraneoplastic syndrome and oncological emergencies, (a specific set of health concerns that can occur in any cancer), such as raised calcium levels (Hypercalcaemia), may occur.
Further information about Neuroendocrine Cancer associated and Paraneoplastic Syndromes – including Oncological emergencies – can be found here.
Further information about MEN1 can be found at www.amend.org.uk
Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Stomach:
- Type I: Often associated with low vitamin B12, Anti-parietal cell and anti-intrinsic factor antibodies. Gastric pH may be high (>4)
- Type II: Is associated with Zollinger-Ellison syndrome and Gastrinomas, often as part of MEN1. Vitamin B12 may be normal, iron deficiency is common, anti-parietal cell antibodies may be negative, gastrin (off PPIs) is high but gastric pH may be low (<2)
- Type III: Is not typically associated with high gastrin, despite presence of ulceration.
Bloods and / or urine:
Full blood count
B12 (+ serum Iron)
Parietal cell and intrinsic factor antibodies
Liver and kidney function
Chromogranin A (and B)
Genetic analysis is recommended in case of suspected MEN-1
Scans and other tests:
Upper endoscopy – OGD +/- biopsy
Endoscopic Ultrasound (EUS) +/- biopsy
CT or MRI – for type III
Octreotide (SPECT) scan or Gallium-Dotatate PET/CT : type II and III
FDG-PET – if High Grade / rapidly progressing disease.
Pathology (what can be seen through special tests under a microscope):
Differentiation and cellular morphology
Haematoxylin and oesin
Expert recommendation in Type 1 disease – to also biopsy background mucosa for evidence of dysplasia.
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you.
Treatment options will depend on the type, position and size of your cancer – and whether (and to where) it has spread.
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
- Control of your disease, by slowing or stopping further growth and / or spread
- Palliation, or easing, of any symptoms you may be experiencing.
Monitoring through clinic review, bloods and scans, can be used to assess how well treatment is working or in periods between treatments (which may be months/years). As not everyone will need to be on treatment – surveillance can be used to check your cancer and general health for any signs of change that may mean that a treatment might need to be considered. All treatments have possible side-effects, therefore, it is important to know when treatment may be helpful for you or not.
Will depend on site, size, position and spread of your Neuroendocrine Cancer. Some stomach cancers develop within polyps – others form solid tumours.
A polyp is a small cell clump that develops in 2 ways:
- Pedunculated polyps hang from a short stalk.
- Sessile polyps are flat and they grow directly out of the surrounding tissue.
If your Neuroendocrine Cancer develops within a polyp you may be able to have it removed by:
- Polypectomy – polyps are removed during endoscopy using hot or cold forceps or a snare.
- EndoMucosal Resection (EMR) An endoscope is introduced to the site of the polyp. Using a small needle a fluid is injected underneath to raise the polyp creating a safe field to remove it using a snare. The area is then cauterised (to stop bleeding).
Endocopic Submucosal Dissection (ESD):
The procedure is similar to EMR but uses a small knife, rather than a snare, to remove the polyp, cauterising blood vessels at the same time to prevent bleeding.
If your neuroendocrine cancer can not be removed endoscopically – open surgery may be required:
- Sub-Total or Total Gastrectomy : removes part or all of the stomach through a cut (incision) in the abdomen.
Somatostatin analogues (SSAs):
Can be used to help regulate the secretion of hormones if abnormal levels are being produced. SSAs may also be used to slow down growth rate in low to moderate grade ‘well-differentiated’ neuroendocrine cancer (NET).
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size. This may be the first line therapy in high grade disease – particularly “poorly-differentiated’ NEC or in combination with other treatments. Chemotherapy may also be used to increase tumour cell sensitivity to radiation therapies.
Targeted Molecular Therapies:
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size.
Peptide receptor radionuclide therapy (PRRT):
May also be called Radioligand Therapy – uses targeted radiation to treat neuroendocrine cancer cells. Can be used in some patients who have had a ‘positive’ Octeotide or Gallium scan (‘receptor positive’ disease).
Treatment given via endoscopy – for example, removal of a stomach or rectal polyp.
Through techniques such as embolisation or ablation – can be used to treat Neuroendocrine Cancer that may develop in the the liver and / or lung(s).
Clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy – further information can be found here. Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Managing symptoms, including pain and / or underlying conditions, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
FThere are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
Endoscopic follow-up is recommended for patients with Neuroendocrine Cancer of the Stomach – especially following excision:
- Type I: Conservative management – Lab + clinical control every 6–12 months, as clinically indicated, with OGD + biopsies and/or polyp resection every 12–24 months.
- Type II tumours, endoscopy should be repeated yearly + lab. Polyps <1cm can be managed as per Type I.
- Type III (and IV), after sub-total or total gastrectomy, should follow programs indicated for gastric adenocarcinomas.
- Type III (and IV), inoperable or metastatic, should follow adenocarcinoma protocol as general health, symptoms, treatment options allow.
Advanced disease: follow up as per guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.