Supporting the

Neuroendocrine Cancer Community

Pancreas

Pancreas

Further information on the genetic conditions mentioned here can be found at www.amend.org.uk

Further support and information on
Insulinomas can be found at the
Insulinoma Support Network.

Overview

The pancreas is a large gland, that is located behind the stomach and joins the digestive tract via the main pancreatic duct. It has a number of different types of cells that are responsible for producing substances (enzymes, peptides, hormones) that play an essential role in converting the food we eat into fuel for the body’s cells – as well as regulating our blood sugars.

  • Exocrine function – refers to the pancreas’ ability to produce enzymes, that are released into the ducts within the pancreas. These enzymes, mixed with digestive juices, help the body to absorb nutrients, by breaking down the food we have eaten when it reaches the duodenum.
  • Endocrine function – refers to the pancreas’ ability to produce certain gut hormones, such as insulin and glucagon, which are released directly into the bloodstream (rather than through ducts). These gut hormones aid digestion by controlling certain functions of the gut, as well as helping to regulate and control our blood sugar levels.

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.

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 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.

We recommend speaking to your GP, and specialist team, if you have a family history of:

  • MEN1 (Multiple Endocrine Neoplasia 1 – also known as Wermers Syndrome)
  • VHL (Von-Hippel Landau)
  • NF1 (Neurofibromatosis 1)
  • and / or Tuberous Sclerosis.

They may refer you for an NHS genetic test, which will tell you if you have inherited one of the cancer-risk genes – if this has not already been done.

Up to 30% of Neuroendocrine Cancers of Pancreas occur on the background of one of these particular genetic conditions.

Neuroendocrine Cancer of the Pancreas may not be associated with the above mentioned genetic conditions. However, if you do have a genetic condition or strong family history of cancer – knowing this information may help your specialist team in planning your care and ensuring follow up is appropriate for you.

It is therefore vitally important that you are aware of and can tell your specialist team about not only your medical history, but also any family medical illnesses or conditions.

Further information on the genetic conditions mentioned here can be found at www.amend.org.uk

Further support and information on Insulinomas can be found at the Insulinoma Support Network.

Symptoms that may or may not include Neuroendocrine Cancer associated syndromes
(Syndrome is where 2 or more related symptoms occur).

In Pancreatic Neuroendocrine Cancer – you may hear the terms “Functioning” (meaning “with hormone related symptoms”) or “Non-functioning” (meaning “without hormone related symptoms”).

Please note: Functioning or non-functioning may also be terms used to describe whether these cancers show up on nuclear medicine imaging* (see diagnostic tests).

The majority of Neuroendocrine Cancers of the Pancreas are non-functioning, meaning that they do not over produce hormones. Symptoms, if/when they occur, tend to be related to the size and position of the cancer and can include back pain, jaundice, stomach pain and / or weight loss.

Functioning Pancreatic Neuroendocrine Cancers produce syndromes – due to producing too much of a specific gut hormone. These include:

  • Insulinoma (Insulin): dizziness, light-headedness, sweating, hunger, confusion & irritability. Symptoms may get better by eating – so weight gain, rather than weight loss, may also be seen
  • Gastrinoma (Gastrin): Zollinger-Ellison syndrome – acid reflux, heartburn, stomach/chest pain, diarrhoea, low haemoglobin causing tiredness
  • VIPoma (Vasoactive Intestinal Polypeptide): Werner-Morrison syndrome – very watery, frequent and high-volume diarrhoea, with changes in potassium levels in the blood (low potassium) and low levels of acid in the stomach
  • Glucagonoma (Glucagon): NMES – Necrotising Migratory Erythema Syndrome – a skin rash that can spread across the body: It may look like eczema. It may also cause symptoms of diabetes, like feeling tired, going pee a lot, dry mouth, nausea, weight loss and a low hemoglobin . Diarrhoea, blood clots and changes to skin, nails and hair may also be seen.
  • Somatostatinoma (Somatostatin): can cause symptoms of diabetes – like feeling tired, going pee a lot, dry mouth, nausea, weight loss and a low hemoglobin diarrhoea, steatorrhoea (fatty pale stools) and weight loss
  • PPoma (Pancreatic Polypeptide): rarely produces syndrome.

Others Neuroendocrine Cancer associated syndromes – related to the unusual production of non-pancreatic producing hormones (known as ‘ectopic hormone production’) – may include:

  • Cushing’s Syndrome (ACTHoma)
  • Hyperparathyroidism (PTHrPoma)
  • Calcitoninoma (watery diarrhoea and facial flushing)
  • Neurotensinomas (low blood pressure /hypotension, flushing, diarrhoea, unintended weight loss, and diabetes)
  • GRFoma (associated with acromegaly)

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.

Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Pancreas:

Blood and/or urine:

Full blood count
Liver and kidney function
B12/Iron/Ferritin/Folate
Chromogranin A
Urinary or serum 5HiAA (serotonin).
Gut Hormone Profile
Calcium
Calcitonin

 Scans and other tests:

CT chest, abdomen and pelvis and/ or CT chest & MRI abdomen and pelvis
Octreotide (SPECT) or Gallium-Dotatate PET/CT.
FDG-PET
(if available a GLP 1 scan may be beneficial in Insulinoma)

Endoscopic Ultrasound (EUS)

Pathology (what can be seen through special tests under a microscope):

Differentiation and cellular morphology
Synaptophysin
Chromogranin
Ki67
+/- specific hormone staining

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:

  • Surgery
  • Control of your disease, by slowing or stopping further growth and / or spread
  • Palliation, or easing, of any symptoms you may be experiencing.

Surveillance:
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.

Surgery:
To remove or partially remove or bypass the primary pancreatic neuroendocrine cancer and / or secondary sites of disease (metastases). There are several different surgical procedures that may be considered:

Enucleation:
Usually done using keyhole surgery. It is often used for small, slow-growing tumours, like insulinomas. For duodenal tumours this may be done via endoscopic mucosal resection and endoscopic submucosal dissection

Distal pancreatectomy:
Sometimes done using keyhole surgery, this procedure for NET/NEC in the left part of the pancreas (specifically in the body and/ or the tail) involves removing all or part of that side of the pancreas, and possibly the spleen. The spleen may need to be removed if the tail end of the pancreas is attached to the spleen or to prevent complications with the blood flow to the spleen.

Whipples procedure or Pancreatoduodenectomy (aka PPPD):
These procedures are used to treat pancreatic cancers that are found in the head or uncinate process of the pancreas. They may also be used to treat duodenal Neuroendocrine Cancer.

The Whipples procedure is a complex operation that involves removing the right part of the pancreas (the head), along with the end of the bile duct, up to and including the lower part of your stomach, including the pyloric sphincter, part of your small intestine (duodenum) and your gall bladder.

The PPPD procedure is almost the same as a Whipples but does not include removal of the pyloric sphincter.

Total Pancreatectomy:
Involves removing all of the pancreas.

Multi-visceral Pancreatic Resection:
Used to treat large, slow-growing NETs that start in the pancreas but grow into other organs like the stomach, liver, kidney and bowels (Visceral means related to the internal organs, so multi-visceral means involving multiple organs) During the surgery, the tumour and the affected organs are removed together and kept intact. Major blood vessels may require surgical re-routing and / or repair as a result.

Non-surgical treatments:

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).

Chemotherapy:
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).

Radiotherapy:
Is sometimes given after surgery to kill any cancer cells that might remain there. It may also be used for cancer that has spread beyond the primary site, in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain.

Endoscopic procedure:
Treatment given via endoscopy – for example, insertion of a pancreatic stent to bypass an obstruction or narrowing of the pancreatic duct and / or bile duct.

Interventional radiology:
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).

Irreversible electroporation (IRE also known as Nanoknife):
Is a relatively novel therapy, not widely available, that uses a strong electric current to kill cancer cells. It may be particularly useful in treating primary or secondary disease when surgery, or other ablation techniques, are risky because tumours are located too close to structures such as major blood vessels.

Clinical Trials:
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. 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.

Symptom Control:
Managing symptoms, including pain, 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.

There 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.

Non-Functioning:
Follow up is dependent on grading and completeness of resection (if undertaken):

  • G1: complete resection (R0) / no lymph nodes : post operative check and evaluation.
  • G1: incomplete resection (R1/node positive) & G2 : see at 3, 6 and 12 months then annually if stable : labs & CT/MRI.
  • EUS +/- Functional imaging (at 1yr then 3 yearly unless recurrence/ progression is suspected – optional).
  • G3: review 2 – 4 monthly if on ongoing (or may fit criteria) for treatment. FDG-PET as preferred mode of functional imaging in high grade disease.
  • If inherited disorder present/suspected: follow up as per disorder e.g. MEN1, VHL, TS, NF1.

Functioning:

  • G1/G2: 3 – 9 monthly intervals in first 2 years – then at intervals dependent on presence / absence of disease / functionality (see below) – min annual CT + bloods
    (EUS/functional 3 yearly unless recurrence suspected)
  • G3: 2-4 monthly on treatment / potential for treatment

By type:

  • Gastrinoma: Routine + B12, ionised calcium, PTH, Gastrin – with annual assessment for Cushing syndrome
  • Insulinoma: Routine + Fasting glucose, Insulin, C-Peptide, Pro-Insulin, β-hydroxybutyrate
  • Others e.g. VIPoma, PTHRPoma, etc.: Routine + Gut Hormone Profile.
  • If no metastatic disease : 3-6 monthly then annual follow up with specific biomarkers, CT/MRI
  • (EUS/functional 3 yearly unless recurrence suspected).

If metastatic disease present:

  • 3-6 monthly on treatment/ potential for treatment : with specific biomarkers, CT/MRI .
  • (EUS +/- re-biopsy and / or functional imaging in progressive disease).
  • If inherited disorder present/suspected: follow up as per disorder e.g. MEN1, VHL, TS, NF1.

Advanced disease – functioning or non-functioning:

  • 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.

About Us

Neuroendocrine Cancer UK is a UK wide charity solely dedicated to providing support and information to those affected by Neuroendocrine Cancer.

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