What are endocrine pancreatic tumours?
Endocrine pancreatic tumours (EPTs) are a group of tumours derived from certain cells of the pancreas, the Islets of Langerhans. The islet cells in the pancreas produce many different hormones and when these become cancerous, they make too much hormones. EPTs are considered functioing if they are associated with a clinical syndrome due to hormone release or non-functioning if not associated with clinical symptoms due to hormone release. EPTs affects 4 persons per million population per year. There is no difference in incidence between men and women, and the median age at diagnosis is around 53 years. Sporadic EPTs are normally not hereditary, however, in some patients the EPT is a part of an inherited disease such as multiple endocrine neoplasi type 1 (MEN 1) or the von Hippel-Lindau disease. This brochure describes the sporadic EPTs.
What kind of symptoms may EPT cause? How is the diagnosis made, and how is the disease treated?
Symptoms
The clinical symptoms from a functioning EPT depends on which hormone the tumour produces, and according to this the tumours are classified into different groups or syndromes: Gastrinoma or the Zollinger-Ellison syndrome is due to an overproduction of gastrin and may lead to peptide ulcer disease or diarrhoea. Insulinoma is due to insulin overproduction which leads to hypoglycaemia and may result in confusion, palpitation, hunger, pallor and sweating. VIPOMA or the Verner-Morrison syndrome, which is caused by high levels of vasoactive intestinal peptides, may give rise to secretory diarrhoea with hypokalemia, dehydration, weight loss and flush. Glucagonoma is due to glucagon production and may give rise to necrolytic migratory erythema, glucose intolerance, weight loss and anaemia. Somatostatinoma, due to somatoatin production, may lead to diabetes mellitus, cholelithias, diarrhoea and weight loss.
Non-functioning tumours produce inactive hormones and therefore these tumours do not present with any hormonal symptoms. However, the patient can have symptoms caused by the tumour mass, such as pain in the abdomen, loss of weight and jaundice.
Diagnosis
If the tumour is surgically removed, the diagnosis is made through analysis of the removed tumour-mass. Otherwise the initial diagnosis is based primarily on the patient medical history, physical examination, and biochemical tumour markers in blood as well as in urine. To localize the tumour a series of imaging techniques may be employed, computed tomogaraphy (CT), ultrasongaraphy, both from the outside of the body as well as from the inside of the stomach (endoscopic ultrasonography), magnetic resonance imaging (MRI), somatostatin receptor scintigraphy (Octreoscan) and positron emission tomogaraphy (PET). PET is a relatively new method and is still developing, the method has showed a high rate of lesion detection of EPTs.
Treatment
The aims of treatment are to reduce hormone levels, control hormonal symptoms, prevent further tumour growth and possibly also achieve tumour reduction. Whenever possible systematic surgical removal of all resectable tumour is performed. Since the majority of patients have metastasis at the time of diagnosis surgery is not curative and medical treatment has to be added. The causal medical treatment includes mainly chemotherapy, interferon, somatostatin analogues or antisecretory therapy. Chemotherapy is cytotoxic agents that have a checking or stopping effect on cell division. Chemotherapy has effect on all cells in the body but mostly on those that have a rapid division, such as cancer cells. There are a lot of different sorts of chemotherapeutic agents that are used alone or in combinations. Chemotherapy treatment is always given at the hospital.. Interferon is one of the defence mechanisms of the body. Production of interferon is a cellular response to substances such as microbes, tumours and antigens. α-interferon has showed to be effective in midgut carcinoid, and is taken as subcutaneous injections 3-5 times a week. Somatostatin analogues inhibit the release of various peptide hormones, and have proven to be effective in controlling the symptoms of midgut carcinoid tumours. The drug is taken as subcutaneous or intramuscularly injections. Antisecretory therapy is given to inhibit the gastric acid secretion when the hormone gastrin is released from the tumour. These medicines are taken as pills daily.
Other treatment options are embolization, radio frequency ablation and radiotherapy. Embolization means that the hepatic artery is blocked and thereby the tumour cells in the liver depraved of blood supply and die. Radio frequency ablation comprise heating and coagulation of tumour cells in the liver, and this leads to cell death. Radiotherapy is a tumour-targeted radioactive treatment, which means that radioactive labelled substances is used.
Research and future outlook
The research work at the department is ongoing, to improve existing technique for diagnostic and treatment as well as developing new techniques and treatment strategies.
New treatment options are tested in clinical trials. A special interests is directed towards new isotopes for use as tumour-targeted radioactive treatment, substances that affect the angiogenesis in the tumour, and substances that affect receptors at the surface of the tumour cells.
It is important to consider the psychosocial situation for these patients. Research aiming at increasing the knowledge about how patients with midgut carcinoid and their relatives perceive their situation, and how disease and treatment affect these patients quality of life, is in progress.