Neuroendocrine Tumours of the Liver and Pancreas

Dr Tan Yu-Meng
Director, Consultant General Surgeon

What Are Neuroendocrine Tumours (NETs)?

Neuroendocrine tumours (NETs) are a diverse group of neoplasms arising from neuroendocrine cells, which are distributed throughout the body’s organs and tissues. These cells can produce and secrete hormones into the bloodstream in response to neural signals.

Some NETs grow slowly and are benign, while others may be aggressive and metastasize to other parts of the body. The most common sites for NETs include the gastrointestinal tract, pancreas, and lungs, but they can also be found in the liver, thymus, and other locations.

Pancreatic NETs (pNETs) and gastrointestinal NETs are among the most studied due to their prevalence and the critical functions of the organs involved.

Role of the Liver

The liver is located in the upper right portion of the abdomen, protected by the rib cage. Its primary functions include:


The liver processes and eliminates toxins, drugs, and other harmful substances from the blood, ensuring they are safely excreted from the body.


It is instrumental in the metabolism of fats, proteins, and carbohydrates, converting nutrients from the food we eat into essential blood components, storing vitamins, and supplying cells with energy.

Production of Biochemicals

The liver produces bile, a substance that aids in digestion by emulsifying fats and facilitating their absorption in the intestine. It also produces proteins needed for blood plasma, albumin, and other substances essential for transporting fatty acids.

Regulation of Blood Composition

By regulating blood clotting and removing bacteria from the bloodstream, the liver plays a vital role in maintaining the body’s immune response and preventing infections.

Role of the Pancreas

The pancreas is a vital organ located in the abdomen, nestled between the stomach and the spine. It plays a dual role in the body, functioning both as an endocrine and an exocrine gland:

Exocrine Functions

The majority of the pancreas is composed of exocrine tissue, which produces pancreatic juice containing digestive enzymes. These enzymes are essential for breaking down carbohydrates, proteins, and fats in the intestine, facilitating nutrient absorption.

Endocrine Functions

Scattered throughout the pancreas are clusters of cells known as the islets of Langerhans. These cells are responsible for the organ’s endocrine functions, producing important hormones like insulin and glucagon.

NETs in the Liver and Pancreas

NETs in the liver and pancreas represent a complex subset of neoplasms that arise from neuroendocrine cells present in these organs. These tumours, while relatively rare, are significant due to their potential impact on the body’s hormonal balance and the functions of the liver and pancreas.

NETs in the pancreas, known as pancreatic neuroendocrine tumours (pNETs), originate from the islets of Langerhans. They can produce a variety of hormones, leading to a range of symptoms depending on the type of hormone produced.

Liver NETs can either originate within the liver or represent metastases from NETs located in other parts of the body, most commonly from the gastrointestinal tract.

NETs are classified based on their location, histological features, and the presence of hormone production. They can be categorised into functional and non-functional tumours.

Functional NETs secrete hormones leading to specific clinical syndromes, while non-functional NETs do not produce hormones and may grow unnoticed until they reach a significant size.

The pathophysiology of NETs involves the abnormal growth of neuroendocrine cells, which can proliferate uncontrollably and form tumours.

In the pancreas, this can disrupt the balance of hormone production, leading to hypoglycemia in the case of insulinomas or gastric acid overproduction in gastrinomas. In the liver, NETs can impair liver function, disrupting the liver’s ability to detoxify substances and produce proteins.


Functional NETs

  • Insulinomas (Pancreas): This may lead to episodes of hypoglycemia, characterised by sweating, trembling, dizziness, and even loss of consciousness.
  • Gastrinomas (Pancreas): This can cause peptic ulcers, resulting in abdominal pain, nausea, and gastroesophageal reflux disease (GERD).
  • Carcinoid Tumors (Liver and Gastrointestinal Tract): This may lead to carcinoid syndrome, which includes flushing, diarrhoea, wheezing, and heart valve lesions.

Non-Functional NETs

Symptoms can include abdominal pain, weight loss, jaundice (if the liver is involved), or signs of a mass effect such as nausea and vomiting.


The diagnosis of NETs involves a stepwise approach, including:

  • Clinical Evaluation: A thorough medical history and physical examination, focusing on symptoms suggestive of hormone overproduction or mass effect.
  • Laboratory Tests: Measuring the hormone levels in the blood or urine can suggest the presence of functional NETs. Specific markers, such as chromogranin A, are also used to detect and monitor NETs.
  • Imaging Studies: Ultrasounds, CT scans, and MRIs can provide detailed images of the liver and pancreas, helping to locate and assess the size and spread of tumours.
  • Biopsy: A definitive diagnosis requires a biopsy, where a small sample of the tumour is examined under a microscope to confirm its neuroendocrine nature and to determine the grade of the tumour.

Treatment Options

The main treatment options for NETs include:

Surgical Resection

  • Curative Surgery: If the tumour is localised and operable, surgical removal is often the preferred treatment.
  • Debulking Surgery: In cases where complete removal is not possible, debulking surgery to remove as much of the tumour as possible can help alleviate symptoms.

Medical Therapies

  • Somatostatin Analogues: These drugs can help control symptoms by inhibiting hormone production in functional NETs and may also slow tumour growth.
  • Targeted Therapies: Drugs that target specific pathways involved in tumour growth, such as everolimus and sunitinib, are used especially for advanced pancreatic NETs.
  • Chemotherapy: Generally more effective for fast-growing NETs and used selectively based on the tumour’s characteristics.
  • Peptide Receptor Radionuclide Therapy (PRRT): A targeted treatment that delivers a high dose of radiation directly to cancer cells.
  • Symptomatic Treatment: For functional NETs causing symptoms due to hormone overproduction, additional treatments may be required to manage these symptoms, such as medications to reduce stomach acid for gastrinomas.

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Dr Tan Yu-Meng

Director, Consultant General Surgeon

Dr Tan continues to be one of few surgeons in Asia who perform specialized surgery for peritoneal malignancies in Asia.

  • MBBS (Bachelor of Medicine & Surgery, First Class Honors & Distinction at the University of London) 1994
  • RCSEd (Fellow of the Royal College of Surgeons Edinburgh) 1999
  • Further training in advanced HPB surgery and liver transplantation at the world renowned Liver Unit of Queen Elizabeth Hospital in Birmingham, United Kingdom.
  • Further training in living donor liver transplantation in Japan.

With his interest in gastrointestinal and hepatobiliary-pancreatic (GI-HPB) surgery and the treatment of cancer, Dr Tan joined the department of surgical oncology at the National Cancer Centre in 2003 as a consultant.

Dr Tan’s interest in the management of peritoneal surface malignancies was part of his effort in leading a multidisciplinary team from NCC to Washington Cancer Institute to adopt the techniques and protocols of peritonectomy and HIPEC (Sugarbaker procedure) from Dr Paul Sugarbaker in 2009.

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    Neuroendocrine Tumours of the Liver and Pancreas

    Frequently Asked

    What causes neuroendocrine tumours?

    The exact cause of NETs is not fully understood. Genetic factors, family history of certain syndromes, and other unknown environmental factors may increase the risk of developing these tumours.

    Can neuroendocrine tumours be cured?

    The potential for cure depends on several factors, including the type of NET, its location, whether it has spread to other parts of the body, and the patient’s overall health. Localised tumours that can be completely removed surgically offer the best chance for a cure.

    How is the prognosis for neuroendocrine tumours determined?

    The prognosis for NETs depends on the tumour’s grade (rate of growth), stage (extent of spread), functional status (whether it produces hormones), and the patient’s overall health. Generally, low-grade, localised tumours have a better prognosis than high-grade or metastatic tumours.

    What is the survival rate for neuroendocrine tumours?

    Survival rates vary depending on the type and stage of the NET, its location, and other individual factors. In general, patients with localised, low-grade tumours have a relatively good prognosis, with long-term survival possible. Survival rates decrease for high-grade or extensively metastasized tumours.