24th July 2023

Diseases of the pancreas

The pancreas is a large organ of the abdominal cavity and is located behind the stomach. It consists of a head, neck, body and tail; the head is located at the inner curvature of the duodenum, and the tail ends adjacent to the spleen.

It has crucial endocrine and exocrine functions – the exocrine function relating to glucose metabolism and the exocrine function to the digestive tract. The focus of this section is predominantly on structural diseases or those with a direct effect on the organ itself. As such, diabetes mellitus is not covered. Further discussion of pancreatic exocrine insufficiency can be found in the Nutrition topic.

Acute pancreatitis 

Acute inflammation of the pancreas. A relatively common disease and one which carries a high mortality risk.

Causes

Gallstones and alcohol excess are the 2 most common causes, accounting for the vast majority of cases. The causes can be summarised by the “I GET SMASHED” mnemonic:

• Idiopathic
• Gallstones
• Ethanol
• Trauma
• Scorpion stings and spider bites
• Mumps or malignancy
• Autoimmune
• Steroids
• Hypertriglyceridaemia and hypercalcaemia
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Drugs

Clinical features

Acute pancreatitis classically presents with sudden onset epigastric pain, which may radiate to the back. The pain may also be more generalised. The pain is often associated with nausea, vomiting, and haemodynamic instability. Patients are not typically jaundiced, acutely (unless associated with obstructive gallstones). Patients will often have a history of gallstones or alcohol excess, which are important risk factors to enquire about from the history.

Examination likely reveals tenderness and guarding in the epigastrium. Patients may be peritonitic. Important signs of haemorrhagic pancreatitis (a life-threatening complication) include Cullen’s sign (periumbilical bruising) and Grey-Turner’s sign (flank bruising).

Other complications include pseudocysts (usually around 4-6 weeks after onset of acute illness), pancreatic abscesses, fistulae, AKI, acute respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC).

Assessment and diagnosis

Acute pancreatitis is a diagnosis that should be suspected clinically, and management started on that basis.

A raised serum amylase supports the diagnosis, and serum lipase is an even more sensitive marker. It is often associated with deranged LFTs. Imaging is not essential for diagnosis in the first instance, but an ultrasound scan (to demonstrate gallstones), CT, and MRI may be used to confirm – with a CT abdomen being considered the gold standard, as it can also assess for other causes of acute abdominal pain. If the cause is unknown, further modalities include magnetic resonance cholangiopancreatography (MRCP).

Classification of severity and risk stratification is important to guiding management. The APACHE II score and Glasgrow-Imrie criteria are two risk stratification tools in common usage.

Management

Management is supportive – including IV analgesia and IV fluids. An ABCDE approach should be initially taken for unstable patients. A nasogastric (NG) tube may also be indicated, as nutritional support. Once the cause is established, and the patient is stable, this should also be treated. Antibiotics are only indicated if there is evidence of an associated infection, rather than routinely.

There is a risk of rapid deterioration; patients with severe illness should be identified using the aforementioned risk tools, and ITU involved early if there is clinical concern.

If due to biliary disease, then ERCP may be used to relieve any obstruction. Surgical management may be indicated if there are complications, such as abscess formation, or necrosis. Patients with biliary causes should also have a cholecystectomy once the acute illness has stabilised.

Chronic pancreatitis 

Chronic pancreatitis refers to irreversible inflammation and/or fibrosis of the pancreas, which generally occurs as a consequence of recurrent acute pancreatitis. Repeated inflammation leads to fibrosis and calcification of the gland.

Clinically, it presents as episodic severe abdominal pain, associated with nausea and vomiting, such as in acute pancreatitis. An affected patient will have a background of previous pancreatitis. The causes are therefore the same as for acute pancreatitis; although most commonly it is patients with a history of alcohol excess who are most at risk of chronic pancreatitis, and it is generally associated with a failure to reduce alcohol intake.

Assessment and diagnosis are similar to acute pancreatitis – and it should be suspected in any patient with a background of the former. CT and MRI can be used to demonstrate the extent of fibrosis and any calcification.

Complications include pancreatitis endocrine insufficiency, and exocrine sufficiency due to the direct damage to islets of Langerhans and acinar cells, respectively. This can therefore lead to diabetes mellitus and malabsorption. Patients with chronic pancreatitis, therefore, may be malnourished.

Management is supportive, including analgesia for episodic flare ups, nutritional support, management of complications, and screening for the aforementioned complications. Patients are also at an increased risk of pancreatic cancer. Simple analgesia should be first started, i.e. paracetamol and NSAIDs, and then escalated to weak and strong opioids, as appropriate.

Crucial is risk reduction, such as alcohol and smoking cessation, and medical management of hypercalcaemia and hypertriglyceridemia.

Pancreatic cancer

Pancreatic cancer is a relatively common malignancy, being in the top 10 for both women and men. It is associated with a poor prognosis – with the 5-year survival rate being as low as 10%. Pancreatic cancers can be highly aggressive and debilitating, meaning prompt diagnosis is essential to improving survival – as it generally presents late, with advanced disease. Approximately 90% are adenocarcinomas arising from the digestive acinar cells, with the rest being non-adenocarcinomas of this cell origin, and a small minority being neuroendocrine tumours, which are associated with a better prognosis.

Causes and risk factors

Demographic risk factors include age (with the 60s being the most common decade of onset), male gender, and Afro-Caribbean ethnicity. The biggest modifiable risk factor for pancreatic cancer is smoking, with obesity and alcohol excess further lifestyle factors.

Pancreatic cancer is also associated with a positive family history, and conditions such as diabetes also increase risk. Pancreatitis is an important risk factor, especially chronic pancreatitis and hereditary pancreatitis.

Clinical features

The most common presenting feature is unexplained weight loss. Tumours at the head of the pancreas are associated with obstructive features – such as jaundice, pale stools, and dark urine – as well as pain and anorexia. Tumours of the body and tail are also associated with pain.

Pain is not necessarily a symptom, however, and hence an important maxim in medicine is that painless jaundice should be treated as suspected cancer until proven otherwise.

Assessment and diagnosis

The diagnostic investigation of choice is a CT scan. If the diagnosis is unclear, PET and endoscopic-guided ultrasound (EUS) scans can be used as further modalities. EUS is also used to obtain histological samples.

If there are features of obstruction, then an ERCP should be done to drain the bile duct.

CT of the chest, abdomen and pelvis, and PET scans, are also used for staging. If there is a suspicion of liver metastases, then an MRI should be performed.

Management

The 2 focuses of management are anti-cancer treatment and supportive care.

Analgesia and nutritional support are key. Although not necessarily a presenting feature for most patients, many will progress to experience severe and debilitating pain, which may require specialist palliative care and pain team input. Strong opioids are often indicated, and a coeliac plexus block is amongst the NICE recommendations for uncontrolled pain. Many individuals will suffer exocrine insufficiency and subsequent malnutrition – artificial feeding may be required, and pancreatic enzyme replacement.

Surgery is the first line treatment for those with resectable disease, with subsequent adjuvant chemotherapy or radiotherapy. Only around 20% of tumours are resectable. For non-resectable disease, there is also a role for palliative chemotherapy, which is the first line treatment for those able to tolerate it.

Obstruction should be relieved with either surgery or ERCP, and biliary stenting may also be indicated.

As mentioned, prognosis is poor, and many cancers are often very advanced at the time of presentation. Therefore, palliative care input is often early on and may lead the patient’s care.

Insulinomas 

Insulinomas are a rare form of pancreatic tumour, deriving from the beta cells of the islets of Langerhans in the pancreas. They are a type of neuroendocrine tumour and are generally benign, although a very small percentage may metastasise.

They are important to be aware of as a cause of hypoglycaemia, especially if severe, refractory, and unrelated to concomitant diabetes mellitus. Common symptoms are those of hypoglycaemia, i.e. sweating, tremor, presyncope and palpitations. More seriously, they can also cause neurological symptoms, such as confusion, behaviour and personality changes, visual disturbances, seizure, and coma.

Diagnosis should be suspected in any patient with symptomatic ‘true’ hypoglycaemia, which is defined by Whipple’s triad as:

• Signs and symptoms of hypoglycaemia
• Blood glucose level of less than or equal to 2.5 mmol/L
• Reversibility of symptoms with glucose administration

A full hypogylcaemia panel should then be done, including glucose, insulin and C-peptide levels. C-peptide is associated with endogenous insulin and hence will be elevated in cases of insulinoma. The prolonged fasting test is often diagnostic. Normally, endogenous insulin is suppressed in hypoglycaemia; if a patient has an insulinoma, then a 72-hour fast will fail to suppress insulin levels. CT and MRI can then be done to localise the site of the tumour.

The first line treatment for resectable tumours is surgery – which often includes removal of part of the pancreas – and the majority of insulinomas may be cured this way. Non-resectable tumours can be managed with the somatostatin analogue octreotide, which works by inhibiting insulin secretion.