Pancreatic Cancer

Pancreatic cancer will typically refer to ductal carcinoma of the pancreas, which comprises up to 90% of primary pancreatic malignancies. The remaining number can be divided into exocrine tumours (such as pancreatic cystic carcinoma) and endocrine tumours (derived from islet cells of the pancreas).

Carcinoma of the pancreas is the 10th most common cancer in the UK, yet its high mortality rate makes it is the 4th most common cause of cancer death. It is rare under 40 years of age, with 80% of cases occurring between 60-80yrs. It is rarely diagnosed early enough for curative treatment.

In this article, we shall look at the risk factors, investigations and management of a patient with pancreatic cancer.


The most common type of pancreatic cancer is ductal carcinoma (90% of primary pancreatic malignancies). Other rarer forms include cystic tumours, ampullary cell tumours and islet cell tumours, which all often have a much better prognosis.

As the cancer spreads, direct invasion of local structures typically involves the spleen, transverse colon, and adrenal glands. Lymphatic metastasis typically involves regional lymph nodes, liver, lungs, and peritoneum. Metastasis is common at the time of diagnosis.

Fig 1 - Pancreatic cancer can spread directly to surrounding structures, such as the spleen, transverse colon and adrenal gland.

Figure 1 – Pancreatic cancer can spread directly to surrounding structures, such as the spleen, transverse colon and adrenal gland.

Risk Factors

There are few clear risk factors for the development of carcinoma of the pancreas. Those that have been identified include smokingchronic pancreatitis, and recent onset of diabetes mellitus. There may also be a hereditary element, as 7% of patients have a family history of the disease.

Late onset diabetes is an additional risk factor. Those diagnosed with diabetes after 50 years of age have an 8 times greater risk of developing pancreatic carcinoma in the following three years than the general population.

Clinical presentation

Approximately 80% of cases of pancreatic carcinoma are unresectable at diagnosis, testament to the late and often vague and non-specific nature of its presentation.

The specific clinical features can depend on the site of the tumour. Cancer affecting the head of the pancreas classically presents with combination of:

  • Obstructive jaundice – due to compression of the common bile duct (present in 90% of cases at time of diagnosis)
  • Abdominal pain (radiating to the back) – due to invasion of the coeliac plexus or secondary to pancreatitis
  • Weight loss – due to the metabolic effects of the cancer, or secondary to exocrine dysfunction

Less common presentations include acute pancreatitis and thrombophlebitis migrans (a recurrent migratory superficial thrombophlebitis, caused by a paraneoplastic hypercoagulable state). Tumours of the tail of the pancreas have an insidious course and not generally symptomatic until a late stage.

On examination, patients may appear cachecticmalnourishedand jaundiced. On palpation, an abdominal mass in the epigastric region may be felt, as well as an enlarged gallbladder (as per Courvoisier’s Law)

Courvoisier’s Law

Courvoisier’s law states that in the presence of jaundice and an enlarged/palpable gallbladder*, malignancy of the biliary tree or pancreas should be strongly suspected as the cause is unlikely to be gallstones. This sign may be present if the obstructing tumour is distal to the cystic duct. In reality an enlarged gallbladder is present in less than 25% of patients with pancreatic cancer.

Differential Diagnosis

Pancreatic cancer often presents with vague, non-specific features. The differential diagnoses are vast and include:

  • Causes of obstructive jaundice – gallstone disease, cholangiocarcinoma, benign gallbladder stricture
  • Causes of epigastric abdominal pain – gallstones, peptic ulcer disease, pancreatitis, abdominal aortic aneurysm (AAA), gastric carcinoma, acute coronary syndrome


Laboratory tests

Any suspected pancreatic cancer should warrant initial blood tests, such as FBC (anaemia or thrombocytopenia) and LFTs (raised bilirubin, alkaline phosphatase, and gamma-GT, showing a obstructive jaundice picture).

CA19-9 is a tumour marker with a high sensitivity and specificity for pancreatic cancer, yet its role is in assessing response to treatment rather than for initial diagnosis.


The initial imaging for pancreatic cancer is commonly an abdominal ultrasound, which may demonstrate a pancreatic mass or a dilated biliary tree (as well as potential hepatic metastases and ascites if very late stage disease).

CT scaning* (Figure 2) is both the most important investigation in terms of diagnosis, but also the most prognostically informative as it can stage disease progression.

Endoscopic ultrasound (EUS) will often subsequently be used to guide fine needle aspiration biopsy in order to histologically evaluate the lesion. ERCP can also be used to access the lesion for biopsy or cytology, if in a suitable location

*A pancreas protocol CT scanning (a contrast CT scan with arterial, pancreatic and portal venous phases) is extremely effective at assessing resectability of a pancreatic mass

Fig 2 - A adenocarcinoma located in the pancreatic head, identified on CT scan

Figure 2 – A adenocarcinoma located in the pancreatic head, identified on CT scan



The only curative management option is currently radical resection. Absolute contraindications for surgery include peritoneal, liver and distant metastases. Morbidity following the procedure is high (up to 40%) and specific complications include formation of a pancreatic fistula (due to leakage of pancreatic juices from the incised margin of the pancreas), delayed gastric emptying, and pancreatic insufficiency.

For patients with tumours of the head of the pancreas, the most common surgery with curative intent is pancreaticoduodenectomy, also known as a Whipple’s procedure*. For patients with tumours of the body or tail of pancreas, a distal pancreatectomy can often be performed, yet the risk of forming a pancreatic fistula remains.

Cochrane review found that pancreatic resection increases survival and reduces costs compared to palliative treatments in patients with locally advanced pancreatic cancer and venous involvement. However, patients should only be selected for this procedure if there is sufficient clinical expertise available and the patient is aware of the potentially increased morbidity associated with the procedure.

*Newer techniques for pancreatic resection include pylorus preservation or SMA/ SMV resection

Whipple’s Procedure

Whipple’s procedure involves the removal of the head of the pancreas, the antrum of the stomach, the 1st and 2nd parts of the duodenum, the common bile duct, and the gallbladder. All viscera removed in the operation are done so due to their common arterial supply (the gastroduodenal artery), shared by the head of the pancreas and the duodenum.

Following this, the tail of the pancreas and the hepatic duct are attached to the jejunum, allowing bile and pancreatic juices to drain into the gut, whilst the stomach is subsequently anastomosed with the jejunum allowing for the passage of food.

Fig 3 - Pancreaticoduodenectomy (Whipple's procedure). A: Pre-procedure, B: Post-procedure.

Fig 3 – Pancreaticoduodenectomy (Whipple’s procedure). A: Pre-procedure, B: Post-procedure.


recent review remarked that the role of chemoradiotherapy is becoming increasingly questioned in locally advanced disease, particularly considering the results of the LAP-07 trial, whilst in metastatic disease the use of FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin) and nab-paclitaxel plus gemcitabine regime have yielded only modest improvements in survival.

Adjuvant chemotherapy, generally with 5-flourouracil, is recommended after surgery as it has been demonstrated to improve survival following the ESPAC-1 trial. ESPAC-1 also demonstrated patients treated with adjuvant chemoradiotherapy had worse outcomes overall than those treated with adjuvant chemotherapy alone.

Palliative Care

The majority of patients with pancreatic cancer are not candidates for curative surgery, but instead require palliative care. Obstructive jaundice and associated pruritis can be relieved with the insertion of a biliary stent, via ERCP or percutaneously.

There is also a role for palliative chemotherapy, with NICE currently suggests a gemcitabine-based regime in patients with a reasonable performance status.

Exocrine insufficiency is common in advanced disease or those who have had significant excision of the pancreas and can lead to malabsorption and steatorrhoea. This can initially be treated with enzyme replacements (including lipases), such as Creon®, which are typically administered with meals.  A recent study showed for those patients undergoing pancreatoduodenectomy for pancreatic cancer, the use of pancreatic enzyme replacement therapy was associated with an improved survival.


Pancreatic cancer has a high metastatic capacity even in small tumours. The prognosis in pancreatic cancer remains dismal, with overall 5-year survival rate is less than 5%. One study showed the prognostic impact of tumour size is restricted only to patients with localised disease.

Key Points

  • Pancreatic cancer will often present with a combination of obstructive jaundice, abdominal pain, or weight loss
  • Most cases are initially detected on CT scan, however require tissue diagnosis through biopsy; CA19-9 is a tumour marker used for monitoring disease progression
  • Definitive management is surgical resection, often with adjuvant chemotherapy
  • Pancreatic cancer has a 5-year survival rate of less than 5%

Endocrine Tumours of the Pancreas

Endocrine tumours of the pancreas may be functional or non-functional.

  • Functional tumours actively secrete hormones and their signs and symptoms are related to this
  • Non-functional tumours do not secrete active hormones and signs and symptoms are related purely to their malignant spread

Endocrine tumours of the pancreas are associated with multiple endocrine neoplasia 1 syndrome (MEN1), also known as Wermer’s syndrome. MEN1 typically consists of hyperparathyroidism, endocrine pancreatic tumours, and pituitary tumours (most commonly prolactinomas).

Cell Type Secreted Hormone (name of tumour) Normal Physiological Function Features of Functional Tumour
G cells Gastrin (gastrinoma) Stimulates the release of gastric acid Zollinger-Ellison syndrome, resulting in severe peptic ulcers, refractory to medical treatment, with diarrhoea and steatorrhoea
α Cells Glucagon (Glucagonoma) Increase blood glucose concentration Hyperglycaemia, diabetes mellitus, and necrolytic migratory erythema
β Cells Insulin (insulinoma) Decrease blood glucose concentration Hypoglycaemia, neuroglycopaenic symptoms
δ Cells Somatostatin (Somatostatinoma) Inhibits the release of GH, TSH and prolactin from the anterior pituitary, and of gastrin Mild diabetes mellitus, steatorrhoea, gallstones (due to inhibition of cholecystokinin), and achlorhydria (due to gastrin inhibition)
Non-islet cells Vasoactive intestinal peptide (VIPoma) Secretion of water and electrolytes into the gut. Relaxation of enteric smooth muscle. Verner-Morrison syndrome. Prolonged profuse watery diarrhoea, hypokalaemia, dehydration

Table 1 – Endocrine tumours of the pancreas.


Question 1 / 6
Which one of the following factors does not increase the risk of developing pancreatic cancer?


Question 2 / 6
In which of the following scenarios is the Courvoisier's sign most likely to be positive?


Question 3 / 6
In a Whipple's procedure, which viscera is not removed routinely as part of the operation?


Question 4 / 6
What hormone is released in excess in Zollinger-Ellison syndrome?


Question 5 / 6
Which genetic syndrome is associated with neuroendocrine functional tumours of the pancreas?


Question 6 / 6
Which imaging is the gold-standard for visualising an insulinoma?


Further Reading

Pancreatic adenocarcinoma
Bond-Smith G et al., British Medical Journal

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