Contents
Introduction
Pancreatic cancers are 95% exocrine, adenocarcinomas. These affect the duct or surround the duct. The remaining 5% are neuroendocrine tumours e.g. insulinomas, glucagonomas (the former being the more common). This article pertains to adenocarincoma, with the latter briefly mentioned at the end.
Typically, the more common adenocarcinoma occludes the pancreatic duct or branches of it. 70% occur at the head, causing (an initial) painless jaundice as the obstructed bile cannot flow through the sphincter of Oddi and refluxes back up through the biliary tree and into the blood. Tail tumours are more likely to be neuroendocrine than head tumours.
These tumours nearly always present late and nearly always have a terrible prognosis, with mean survival from diagnosis of 6-10 months depending on the presence or absence of metastases respectively. >80% have metastasised at diagnosis.
Epidemiology
- Increasing in incidence rising 4% per decade
- Nearly 9000 new diagnoses yearly in the UK
- 10th most common cancer
- 5% of all cancer deaths but only 3% of all cancer diagnoses
- In excess of 8,000 annual deaths (2011 data, Cancer research UK)
- 5 year survival <2%
>90% have KRAS mutations, and many other mutations besides.
Risk factors
- Age (above 60s, very rare below 40)
- Smoking (RR 1.7)
- Diabetes mellitus
- Helicobacter pylori infection status (may be subclinical, often is)
- Partial gastrectomy
- Family history and genetics (<5% of cases)
- Obesity
- Male sex (RR 1.3)
Dubious but commonly asked by patients: red meat consumption, sugar intake, poor vegetation intake.
Note: whilst chronic pancreatitis is associated, alcohol and gallstones (a known proponent of chronic pancreatitis) per se are not associated with pancreatic cancer: contrary to the Oxford handbook of clinical medicine. Chronic pancreatitis is thought to be required for the dysplastic transformation (personal communication on wards).
Symptoms
- Pain is found in 70% of presentations (similar to that seen in pancreatitis – epigastric radiating to the back. Remember the pancreas is retroperitoneal apart from the tail, found in the splenorenal ligament)
- Anorexia and nausea
- Diarrhoea
- Cachexia
- Jaundice (obstructive picture with pale stools and dark urine)
- Itch (due to peripheral bilirubin)
Symptoms of advanced disease
- Pulmonary emboli – SOB, chest pain
- Diabetes mellitus – polyuria, polydipsia
- Ascites – abdominal fullness
Courvoisier’s law: in the presence of painless jaundice, a palpable gallbladder is unlikely to be due to gallstones. I.e potentially pancreatic cancer; it’s spread to the gallbladder already. Whilst pain is the most common presentation, painless jaundice is always sinister.
Thrombophelbitis/Trousseau’s sign: uncommon but can occur e.g. portal venous thrombosis.
On examination
- Typically: cachectic, jaundiced old patient presenting with abdominal pain/breathlessness/diarrhoea.
- Masses may be felt in the epigastric region – either hepatomegaly or gallbladder
- Ascites
Blood tests
- Obstructive jaundice picture (raised bilirubin and alkaline phosphatase, may have hepatocellular dysfunction too with raised ALT and AST)
- Hyperglycaemia
- Anaemia
- Hypokalaemia (if vomiting or diarrhoea)
- Hypercalcaemia (may be related to chronic pancreatitis or Trousseau’s sign of latent malignancy)
- CA19-9 is a tumour marker is 77% sensitive and 87% specific if significantly raised and is more likely to be raised if the cancer has metastasised.
Investigations
Typically
- US – sensitive to masses in the biliary tree and pancreatic ducts
- CXR – Can determine lung involvement
- Endoscopic US or biopsy
- If there is a suspicious mass on US, endoscopy can help confirm the diagnosis. Histology is not normally required for formal diagnosis.
- CT/PET staging
Treatment
The mainstay of treatment is palliative with significant analgesia required. Many patients ask for or are recommended palliative endoscopic stenting to help control their symptoms. Bilirubin itch is debilitating, but endoscopic stenting can provide a good remedy. Patients will often be on PCA (patient-controlled analgesia) and may attend hospital for symptomatic ascites drainage. <20% have an operative option available.
Surgery
- Whipple’s procedure (head) – a massive operation and rarely done, but potentially curative. A Pancreatoduodenectomy.
- Distal pancreatectomy (tail)
Chemotherapy
- Gemtacitabine (weekly IV infusion) prolongs median survival and improves QoL in some, but many do not wish for chemotherapy.
Radiotherapy
- Mostly reserved for adjuvant usage in potentially ‘curable’ tumours
Prevention
Low dose aspirin for 5 years has been shown to reduce the risk of pancreatic cancer by around 75%.
(Effect of aspirin on long-term risk of death due to pancreatic cancer: analysis of individual patient data from randomised trials. Rothwell et al 2011, Lancet)
Neuroendocrine tumours
Glucagonomas and insulinomas are much rarer.
They can be watchfully waited upon, have RF ablation, surgically excised and so on. These can be associated with MEN-1, particularly insulinomas