Pancreatic carcinoma Flashcards
Are majority of pancreatic cancers exocrine or endocrine in origin?
Exocrine (90%)
At what age is diagnosis of pancreatic cancer made?
Does it affect men or women more?
Diagnosis made in 70’s ; late presenting
Men>women
What type of pancreatic cancer is most common?
Adenocarcinoma (96%) of ductal origin
What are the risk factors of pancreatic cancer?
Smoking Excess alcohol Excess coffee Excess aspirin Hx of diabetes & chronic pancreatitis Family Hx of pancreatic cancer
*Risk of pancreatic cancer highest in patients with a (PRSS1) mutation predisposing to chronic pancreatitis.
Which tissue does pancreatic cancer arise from?
How does it evolve from pre-malignant to cancerous tissue?
The cancer originates from the ductal epithelium.
Progression:
Minimally dysplastic epithelium => Severe dysplasia => invasive carcinoma
What is the term given to the precursor of pancreatic cancer?
Pancreatic intraepithelial neoplasia
What’s the most common mutation in pancreatic cancer?
> 90% cases KRAS mutations
Anatomically, where do you commonly find tumours on a pancreas?
Head of the pancreas
2/3 of pancreatic cancer here
What are the clinical features of pancreatic cancer?
Abdominal pain ; radiates to back ; partially relieved by sitting forward
Anorexia & weight loss
New onset of depressive symptoms (early symptom)
(Painless) Jaundice (compression of distal common bile duct)
Pale stool, dark urine & itching with bile duct obstruction prior to/in absence of jaundice
Malabsorption and steatorrhoea
Diabetes (50%)
Less common:
Skin nodules
Polyarthritis
Thromboembolic phenomena
What are the signs of pancreatic cancer?
Weight loss Jaundice Scratch marks - pruritus Palpable gall bladder (Courvoisier's sign) Abdominal mass - advanced local disease Liver mets - hepatomegaly
How do you diagnose pancreatic cancer?
- Trans-abdominal ultrasound (initial imaging investigation):
Confirms dilated intra-hepatic bile duct in the presence of bile duct obstruction
Confirms pancreatic head tumour
Not good for pancreas body & tail tumours because of overlying bowel gas
- Contrast-enhanced CT scan:
Confirms the presence of most pancreatic adenocarcinoma
Confirms lymph node involvement & metastatic disease (used for diagnosis + staging) - Endoscope ultrasound:
Small tumours which may be missed on CT
Confirms cytology
(Most sensitive non-surgical procedure) - Tumour markers
Patients with pancreatic cancer present at late stage
Upper gut symptoms in these patients first prompt for upper GI endoscopy
What are the differential diagnosis for pancreatic cancer?
In presence of painless jaundice or pain radiating to back => always think pancreatic cancer first
Auto-immune pancreatitis ;
Abdominal aortic aneurysm ;
Ampullary carcinoma
How do you treat curative pancreatic cancer?
Curative treatment: Whipple procedure (aka pancreaticoduodenectomy, is a complex operation to remove the head of the pancreas, the first part of the small intestine (duodenum), the gallbladder and the bile duct).
Tumours of body and tail resected via laparoscopic surgery.
Chemotherapy neo/adjuvant (Gemcitabine, fluorouracil) may improve survival
How do you manage non-curative pancreatic cancer?
Palliative care - managing complications of pancreatic cancer
Pain: opiates
Nutritional deficit: Dietician support, pancreatic enzyme supplement (due to malabsorption), management of diabetes
Obstructive jaundice: assoc with anorexia, nausea and pruritus => endoscopic stenting improves this
Duodenal obstruction: endoscopic stenting (assoc. with tumours in head or uncinate process of pancreas)
Chemotherapy: may exacerbate nutritional deficit
What is the prognosis of pancreatic cancer?
Very poor. Mean survival <6 months. 5yr survival 3% ; 5-14% with whipple’s
What are pancreatic neuroendocrine tumours and which cells do they arise from?
Pancreatic neuroendocrine tumours are a group of cancers arising from islets of langerhans cells, secreting a variety of hormones including insulin, glucagon and also ectopic hormones i.e. gastrin, adrenocorticotrophin, growth hormone
Pancreatic neuroendocrine tumours secrete most commonly secret which hormone?
Insulin
What is the clinical presentation of pancreatic neuroendocrine tumour?
Majority symptoms dependent on the hormone released from the tumour (25-50% of tumours)
The rest are either non-functioning tumours = incidental finding or symptoms related to tumour mass i.e. obstruction, jaundice, bleeding, abdominal mass
10-15% pancreatic neuroendocrine tumours are linked to inherited syndromes. What are these syndromes?
- Multiple endocrine neoplasia type 1 (MEN-1) => hereditary conditions assoc. with tumours of endocrine (hormone producing) glands i.e. islet cells of pancreas, parathyroid glands, pituitary gland
- Hippel-Lindau syndrome (VHL) => hereditary conditions assoc. with tumours arising in multiple organs
There are 5 clinical syndrome described within pancreatic neuroendocrine tumours. Describe gastrinoma.
How does a gastrinoma result in duodenal ulcer disease?
Accounts for 1 in 1000 cases of duodenal ulcer disease.
Ulceration results from hyper secretion of gastric acid 2nd to high serum gastrin concentration secreted by pancreatic endocrine tumour.
Diagnosis is confirmed by high gastrin levels. High dose PPI given for symptomatic relief.
There are 5 clinical syndrome described within pancreatic neuroendocrine tumours. Describe VIPoma.
How does VIPoma cause secretory diarrhoea?
What is the clinical presentation?
VIPoma is an endocrine pancreatic tumour producing vasoactive intestinal polypeptide.
This causes secretory diarrhoea 2nd to stimulation of adenyl cyclase in enterocytes.
Clinical presentation: Watery diarrhoea, hypokalaemia, metabolic acidosis
There are 5 clinical syndrome described within pancreatic neuroendocrine tumours. Describe Glucagonoma.
Glucagonomas = rare a-cell tumour which can cause migratory necrolytic dermatitis, weight loss, diabetes, deep vein thrombosis, anaemia, hypoalbuminaemia.
Diagnosis = pancreatic glucagon serum levels
There are 5 clinical syndrome described within pancreatic neuroendocrine tumours. Describe Stomatostatinoma.
Rare malignant D-cell tumours of the pancreas. This can cause diabetes, gallstones and diarrhoea/steatorrhea.
Diagnosed by high somatostatin level.
There are 5 clinical syndrome described within pancreatic neuroendocrine tumours. Describe insulinoma.
What are its presenting features?
Insulinomas are pancreatic islet cell tumours that secrete insulin. Most are sporadic but some arise from neural crest tissue.
Presenting features: Diplopia Sweating, palpitations, weakness Confusion or abnormal behaviour Loss of consciousness Grand mal seizures
Whipple’s triad is the basis of clinical triad. What is the triad?
How is the diagnosis confirmed?
- Symptoms are associated with fasting or exercise
- Hypoglycaemia is confirmed during these episodes
- Glucose relieves the symptoms
Diagnosis is confirmed by presence of hypoglycaemia in assoc. with inappropriately high insulin levels hypoglycaemia
What investigations are carried out to diagnose suspected pancreatic neuroendocrine tumours?
Biochemical diagnosis:
Measurement of circulatory chromogranin A
Measurement of specific hormones i.e. gastrin, insulin, glucagon, VIP
Histopathology diagnosis:
Positive staining from chromogranin A and specific hormones
Which imaging techniques can be used for tumour localisation?
Cross-sectional imaging inc. CT and MRI
- Majority neuroendocrine tumours express somatostatin receptors => radio labelled somatostatin analogue helps with tumour localisation using scintigraphy
- PET w/ CT used for localisation of primary tumour & metastases
- Endoscopic ultrasound (EUS) is the most sensitive => detecting small primary pancreatic neuroendocrine tumours.
This also allows fine needle aspirate sampling of lesion to allow cytology diagnosis.
What is the only possible cure of pancreatic neuroendocrine tumours?
Surgical resection of primary lesions = optimal management/only possible cure
How else can neuroendocrine tumours be managed?
- Somatostatin analogues: control hormone related symptoms and has a tumour modulating effect.
- Chemotherapeutic agents
Cystic lesions of pancreas as common. 75% are pseudocysts and 15% are true pancreatic cystic neoplasms. Pancreatic cystic neoplasms have a high tendency to become malignant.
What are the 4 different types of pancreatic cystic neoplasms?
- Serous cyst adenomas
- Solid pseudopapillary neoplasms
- Mucinous cyst adenomas
- Intraductal papillary mutinous neoplasms
