Pancreatic Ca, malabsorption and alcoholism Flashcards
Pancreatic Ca - epidemiology
<2% of all malignancies but causes 6500 deaths in UK per year and incidence is rising. Commonly affects men aged >60 years. Approx 95% of patients have a mutation in the KRAS2 gene.
Pancreatic Ca - risk factors
Smoking, alcohol, carcinogens, diabetes mellitus, chronic pancreatitis and high fat diet.
Pancreatic Ca - pathology
Most are ductal adenocarcinoma which metastasise early and present late – 60% arise in the head, 25% in the body and 15% in the tail of the pancreas.
Tumours also arise in the ampulla of Vater (ampullary tumour) or pancreatic islet cells (insulinoma, gastrinoma, glucagonomas, somatostatinomas or VIPomas) and both have a better prognosis than adenocarcinoma.
Pancreatic Ca - symptoms
Tumours in the head of the pancreas present with painless obstructive jaundice whilst those in the body or tail present with epigastric pain that radiates to the back and is relieved by sitting forward. Either may cause anorexia, weight loss, diabetes or acute pancreatitis.
Pancreatic Ca - signs
Jaundice, palpable gallbladder (Courvoiser’s law – jaundice with enlarged gallbladder is unlikely to be gallstones), epigastric mass, hepatomegaly, splenomegaly, lymphadenopathy and ascites.
Pancreatic Ca - investigations
- Bloods – cholestatic jaundice, raised Ca19-9 is non-specific but may help assess the prognosis.
- Imaging – US or CT can show a pancreatic mass ± dilated biliary tree ± hepatic metastases. They can also be used to guide biopsy and provide staging prior to surgery or stent insertion.
Pancreatic Ca - management
Most ductal carcinomas present with metastases and <10% are suitable for surgery.
- Surgery – pancreatoduodenectomy (Whipple’s) if fit and tumour is <3cm with no metastases.
- Post-op chemotherapy – can be used to delay disease progression as post-op mortality is high.
- Palliation of jaundice – endoscopic or percutaneous stent insertion may help jaundice and anorexia. Rarely bypass surgery is done for duodenal obstruction or unsuccessful ERCP.
- Pain relief – disabling pain may require high doses of opiates or radiotherapy.
Pancreatic Ca - prognosis
Dismal – mean survival is <6 months and 5 year survival is <2%. Even following a Whipple’s procedure the 5 year survival is between 5-14%.
Carcinoid tumours - definition
A diverse group of tumours of enterochromaffin cell (neural crest) origin which by definition are capable of producing 5-HT.
Common sites of growth are the appendix (45%), ileum (30%) or rectum (20%). They can also occur elsewhere in the GI tract, ovary, testis and bronchi.
80% of carcinoid tumours that are >2cm in diameter across will metastasize so consider all as malignant.
Carcinoid tumours - clinical features
Initially there may be few symptoms but GI tumours can cause appendicitis, intussusception or obstruction and hepatic metastases can cause right upper quadrant pain.
Tumours may secrete bradykinin, tachykinin, substance P, VIP, gastrin, insulin, glucagon and ACTH and thyroid or parathyroid hormones.
Around 10% of carcinoid tumours are part of the MEN1 syndrome.
Carcinoid tumour - diagnosis
24 hour urinary 5-hydroxyindoleacetic acid will be raised (a 5-HT metabolite) and if liver metastases are not found look for the primary tumour e.g. chest x-ray and pelvic CT or MRI.
Carcinoid tumour - management
Give octreotide (somatostatin analogue – blocks release of tumour mediators and counters peripheral effects) but the effects lessen over time – can also be given with interferon-α.
Resection is the only cure for carcinoid tumours so it’s vital to find the primary site. At surgery the tumours have a bright yellow appearance – give octreotide cover during surgery to prevent a crisis.
Carcinoid tumour - prognosis
Median survival is 5-8 years but if metastases are present can be reduced to just 3 years.
Carcinoid Syndrome
Occurs in 5% and implies hepatic involvement – bronchoconstriction, paroxysmal flushing especially of the upper body, diarrhoea, congestive cardiac failure and carcinoid crisis.
Carcinoid Crisis
When a tumour outgrows its blood supply or is handled too much during surgery mediators flood out.
This leads to possibly life threatening vasodilation, hypotension, tachycardia, bronchoconstriction and hyperglycaemia.
It should be treated with high dose octreotide (a somatostatin analogue), supportive measures and careful management of fluid balance.
Malabsorption - symptoms and signs
- Symptoms - diarrhoea, weight loss, lethargy and steatorrhoea (stool is high in fat and difficult to flush).
- Signs of deficiency – anaemia (loss of iron, vitamin B12 and folate), bleeding disorders (loss of vitamin K), oedema (loss of protein), metabolic bone disease (loss of vitamin D) and neuropathy (loss of B12).
Malabsorption - causes
- Common in the UK – coeliac disease, chronic pancreatitis and Crohn’s disease.
- Rare – decrease in bile (in primary biliary cirrhosis, ileal resection, biliary obstruction or colestyramine), pancreatic insufficiency (malignancy or cystic fibrosis), small bowel mucosa (Whipple’s disease, tropical sprue, small bowel resection, radiation enteritis, drugs e.g. alcohol or metformin or amyloid), bacterial overgrowth (elderly or jejunal diverticula), infection or intestinal hurry (post-gastrectomy dumping or following a gastrojejunostomy).
Coeliac Disease
A T cell mediated autoimmune disease of the small bowel in which prolamin (a protein in wheat, barley, rye ± oats) intolerance causes villous atrophy and malabsorption.
It should be suspected in patient with diarrhoea with weight loss or anaemia. Disease prevalence is 1 in 300-1500 (more common in the Irish) and it can occur at any age, but peaks occur in infancy and between 50-60 years.
Coeliac - Diagnosis
You should exclude coeliac disease in any patient with IBS.
- Antibodies – α-gliadin, transglutaminase, anti-endomysial (95% specific unless IgA deficiency).
- Duodenal biopsy – taken during endoscopy shows villous atrophy, increased intra-epithelial white cells and crypt hyperplasia – these features can be reversed on a gluten free diet.
Coeliac - Management and Complications
- Management – lifelong gluten free diet – gluten free biscuits, flour, bread and pasta are prescribable.
- Complications – anaemia, secondary lactose intolerance, GI T cell lymphoma (suspect if refractory symptoms or weight loss), increased risk of malignancy, myopathies, neuropathies and osteoporosis.
Chronic Pancreatitis - Features
Epigastric pain (radiates to back and is relieved by sitting forward), bloating, steatorrhoea, weight loss or brittle diabetes. Symptoms tend to relapse and gradually worsen.
Chronic Pancreatitis - Causes
Usually alcohol and rarely familial, cystic fibrosis, haemochromatosis, pancreatic duct obstruction (by stones or a tumour), hyperparathyroidism or congenital (pancreas divisum).
Chronic Pancreatitis - Investigations
Ultrasound to detect a pseudocyst ± CT to look for calcification to confirm the diagnosis. Could also do ERCP/MRCP but risks acute attack or AXR for pancreatic calcification.
Chronic Pancreatitis - Management
- Diet – no alcohol and low fat may help.
- Drugs – analgesia, lipase e.g. Creon, fat soluble vitamins e.g. Multivite and insulin if required.
- Surgery – pancreatectomy can be used for unremitting pain, narcotic abuse or weight loss.
Chronic Pancreatitis - Complications
Pseudocyst, diabetes, biliary obstruction, local arterial aneurysm, splenic vein thrombosis, gastric varices or pancreatic carcinoma.
CAGE Questions
- Have you felt like you need to cut down on your drinking?
- Have people annoyed you by criticising your drinking?
- Have you felt guilty about drinking?
- Have you ever had an eye-opener?
Alcohol and the Liver
Normal in 50% but the rest will have raised γGT (also raised in AI hepatitis and HBV).
- Fatty liver is acute and reversible but may progress to cirrhosis if drinking continues.
- Alcoholic hepatitis is more serious and 80% develop cirrhosis and 10% hepatic failure.
Alcoholic Hepatitis - Features
Pyrexia, tachycardia, anorexia, diarrhoea and vomiting, tender hepatomegaly and ascites.
Severe alcoholic hepatitis – indicated by jaundice, encephalopathy and coagulopathy.
Alcoholic Hepatitis - Management and Complications
Patient should be admitted, screened for infection (including ascitic tap), stop alcohol consumption and manage withdrawal, give high dose B vitamins and optimise nutrition.
- Prognosis – can recover completely but severe hepatitis has a 30 day mortality rate of 50%.
Alcohol Withdrawal and Management
- Starts between 10 and 72 hours after the last drink – tachycardia, hypotension, tremor, confusion, fits, hallucinations (delirium tremens) may be visual or tactile – animals crawling on skin.
- Admit the patient, do 4 hourly observations, give 80mg Chlordiazepoxide PO (in 4 doses) for the first day and reduce the total dose by 10mg every day so it’s discontinued on day 9.
Relapse - Prevention
50% will relapse
- Acamprosate may help intense anxiety, insomnia and cravings but contraindicated in pregnancy, severe liver or renal failure and has several side effects – diarrhoea and vomiting or altered libido. It should be started once withdrawal is complete and continued for 1 year.
- Disulfiram – can be used to treat chronic alcohol dependence – it causes acetaldehyde build up with extremely unpleasant side effects to any alcohol ingestion e.g. flushing, headaches and palpitations.
