Pancreatic Ca, malabsorption and alcoholism

Question 1

Pancreatic Ca - epidemiology

Answer 1

<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.

Question 2

Pancreatic Ca - risk factors

Answer 2

Smoking, alcohol, carcinogens, diabetes mellitus, chronic pancreatitis and high fat diet.

Question 3

Pancreatic Ca - pathology

Answer 3

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.

Question 4

Pancreatic Ca - symptoms

Answer 4

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.

Question 5

Pancreatic Ca - signs

Answer 5

Jaundice, palpable gallbladder (Courvoiser’s law – jaundice with enlarged gallbladder is unlikely to be gallstones), epigastric mass, hepatomegaly, splenomegaly, lymphadenopathy and ascites.

Question 6

Pancreatic Ca - investigations

Answer 6

• 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.

Question 7

Pancreatic Ca - management

Answer 7

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.

Question 8

Pancreatic Ca - prognosis

Answer 8

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%.

Question 9

Carcinoid tumours - definition

Answer 9

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.

Question 10

Carcinoid tumours - clinical features

Answer 10

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.

Question 11

Carcinoid tumour - diagnosis

Answer 11

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.

Question 12

Carcinoid tumour - management

Answer 12

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.

Question 13

Carcinoid tumour - prognosis

Answer 13

Median survival is 5-8 years but if metastases are present can be reduced to just 3 years.

Question 14

Carcinoid Syndrome

Answer 14

Occurs in 5% and implies hepatic involvement – bronchoconstriction, paroxysmal flushing especially of the upper body, diarrhoea, congestive cardiac failure and carcinoid crisis.

Question 15

Carcinoid Crisis

Answer 15

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.

Question 16

Malabsorption - symptoms and signs

Answer 16

• 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).

Question 17

Malabsorption - causes

Answer 17

• 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).

Question 18

Coeliac Disease

Answer 18

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.

Question 19

Coeliac - Diagnosis

Answer 19

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.

Question 20

Coeliac - Management and Complications

Answer 20

• 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.

Question 21

Chronic Pancreatitis - Features

Answer 21

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.

Question 22

Chronic Pancreatitis - Causes

Answer 22

Usually alcohol and rarely familial, cystic fibrosis, haemochromatosis, pancreatic duct obstruction (by stones or a tumour), hyperparathyroidism or congenital (pancreas divisum).

Question 23

Chronic Pancreatitis - Investigations

Answer 23

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.

Question 24

Chronic Pancreatitis - Management

Answer 24

• 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.

Question 25

Chronic Pancreatitis - Complications

Answer 25

Pseudocyst, diabetes, biliary obstruction, local arterial aneurysm, splenic vein thrombosis, gastric varices or pancreatic carcinoma.

Question 26

CAGE Questions

Answer 26

• 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?

Question 27

Alcohol and the Liver

Answer 27

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.

Question 28

Alcoholic Hepatitis - Features

Answer 28

Pyrexia, tachycardia, anorexia, diarrhoea and vomiting, tender hepatomegaly and ascites.

Severe alcoholic hepatitis – indicated by jaundice, encephalopathy and coagulopathy.

Question 29

Alcoholic Hepatitis - Management and Complications

Answer 29

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%.

Question 30

Alcohol Withdrawal and Management

Answer 30

• 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.

Question 31

Relapse - Prevention

Answer 31

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.