Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

Write short notes on hepatocellular carcinoma under the following headings:

– Epidemiology and pathogenesis

– Histological and immunohistochemical features

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LEARNING OUTCOMES • Describe acute liver failure and explain the common causes • Describe hepatic encephalopathy • Describe how cirrhosis presents and define decompensated/complicated cirrhosis • Summarise the causes and significance of portal hypertension, ascites & varices • Classify jaundice • Describe the causes and effects of cholestasis ACUTE LIVER FAILURE • Acute liver failure is defined as acute liver injury with encephalopathy and deranged coagulation (INR >1.5) in a patient with a previously normal liver • Acute liver failure is a rare but often life threatening syndrome that is due to hepatitis from many causes • The causes vary throughout the world. Most involve viral hepatitis but paracetamol overdose is common in UK • Histologically there is necrosis of acini involving a substantial part of the liver • Severe fatty change may be seen in pregnancy, Reye syndrome or intravenous tetracycline WHAT ARE THE CAUSES OF ACUTE HEPATIC FAILURE? SOME CAUSES OF ACUTE HEPATIC FAILURE • Virus – hepatitis A, hepatitis B, cytomegalovirus, haemorrhage fever virus • Drug – there are many, paracetamol, antibiotics, antidepressants, salicylate (Reye syndrome), NASID’s, herbal medicines • Toxins, organic solvents, mushroom toxin • Hepatic failure in pregnancy – acute fatty liver of pregnancy, HELLP syndrome SOME CAUSES OF ACUTE HEPATIC FAILURE (CONTINUED) • Vascular causes – Budd-Chiari syndrome, portal vein thrombosis • Alpha-1 antitrypsin deficiency, Reye syndrome, Wilson’s disease • Malignancies – secondary extensive metastases and infiltration • Heatstroke CLINICAL FEATURES OF ACUTE LIVER FAILURE • Jaundice • Hepatic encephalopathy • Fever, vomiting, low blood pressure, low blood glucose • Cerebral oedema in 80% of patients • Impaired gluconeogenesis Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• Kidney injury – hepatorenal syndrome • Acute tubular necrosis PORTAL HYPERTENSION • Classified by level/site of origin of portal hypertension • Commonest cause is cirrhosis • Pathogenesis in cirrhosis: Initiated: increased resistance to portal blood flow Augmented: increased portal blood flow Classification of causes of portal hypertension:

• Pre-hepatic: portal vein thrombosis • Hepatic: Cirrhosis Non-cirrhotic e.g. portal tract fibrosis due to schistosomiasis • Post-hepatic: obstruction venous outflow from liver = Budd Chiari syndrome (rare) PORTAL VENOUS SYSTEM CONSEQUENCES OF PORTAL HYPERTENSION • Porto-systemic collaterals develop: Extrahepatic – where portal venous and systemic venous circulations anastomose: – Varices (oesophageal and gastric, risk of bleed) – Rectal, periumbilical (‘caput medusae’) • Shunting of portal venous blood (reduced liver function) • Haemodynamic alterations: Ascites and hepatorenal syndrome • Splenomegaly (congestive) 20 hypersplenism (low blood counts e.g. Plts) CAPUT MEDUSAE Dilated abdominal wall veins due to collateral drainage through portosystemic anastomoses in periumbilical area OESOPHAGEAL AND GASTRIC VARICES • 30% bleed 30% die, high rate of recurrence

• Heavy alcohol users: Remember: not all upper GI bleeds are varices • Variceal bleed: Resuscitate, drugs to reduce portal blood flow Prevent/treat complications (aspiration, infection, HE) Endoscopic treatment of varices by band ligation Endoscopic sclerotherapy not favoured (complications) If above fail: placement of TIPS or surgery OESOPHAGEAL VARICES Left normal, middle mild, right severe OESOPHAGEAL AND GASTRIC VARICES Primary prevention • Screen to identify and treat moderate to severe before first bleed • Endoscopic band ligation and/or non-selective beta blockers Secondary prevention • Treat to prevent recurrent bleeding • Endoscopic band ligation and/or non-selective beta blockers ENDOSCOPIC BAND LIGATION OF VARICES Elastic band deployed at base of varix ASCITES • Fluid in peritoneal cavity • Cirrhosis commonest cause (>80%) Haemodynamic changes a/w portal hypertension Water and salt retention, preferentially accumulates as ascites in cirrhosis associated with portal hypertension

• Other causes of ascites Malignancy (ovarian cancer classic, but also GI cancers) Rare: non-cirrhotic portal hypertension Rare: heart failure, pancreatitis, TB • Abdominal distension, shifting/flank dullness ASCITES (CONTINUED) • Paracentesis = tap of ascites fluid Diagnostic tap – do cell count, microbiology (blood culture bottles), albumin, cytology Therapeutic tap – diuretic-resistant ascites in cirrhosis • Treatment Na+ restriction, diuretics (spironolactone) Therapeutic paracentesis Avoid NSAID’s High index of suspicion for infection (low threshold for paracentesis) Diuretic-resistant = refractory ascites SPONTANEOUS BACTERIAL PERITONITIS (SBP) • Infection of ascites fluid without evidence of surgicallytreatable intra-abdominal cause • Infection associated with cirrhosis (E. coli, Klebsiella) • Early diagnosis, prompt treatment, better outcome • Subtle/silent presentation • Low threshold for paracentesis of ascites fluid

• Suspect: Fever, abdominal pain/tenderness, altered mental state Treat if ascites fluid cell count >250 polys/mm3 Antibiotic prophylaxis if high risk (e.g. previous SBP or bleed) HEPATORENAL SYNDROME • Renal impairment secondary to liver disease • Haemodynamic effects of portal hypertension reduce renal perfusion, typically a/w ascites • Diagnosis of exclusion – no other kidney pathology: Hypovolaemia/shock (e.g. infection, bleeding) Acute tubular necrosis (shock or nephrotoxic drugs) • Poor prognosis HEPATIC ENCEPHALOPATHY Spectrum of neuro-psychiatric abnormalities seen in a/w liver dysfunction and/or porto-systemic shunting • Functional disturbance of brain, potentially reversible • If severe a/w cerebral oedema and cerebral hypoperfusion Classification: • Type A: acute liver failure • Type B: porto-systemic shunting with normal liver • Type C: cirrhosis (= decompensation) • Episodic (may be recurrent) HE +/- persistent HE • Episodic HE may be precipitated or not • Spectrum of effects: on consciousness, behaviour, intellectual function, neuromuscular function STAGES OF HEPATIC ENCEPHALOPATHY Stages of Hepatic Encephalopathy Confusion Drowsiness Somnolence Coma 1 2 Stage 3 4 STAGES OF HEPATIC ENCEPHALOPATHY Minimal HE may be revealed by psychometric testing Affects social function/work life/behaviour, fitness to drive Minimal HE + stage 1 HE = covert HE, stages 2 to 4 = overt HE PSYCHOMETRIC TESTING FOR COVERT HE Reitan number connection test part A Reitan number connection test part B PSYCHOMETRIC TESTING FOR COVERT HE Psychometric Hepatic Encephalopathy Score (PHES) HEPATIC ENCEPHALOPATHY 2 • Why does it happen? Reduced detoxification (endogenous and exogenous, including from gut) due to reduced liver function Unprocessed portal blood shunted through/past liver • Pathogenesis – no definite single cause Ammonia accumulation (nitrogenous compounds) Altered neurotransmission (GABA, glutamate), glial fxn • Precipitants in known cirrhosis: Infection Bleeding, other causes of hypoperfusion Dehydration (diuretics, paracentesis, V & D) Drugs (sedatives – opiates, benzos) or alcohol Constipation Need for TIPS or surgical shunt TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT HEPATIC ENCEPHALOPATHY 3 Treatment: • Identify and correct precipitating factors Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• Reduce ammonia production in enema, empty bowel of nitrogenous substances Lactulose Non-absorbable antibiotic (rifaximin) Fluids Stop diuretic therapy INVESTIGATION OF LIVER & BILIARY TRACT DISEASE • Presentation: Screen or vague/non-specific symptoms (“fishing” with tests) Known possible risk factors Clinically obvious presentation • History (risk factors) & examination • Liver blood tests (as screen or to establish cause) • Liver imaging (radiology and gastroenterology) • Liver biopsy • Non-invasive assessment of hepatic fibrosis LIVER BLOOD TESTS • “Liver profile” = ALT, AST, Alk Phos, GGT, bilirubin, albumin • Related to liver cell (hepatocellular) damage: Transaminases (ALT, AST) • Related to obstruction to bile flow (cholestasis):

Alkaline phosphatase, GGT Bilirubin • Related to liver function Bilirubin – abnormality not liver or biliary tract specific Albumin – may reflect chronic damage Coagulation function (PT/INR) – acute damage HEPATOCELLULAR DAMAGE LIVER ENZYMES • Alanine transaminase (obsolete ‘SGPT’) • Aspartate transaminase (obsolete ‘SGOT’) Both leak from damaged hepatocytes ALT sensitive/specific marker for hepatocellular damage AST less specific, also in muscle, myocardium, kidney Level of rise poor correlation with severity/prognosis Very high in acute hepatocellular damage May be only mildly elevated or normal despite chronic liver disease AST/ALT ratio can be informative – Usually 2 suggests alcohol-related damage OBSTRUCTIVE (CHOLESTATIC) LIVER ENZYMES Alkaline phosphatase • Situated on hepatocyte border of bile canaliculi

• Hepatocytes react to obstruction to bile flow with Alk Phos leak • Other sources: bone, placenta Gamma-glutamyl transferase (GGT) • Obstruction to bile flow, therefore: • Good for correlating with elevated alkaline phosphatase to demonstrate that Alk Phos is of liver origin • Also induced by alcohol, drugs • Very sensitive but not specific at all • Isolated rise not usually investigated LIVER FUNCTION TESTS Albumin • Long half life • Low albumin therefore reflects chronic injury to liver • Very non-specific but useful in context Clotting time (prothrombin time/INR) • Clotting factors short half life • Rise correlates with degree of acute damage to liver

• PT sent in coagulation tube to haematology lab Bilirubin ADDITIONAL LIVER BLOOD TESTS FOR CAUSE • Viral serology A, B, C – sometimes EBV, CMV, E • Iron storage status Transferrin saturation / % sat. of total iron binding capacity Ferritin ADDITIONAL LIVER BLOOD TESTS FOR CAUSE (CONTINUED) • Immunological injury/reaction (autoimmune) Auto-antibodies (ANA, SMA, anti-LKM, AMA, ANCA) Immunoglobulin G and M levels • Copper metabolism (Wilson’s disease, very rare) Caeruloplasmin • Alpha-1-antitrypsin levels (A1AT def., very rare) BILIRUBIN, JAUNDICE & CHOLESTASIS • Bilirubin normal 50umol/l • “Biochemical jaundice” >182x/ULN? INTERPRETATION OF LIVER BLOOD TESTS (CONTINUED) Persisting or transient? • Some recommend re-test single mildly abnormal liver blood result after interval of a few months How far do you go? • Investigate all or some of these patients? • Concern: miss treatable disease, few %

• History (alcohol, meds, obesity/DM, viral) & examination • Initial work up if liver disease possible/likely • Blood tests: viral serology, iron storage status, autoimmune • Ultrasound HEPATOCELLULAR DAMAGE PATTERN OF ABNORMAL LIVER BLOOD TESTS • Very high (>1000) Acute viral infection, drugs, ischaemia Acute liver failure – PT best guide to severity/prognosis Sometimes, acute flares of chronic disease • Less marked Alcohol, NAFLD, drugs, chronic viral disease, autoimmune hepatitis, HFE, passive congestion Cirrhosis – Suspect if low albumin or low platelets – AST/ALT >2 implies alcohol (?GGT, ?MCV) OBSTRUCTIVE/CHOLESTATIC PATTERN OF ABNORMAL LIVER BLOOD TESTS • Infiltrative disease Diffuse processes: sarcoid, amyloid, lymphoma • Metastatic disease in liver May cause local obstruction or diffuse infiltration • Intrahepatic cholestasis Chronic autoimmune disease (PBC, PSC)

Drugs, pregnancy, sepsis, rare inherited • Extrahepatic obstruction/cholestasis Stone Structure Tumour LIVER IMAGING • Ultrasound Dilated ducts, gallstones, focal liver lesions Liver texture (echogenicity) and border (inhomogeneity) Not sensitive for cirrhosis or mild degrees of fatty change • MRCP (magnetic resonance choledochopancreatography) • CT and/or MR (each +/- contrast enhancement) • Endoscopic ultrasound (EUS) LIVER IMAGING (CONTINUED) • ERCP (endoscopic retrograde choledochopancreatography) Diagnostic with therapeutic intent in addition (treatment of CBD stone, drain biliary tract, stent obstruction)

• PTC (percutaneous transhepatic cholangiography) Decompression/visualisation of obstructed biliary system ANATOMY OF ERCP ERCP IMAGE Biliary tract outlined in retrograde fashion by contrast introduced at ampulla via endoscope LIVER BIOPSY • Indications: • Diffuse liver disease Diagnosis of cause Grade necroinflammatory activity and stage (fibrosis) Sampling variability is an issue for diffuse disease • Focal liver lesion Cyst vs haemangioma vs tumour-like lesion vs tumour (benign, malignant, primary or secondary) US, CT, MR + context usually diagnostic of most lesions LIVER BIOPSY (CONTINUED) Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• Approaches: Percutaneous – radiological guidance, needle core of tissue Transjugular – if coagulopathy Laparoscopic – focal lesion • Risks: pain, bleed, bile leak, trauma 2-3% hospitalised, 1/10000 mortality C/I: clotting problems, anti-clotting drugs, biliary obstruction Do: platelet count/coag screen, group and screen blood • Balance risks of biopsy versus benefit Will it affect management (prognosis, therapy)? Biopsy performed with diminishing frequency • Standard handling in laboratory: H&E plus routine “special” stains for fibrosis and iron Immunohistochemistry for tumours NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS • Serum markers APRI (AST to prothrombin ratio index), NALFD fibrosis score Proprietary (e.g. Fibro Test, Enhanced Fibrosis Score [EFS]) • Transient elastography FibroScan Liver stiffness: ultrasound assessment of velocity of elastic shear wave signal Best at identifying ends of spectrum • Replace biopsy? LEARNING OUTCOMES • Classify liver tumours and demonstrate an understanding of their relative frequency • Describe Hepatocellular carcinoma • Define cholangiocarcinoma • Describe how pancreatic cancer presents • Discuss the frequency and significance (or otherwise) of finding gallstones

• Define acute cholecystitis • List the causes and effects of extra hepatic bile duct obstruction • Discuss the common causes and presentation of acute pancreatitis and chronic pancreatitis AN APPROACH TO LIVER TUMOURS • Non-neoplastic versus neoplastic Non-neoplastic lesions can mimic neoplasms Cysts, haemangiomas, regenerative tumour-like lesions, abscesses: US, CT, MR + context diagnostic • Benign versus malignant neoplasms • Primary versus secondary malignancies • Consider different types of primary neoplasm Depending on tissue type of origin, e.g. for malignancies: carcinoma, possibly of different types, sarcomas of different types, lymphoma etc.

• But focus/highlight commoner entities PRIMARY LIVER TUMOURS Benign • Hepatic adenoma (= liver cell adenoma, anabolic steroids, (OCP)) • Bile duct adenoma (rare) • Haemangioma Malignant • Hepatocellular carcinoma (=liver cell carcinoma, hepatoma, HCC) • Intrahepatic cholangiocarcinoma (=intrahepatic bile duct adenocarcinoma) • Haemangiosarcoma (textbook rarity) SECONDARY TUMOURS/LIVER METASTASES • Commonest ‘liver tumour’ in Europe/N America • Carcinoma – primary in GI tract, lung, breast • Other malignancies can infiltrate liver e.g. lymphoma, leukaemia • Metastases may obstruct bile flow Early: few symptoms/effects, Alk Phos raised Late: rising bilirubin, jaundice • Generally poor prognosis

• Identify primary site of origin – treatment • Surgery for isolated colorectal metastases IMMUNOHISTOCHEMISTRY IS USED IN LIVER METASTASIS HISTOLOGY • CK20, CDX2 • TTF1 • S100, Melan A, HMB, SOX10 – Large intestine Lung Melanoma WHAT IS IN THIS IMAGE? A. Cirrhosis B. Metastases to liver GROSS APPEARANCE OF METASTASES (SECONDARIES) TO LIVER Multiple pale deposits are metastases (don’t confuse with cirrhosis, not diffuse change) HEPATOCELLULAR CARCINOMA • Europe/North America relatively uncommon • East and SE Asia/Africa common • Associated with cirrhosis/chronic hepatitis (>90%) • Can occur in non-cirrhotic fibrotic HBV livers • Single mass or multifocal, may have vascular invasion

• Metastases not as usual as in some other tumour types • Presentation High incidence areas – co-presents with or precedes cirrhosis, in relatively young patients Low incidence areas – decompensation of cirrhosis, 3% HCC/yr, vague/changing symptoms HEPATOCELLULAR CARCINOMA Diagnosis • Radiology: US, specific contrast-enhanced CT and/or MRI protocols • Assessment of nodules in cirrhosis, >1cm or enlarging • Alpha-fetoprotein (AFP): ‘tumour marker’ • Biopsy rarely necessary Screening • High risk patients (compensated cirrhosis), every 6/12 •

US • AFP blood test – alone not specific/sensitive enough Prevention • Treatment of cause of underlying chronic liver disease? • Prevention of chronic liver disease (HBV vaccination) HEPATOCELLULAR CARCINOMA Treatment • Resection if early • OLT • Local ablative treatments: radiofrequency, arterial chemoembolization Prognosis – depends on: • Stage • Degree of liver function impairment • Co-morbidity • Typically poor but in selected cases 5 year survival of 50% Aetiology • Cirrhosis (HBV/HCV/HFE > other causes cirrhosis?) • Chronic HBV directly oncogenic? • Aflatoxins – fungal contaminants of food stores GROSS APPEARANCE OF HEPATOCELLULAR CARCINOMA MICROSCOPIC APPEARANCE OF HCC Tumour cells resemble hepatocytes but show pleomorphism CHOLANGIOCARCINOMA

• Adenocarcinoma arising from bile duct epithelium Intrahepatic or extrahepatic location • Commonest site at hilum of liver Klatskin tumour = obstructing bifurcation of CHD • Intrahepatic cholangiocarcinoma a minority of primary liver malignancy (10%) • Associations: PSC Rare: chronic fluke infestation, congenital biliary abnormalities Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• Diagnosis difficult and often late, outcome poor • Selected cases – surgical resection • Typically, palliate obstruction with stent placement CHOLANGIOCARCINOMA IMAGE PANCREAS • • • • • Retroperitoneal location 2 components, embryologically distinct Exocrine 98%: makes digestive enzymes Endocrine: islets of Langerhans, hormones Exocrine composed of glandular acini grouped into lobules • Exocrine secretions drain via ducts, joining to form pancreatic duct HISTOLOGY OF NORMAL PANCREAS Small pancreatic duct (centre) surrounded by exocrine pancreatic glandular acini. Pale collection of cells (left centre) is islet of Langerhans PANCREATIC TUMOURS Exocrine pancreas • Malignant: pancreatic (ductal) adenocarcinoma • Other less common tumours, sometimes cystic • May be benign or have intermediate behaviour

• Some recognised as precursors to pancreatic ca Endocrine • Pancreatic neuroendocrine tumours rare • Behaviour difficult to predict • Classified by hormone type produced • Hormone may cause clinical symptoms • Association with parathyroid hyperplasia and pituitary adenomas in inherited MEN type 1 syndrome PANCREATIC CARCINOMA • • • • • Adenocarcinoma, arising from pancreatic ducts Common: 5th/6th by rank of cancer deaths M>F, 80% >60 years 60-70% from head, rest from body & tail Spread Direct local: peritoneum (vessels, nerves), duodenum, CBD = ‘locally advanced’ Lymph nodes or to liver (50% metastatic at diagnosis) • Risk factors (relatively weak) Smoking, DM, chronic pancreatitis Family history (5%) PANCREATIC CARCINOMA Symptoms

• Typically symptomatic only with advanced disease • Easily missed • Anorexia, weight loss • Painless obstructive jaundice (tumours in head) • Vague abdominal pain, may radiate to back • Rare: palpable mass, thrombotic tendency Migratory thrombophlebitis = Trousseau’s sign Diagnosis • CA 19-9 serum marker for pancreatico-biliary cancer Not useful in diagnosis, used for response/relapse assessment • Imaging (US, CT, EUS), FNA cytology via EUS • Avoid unnecessary invasive investigation in majority PANCREATIC CARCINOMA Prognosis

• 5 year survival M, older age group • Presents late, vague symptoms, outlook poor • Clinical problem: gall bladder “polyps” often identified at US Question is: could they be neoplasms of the gall bladder (adenomas or carcinomas)? If small/non-progressive, likely to be harmless nonneoplastic cholesterol “polyps” CAUSES OF EXTRAHEPATIC BILE DUCT OBSTRUCTION • Gallstones in common bile duct • Tumour Adenocarcinoma of pancreas

Extra-hepatic bile duct adenocarcinoma • Benign stricture (post-operative or PSC) • Mass outside CBD/CHD compressing duct Mirizzi syndrome (external compression from stone in neck/cystic duct of GB) Primary tumour or metastases in lymph nodes EXTRAHEPATIC BILE DUCT OBSTRUCTION • Courvoisier’s law – historic interest only • Investigation US shows dilated ducts above obstruction Cause may need investigation by MRCP or EUS May perform ERCP for diagnosis if treatment also considered

• Treatment is decompression +/- treat cause Stones ERCP with sphincterotomy +/- stone removal CBD exploration at surgery (laparoscopic or open) • Structure: stent • Tumour: stent Stenting usually via ERCP ASCENDING (ACUTE) CHOLANGITIS • Infection in static, obstructed bile • High fever, pain, jaundice = Charcot’s triad • Add hypotension, altered mental state = Reynolds’ pentad • Requires urgent decompression HEPATIC ABSCESS • Biliary tract disease a/w ascending infection commonest cause • Seeding from systemic sepsis may sometimes be the cause • Historically, common cause was spread via portal vein from intra-abdominal sepsis • Drain and antibiotics Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• (Amoebic abscess) ACUTE PANCREATITIS • • • • Acute inflammation of pancreas 10-20/million, mortality ?5% (higher if severe) Single or recurrent attacks Pathogenesis Premature (intra-pancreatic) activation of pancreatic enzymes Once initiated, irreversible cascade (auto-digestion) May trigger systemic inflammatory response syndrome (SIRS) if severe • Obstructing stone at lower end CBD causes reflux of bile/concentration of pancreatic juices Hepatocellular Carcinoma Epidemiology and Pathogenesis Essay.

• Alcohol direct toxic effect MECHANISM OF PANCREATITIS SEVERITY OF ACUTE PANCREATITIS Mild acute pancreatitis (80% cases) • Self limiting disease • Interstitial oedematous acute pancreatitis on imaging, non-necrotizing Severe acute pancreatitis (20% cases)

• Necrotizing inflammation of pancreas and surrounding tissue (peri-pancreatic fat) EFFECTS OF SEVERE ACUTE PANCREATITIS • Systemic inflammatory response syndrome Hypovolaemia, hypotension, ARDS, acute renal failure, disseminated intravascular coagulation (DIC) • Hypocalcaemia, hyperglycaemia, ileus • Local complications Extensive necrosis (acute necrotic collection), risk secondary infection Later: pseudocyst, fistula • Mortality a/w acute pancreatitis two phases First week (50%) a/w SIRS and complications Second week (50%) a/w necrosis and sepsis CAUSES OF ACUTE PANCREATITIS • Gallstones (F>M) • Alcohol (M>F) • Post-ERCP (5%) • Idiopathic (10%) – biliary microlithiasis • Miscellaneous uncommon causes (5%) Trauma, ischaemia, major surgery Drugs, viral Hypercalcaemia, hyperlipidaemia Hereditary pancreatitis DIAGNOSIS OF ACUTE PANCREATITIS Symptoms • Epigastric pain, may radiate into back

• ‘Acute abdomen’, seen by surgeons • If severe: differential diagnosis – MI, ruptured AAA, perforated or ischaemic abdominal organ Blood tests • Blood amylase higher than 3X normal • Amylase short half life • Lipase used in future? • If equivocal, ?radiology • Try and identify cause, avoid immediate laparotomy CHRONIC PANCREATITIS • Patchy, irreversible fibrosis, ongoing inflammation • Pancreatic function impaired (exocrine>endocrine) • Distortion of ductal system Strictures, dilatation and cysts behind strictures, pancreatic ductal stones Causes: • Alcohol • Idiopathic • Childhood causes including cystic fibrosis • CF more typically a/w pancreatic insufficiency due to damage but without clinical ‘chronic pancreatitis’ CHRONIC PANCREATITIS Symptoms:

• Pain (dull, epigastric, radiating to back) • Weight loss • Steatorrhoea and malabsorption • Secondary diabetes mellitus Treatment: • Analgesia (opiates), enzyme supplements Diagnosis: • Difficult, sometimes diagnosis of exclusion • Amylase not useful • Tests of pancreatic function not routine • Imaging in advanced disease PANCREATIC PSEUDOCYST • Collection of pancreatic fluid in disrupted tissue in or adjacent to pancreas • Defined wall but not a true cyst (no epithelial lining) • Causes: acute or chronic pancreatitis, pancreatic surgery or trauma • Complications: pain/pressure, infection, erosion with fistula or blood vessel damage •