Hepatology Flashcards
Typical pathology of pancreatic cancer
60% arise in head: obstruct CBD/early obstructive jaundice. 20% arise diffusely 15% arise in body 5% arise in tail Hard, stellate grey-White mass
Microscopic pathology of pancreatic carcinoma
Mostly adenocarcinoma from pancreas ducts. Moderately differentiated.
Adenoma-adenocarcinoma sequence (like colorectal)
precursor lesions= pancreatic intraepithelial neoplasias.
Adenocarcinoma: glandular spaces in fibrous stroma. Recapitulate normal ductal epithelia. Secrete mucin.
‘Desmoplastic response’ prominent: intense host rxn of fibroblasts and extracellular matrix.
Pancreatic cancer pattern of invasion/spread
Highly invasive
-local/peripancreatic: perineural infiltration, duodenal, CBD obstruction.
-lymph: peripancreatic, gastric, Mesenteric, omental, portohepatic nodes.
-vascular: to liver.
Metastases occasionally: lung, liver, bones.
Occasionally invade: spleen, adrenals, vertebral column, transverse colon, stomach.
Natural history of pancreatic cancer
Jaundice ~50% (usually painless)
- obstructive with painless non-palpable gallbladder (Courvoisier’s sign)
Non-specific:
- weight loss
- anorexia
- malaise
- pain is a late sign usually (chronic persistent epigastric, radiating to back)
Rarely:
- 10% migratory thrombophlebitis (trousseau’s sign)
- vomiting (duodenal obstruction)
- acute pancreatitis or diabetes mellitus.
Briefly symptomatic course rapidly progressive.
Management of pancreatic cancer
Conservative
Surgical
Early detection of pancreatic cancer
K-ras oncogene mutated in 90% but screening tests unproven.
Serum levels of CEA and CA19-9 usually elevated. Not specific or sensitive enough.
Endoscopic ultrasound AND per cutaneous needle biopsy for dialysis now.
Work up for Whipple’s resection
Triple phase CT C/A/P
EUS FNA (endoscopic ultrasound fine needle aspiration)
-> what is the mass, is it resectable?
Echocardiogram, lung function tests: is pt fit for surgery?
ERCP/MRCP/PET/Laparoscopy
Staging for pancreatic cancer
Whipple's T0/IS T1 2cm within pancreas T3 tumour outside pancreas but no major vascular involvement T4 major vascular involvement N0/1 M0/1
Non-resectable pancreatic cancer work up
- tissue diagnosis
- ERCP/PTC metal stents or bypass surgery
- pain relief
- palliative chemo
- induction into novel trials.
Prognosis post-Whipple’s
Pancreatic adenocarcinoma 20% 5y survival Cholangiocarcinoma 25% 5y survival Ampullary cancer 40% 5y survival Neuroendocrine 70% 5y survival Cystic lesions 70% 5y survival No resection 0% 5y survival
Peri-op mortality 1.4%
Causes of biliary strictures
Benign:
- iatrogenic, gallstones, pancreatitis, PSC, papillary stenosis
(Rarely: ischaemia, congenital, infective, autoimmune, choledochal varices)
Malignant: pancreas, ampulla, gallbladder, cholangiocarcinoma, intrahepatic.
Risk factors for pancreatic cancer
Smoking (2/3x) Diet rich in fats Chronic pancreatitis and DM Asn Inherited genetic syndromes 10% e.g. Hereditary pancreatitis, multiple endocrine neoplasia. Age: 60-80y (80%) M:F 2:1 3-5% cancer deaths uk 5y survival 5%
Advanced liver disease/cirrhosis changes
Nodular liver margin Segmental atrophy Heterogenous parenchyma Splenomegaly Porto-systemic shunts- varices, paraumbilical vein patency Abnormal portal vein flow Ascites
Complications of biliary calculi
Cholangitis Cholecystitis/Cholelithiasis Mucocoele of gallbladder Obstructive jaundice Ascending cholangitis Pancreatitis (transient Impaction at papilla) Gallstone ileus.
Causes of chronic live disease
Common: alcohol 60-70% NASH 10-15% viral hepatitis (B[D] and C) 10% Biliary disease 5-10% Primary Haemachromatosis 5%
Less common: autoimmune (PSC, PBC, AIH); metabolic (Wilson’s, a1AT deficiency).
Liver blood screen
Viral serology: HBcAb IgG, HBsAg; HVC Ab
Autoimmune serology: ASA, AMA, anti-LKM, immunoglobulin profile.
Metabolic profile: ferretin; caeruloplasmin; a1AT level.
Hepatitis B modes of transmission (6B) /risk groups (6H)
Modes of transmission: Bang (heterosexual sex) Bum (homosexual sex) Belushi (heroin/IV drug use/sharing needles) Blood (haemophiliacs/dialysis
Questions to ask if suspecting alcoholism?
Cut down? Have you ever felt the need to cut down on your drinking?
Annoyed? Have people annoyed you by criticising your drinking?
Guilty? Have you ever felt guilty about drinking?
EYe-opener? Have you ever felt you needed a drink first thing in the morning to steady your nerves/manage a hangover?
What is Mirrizzi’s syndrome?
Very large stone within the gallbladder externally compressing the CBD (in hartmann’s pouch or cystic duct)
What does AST, ALT, ALP and GGT show?
ALT and AST: hepatocellular death
ALP + GGT: cholestasis (>ALT and AST)
Causes of liver disease?
Viral, NAFLD, Alcohol, autoimmune, paracetamol OD, metabolic (haemachromatosis etc)
AST:ALT ratio >2 significance?
Alcoholic liver disease seems likely
But muscle inflammation in dermatopolymyositis may cause it
AST:ALT ratio <1 significance (if both are raised)
NAFLD, acute viral hepatitis, toxin hepatitis, ischaemic, chronic Hep C
Clinical biochemistry of paracetamol OD?
Decreased metabolic function: hypoglycaemia, metabolic acidosis
Decreased synthetic function: increased PT, low albumin
Other: hepatic encephalopathy
Cause of isolated rise in GGT?
Alcohol abuse (look for mild changes in AST or ALT; macrocytic RBC) Enzyme inducing drugs: phenytoin, carbamazepine, phenobarbital.
Antibodies associated with PBC?
Antimitochondrial antibodies
Antibodies associated with PSC?
ANA + pANCA +
Key differences of PBC and PSC
PBC: Autoimmune, Antimitochondrial Antibodies, Attenuated bile duct epithelium. Women. Asn with other autoimmune diseases. Affects small ducts
PSC: Periductal Onion skin fibrosis, and beaded appearance (O)on imaging. Men. Asn with UC. ANA+, pANCA+, antismooth muscle antibodies. Obliterative cholangitis. Affects big ducts. Oncology (asn with cholangiocarcinoma)
