JC55 (Surgery) - Biliary obstruction, epigastric mass Flashcards
Physiology of bilirubin excretion
- Source
- Forms, solubility
Bilirubin: non-toxic breakdown product of heme
□ Formed in reticuloendothelial system (RES)
Two forms:
→ Unconjugated (indirect) bilirubin:
- Not water soluble → bound to plasma protein
- Cannot be excreted directly in urine
→ Conjugated (direct) bilirubin:
- Water soluble
- Can be excreted directly in urine
Describe the physiological processing of bilirubin in the liver
Hepatic handling:
□ Unconjugated bilirubin taken up by hepatocytes, transport from blood via Ligandin or Z protein
□ Bilirubin conjugated by UDP-glucuronyl transferase
□ Secreted into bile canaliculi into duodenum
Describe the enterohepatic circulation of bilirubin
Enterohepatic circulation:
□ Conjugated bilirubin reduced into urobilinogen by intestinal flora
10% reabsorbed into portal circulation into blood»_space;secreted in kidney as urobilin
□ Unabsorbed urobilinogen oxidized into stercobilinogen and then stercobilin
Clinical manifestations of cholestatic jaundice
□ Tea-coloured urine: excretion of conjugated bilirubin in urine (bilirubinuria)
□ Pale stools: reduced stercobilin content in stools
□ Pruritus: retention of bile acid in blood, deposition in skin
Differentiate features of pre-hepatic, hepatic and post-hepatic jaundice
Differentiate clinical features of pre-hepatic, hepatic and post-hepatic jaundice
Pre-hepatic:
- Lemon-yellow jaundice
- Dark stools (↑stercobilin)
- Normal urine
Hepatic:
- Yellow jaundice
- Normal stools
- Tea-coloured urine
Post-hepatic
- Greenish jaundice
- Pale stools
- Tea-coloured urine
- Pruritus ± scratch marks
Compare the LFT in pre-hepatic, hepatic and post-hepatic jaundice
Pre-hepatic:
- ↑unconj. bilirubin
- AST/ALT normal
- ALP/GGT normal
- Albumin normal
Hepatic:
- ↑conj. bilirubin
- ↑↑↑AST/ALT (AST>ALT = toxins) (ALT>AST = viral)
- ↑ALP/GGT
- ↓albumin (if subacute)
Post-heaptic
- ↑conj. Bilirubin
- ↑AST/ALT
- ↑↑↑ALP/GGT
- Albumin normal
Causes of pre-hepatic jaundice
Haemolytic anaemia - Congenital: Membrane (spherocytosis) Metabolic (G6PD) Hb (thalassaemia) - Acquired: Immune (auto-, allo-, drug-induced) Fragmentation (microangiopathic) Infection (parasitic, bacterial) Drugs and toxins
Congenital causes
- Gilbert syndrome
- Crigler-Najjar syndrome (very rare)
Causes of hepatic jaundice
Acute liver injury
- Viral hepatitis: A, B, E
- Alcoholic hepatitis
- Drug-induced hepatitis
- Autoimmune hepatitis
Chronic liver disease
- Viral hepatitis: B, C
- Alcoholic liver disease
- Non-alcoholic fatty liver disease
- Metabolic: Wilson’s disease, haemochromatosis, α1-antitrypsin deficiency
- Autoimmune: autoimmune hepatitis
- HCC
Congenital causes
- Dubin-Johnson syndrome
- Rotor syndrome
Causes of post-hepatic jaundice
Cholangitis/RPC
Choledocholithiasis
Malignant biliary obstruction (MBO)
Benign strictures
- Post-ERCP
- Stones, chronic pancreatitis
Other obstruction
- Mirizzi syndrome
- Choledochal cyst
- Biliary atresia
Medical causes
- PBC
- PSC
- Intrahepatic cholestasis
Causes of Malignant biliary obstruction
- Cholangiocarcinoma: hilar (Klatskin tumour), CBD
- LNs: HCC, gallbladder, lymphoma, stomach
- CA head of pancreas
- CA tail of pancreas with hilar LN spread
- CA ampulla or duodenum
Investigations for suspected pre-hepatic jaundice
CBC with reticulocyte
Peripheral blood smear
LDH, haptoglobin
Direct Coomb’s test
Thick and thin blood smear - Malaria
Investigations for suspected hepatic jaundice
Clotting profile
AFP
Hepatitis serology:
Acute: anti-HBc + anti-HAV IgM
Chronic: HBsAg, anti-HCV
Autoimmune panel:
ANA, anti-smooth muscle, anti-LKM1 (for autoimmune hepatitis)
Metabolic screen:
Cu: ceruloplasmin, 24h urine Cu
Fe: iron profile
Abdominal USG:
Cirrhosis, splenomegaly, ascites
Investigations for suspected post-hepatic jaundice
U/S of HBP
ERCP/MRCP if dilated biliary system
Contrast CT abdomen - MBO
Autoimmune panel ± liver biopsy if no dilated biliary system
- AMA for PBC
- p-ANCA for PSC (if segmental dilatation on ERCP)
Confounding causes of yellow skin
Other causes of yellow skin:
→ Diet: consumption of large quantity of food with lycopene or carotene
→ Drugs: rifampicin, quinacrine, TCMs
Outline history taking for hepatic causes of jaundice
□ Chronic liver disease: Hx of chronic liver disease and its complications
□ Alcoholic: Hx of alcohol abuse
□ (Metabolic)
□ Drugs: recent drug Hx, TCM intake
□ Autoimmune: Hx of autoimmune diseases
□ Virus:
→ Feco-oral (A/E): travel Hx, ingestion of seafood
→ Blood-borne (B/C): hep B/C status, FHx of hepatitis and HCC, blood transfusion, risk factors for blood-borne transmission (transfusion, IVDU, needle stick injury, MSM)
□ (HCC)
Outline history taking for post-hepatic jaundice
□ Cholangitis:
→ Charcot’s triad: jaundice, fever, RUQ pain
→ Reynold’s pentad: jaundice, fever, RUQ tenderness, hypotension, confusion
→ Past episode (recurrent pyogenic cholangitis)
□ Choledocholithiasis (CBD stone):
→ Episodic, painful jaundice in young individuals
→ Biliary colic symptoms: episodes of severe RUQ pain
→ Hx of gallstone diseases, past surgery, ERCP
□ Malignant biliary obstruction:
→ New onset, painless, progressive jaundice in old individuals
→ CA pancreas: constant, dull, boring epigastric pain radiating to back (usually late feature)
→ Constitutional symptoms: LOA, LOW, malaise
→ Metastatic symptoms: bone pain, dyspnoea, neck lump
□ Post-ERCP jaundice
Ddx epigastric mass + jaundice
D/dx of epigastric mass + jaundice can be:
□ Hepatomegaly (mild) due to biliary obstruction
□ Hepatomegaly due to metastasis or HCC
□ LN metastasis to coeliac axis and porta hepatis
□ CA stomach with metastatic LN in porta hepatis
□ Tumour obstructing both duodenum and bile duct → distended stomach + jaundice
Physical exam for jaundice
- General examination
General examination
□ Vitals: fever, haemodynamic stability
□ General inspection: jaundice, distension, ankle oedema
□ Specific signs: xanthomata (PBC), Kayser-Fleischer rings (Wilson’s disease), hyperpigmentation (haemochromatosis)
Physical exam for jaundice
- Abdominal exam and extra screening exams
Abdominal examination
□ Scars: previous HBP surgeries
□ Stigmata of chronic liver disease: ascites, caput medusae, gynaecomastia
□ Generalized distension: ascites can be due to malnutrition, peritoneal malignancy, malignant portal vein obstruction
□ Palpable masses:
→ Hepatomegaly: primary liver tumour, metastatic disease, biliary obstruction (usually mild)
→ Enlarged palpable gallbladder: indicates MBO if a/w painless jaundice
→ Splenomegaly: portal hypertension
Digital rectal examination for pale stools
Metastatic screen: LNs, bony tenderness, respiratory examination
Imaging modalities for obstructive jaundice
- Non-invasive
- Invasive
Non-invasive:
- Ultrasound
- CT
- MRI and cholangiopancreatography
- Positron emission tomography
Invasive:
- Endoscopic ultrasonography
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Percutaneous trans-hepatic cholangiography (PTC), Percutaneous transhepatic biliary drainage (PTBP)
Patient selection for MBO surgery
- Inoperability signs on P/E or imaging/ tumor factors contraindicated against surgery
P/E for any signs of inoperability
Left supraclavicular LNs (bx if uncertain)
Hepatomegaly with irregular surface
Sister Joseph’s nodule, ascites and rectal-vesical pouch deposits (Blumer’s shelf)
Imaging for any signs of inoperability
SMA, coeliac trunk encasement (i.e. encircling >1/2 of vessel circumference)
Liver, LN and peritoneal metastasis
SMV, portal vein, hepatic a. encasement
Patient selection for MBO surgery
- Patient factors
Assessment of patient fitness for surgery:
Age Hx of any known comorbidities Screening for unknown comorbidities Spirometry for lung function ECG Other lab tests, eg. RFT, blood glucose
Surgery for MBO
- Modalities of surgery
- Choice of surgery depending on following Patient factor and Tumor factors:
Poor patient factors
Poor tumor factors
Good patient and tumor factors
Good patient and tumor factors: Laparotomy + Bypass or Radical resection
→ Bypass if spread
→ Radial resection if confined
Poor tumor or patient factors: Palliative drainage by stents
→ ERCP/PTBD ± metallic stent (internal drainage)
→ Endoscopic stenting for GOO, Endoprosthesis
Aim of radical resection of MBO
Remove:
- Tumor and part of organ or origin
- Regional LN dissection
- Tumor-free resection margin
Compare Endoprosthesis stenting vs PTBD vs Surgical bypass for MBO
Endoprosthesis Stent: Preferred**
- Lower initial morbidity and mortality
- Relieve obstruction and strictures
- More late biliary complications
- More re-interventions
PTBD:
- Indicated in Periampullary diverticulum, tumor strictures too severe for endoscopes, hilar tumors
Surgical bypass:
- Higher early morbidity, longer hospital stay
- Better long-term results
Palliative treatments for MBO
- Unresectable tumor after laparotomy
- Unresectable tumor found pre-operatively
- Advanced, inoperative stage
Palliative options: usually non-operative means to relief obstruction
- Unresectable tumor after laparotomy: bypass surgery
- Definite unresectable tumor pre-operatively: Endoscopic biliary stenting or PTBD
- Palliative chemotherapy: Must clear biliary obstruction to improve liver function beforehand
Ddx intra-hepatic causes of Obstructive jaundice
Hepatocyte dysfunction (hepatitis, end-stage liver disease)
Drugs: anabolic steroids, OC pills, chlorpromazine, arsenic
Primary biliary cholangitis (A/I destruction of small ducts)
No enteric intake (TPN, post-operative) (↓CCK secretion → ↓GB contraction)
Intrahepatic cholestasis of pregnancy (a/w ↑oestrogen levels)
Ddx extra-hepatic causes of Obstructive jaundice
- Intraluminal
- Mural
- Extramural
Intraluminal
CBD stones
Cholangitis (or RPC)
Parasitic (eg. Ascaris lumbricoides, liver flukes)
Tumour thrombus (rare, in HCC) or haemobilia (v. rare)
Mural
Benign strictures: post-instrumentation, gallstones, chronic pancreatitis
Primary sclerosing cholangitis
Sphincter of Oddi dysfunction (intermittent)
Cholangiocarcinoma below hilum
Extramural
Gallbladder stone in Mirizzi syndrome
Acute and chronic pancreatitis (uncommon)
Carcinoma of head of pancreas
Carcinoma of Ampulla of Vater or duodenum152
Porta hepatis LN
Define Courvoisier’s law in MBO
Presence of palpable gallbladder in a patient with painless obstructive jaundice is unlikely to be due to stone disease.
Reason: a gallbladder that gives rise to CBD stone is likely to have been chronically inflamed leading to fibrosis and therefore would not be palpable
Tumor markers for MBO
Limitations of each marker
Tumour markers: limited utility in acute setting
→ CA19-9 for CA pancreas, cholangiocarcinoma (and GI cancers)
→ CEA for adenocarcinoma
→ AFP for HCC (>400 diagnostic of HCC)
Limitations:
CA19-9 is excreted via bile therefore invariably ↑ in any cholestasis. Measure CA19-9 after relief of obstruction.
CEA is highly non-specific, little role in initial diagnosis. Measure pre-operatively.
AFP is rarely useful as HCC is rarely the cause of MBO
Management plan for suspected MBO
Management of biliary sepsis as first priority
- Delineate cause and level of obstruction by imaging or cholangiography
- Early drainage for: Biliary sepsis or stones, Poor liver function due to prolonged cholestasis, Klatskin tumor
Assess resectability: tumour factor, patient factor, liver factor
Definitive or palliative management based on resectability
Sequence of imaging for MBO
- Which modality for screening
- Which modality is first line
- Which modalities for confirmation of malignancy, staging and biopsy
Trans-abdominal ultrasound of hepatobiliary system (US HBS)
→ As first-line to confirm extrahepatic cholestasis (vs intrahepatic)
Direct cholangiography: gold standard, by
→ Endoscopic retrograde cholangiopancreatography (ERCP)
→ Percutaneous transhepatic cholangiography (PTC) if ERCP C/I
→ MR cholangiopancreatography (MRCP) if intervention is not required
If malignancy present/likely, then can consider
→ Triphasic CT scan for diagnosis ± staging
→ Endoscopic US (EUS) for diagnosis, staging and Bx
→ ± PET-CT for staging
Goals of imaging MBO
(1) Extrahepatic vs intrahepatic cholestasis
(2) Level of obstruction
(3) Identify exact cause
(4) Staging of cancer
Ultrasound of hepatobiliary system/ Endoscopic ultrasound (EUS)
- Functions
- Disadvantages
Functions:
- dilated biliary system indicate level of obstruction
- Mass in pancreas, bile duct and gall-bladder
- Vascular and LN involvement
- FNA of lesion
Disadvantages:
unable to visualize primary tumour and distal biliary system (CBD, ampulla, pancreas obscured behind D2)
Operator dependent
CT abdomen with pancrease protocol
- Phases of scan and structures observed
Pancreatic protocol: best visualizes pancreatic lesions
→ Oral water contrast to improve image quality + ↓artefacts
→ Early arterial phase (25s) to visualize aorta/SMA invasion → if enhancing, then more likely to be neuroendocrine tumour
→ Pancreatic phase (40s) to visualize parenchymal lesions
→ Delayed phase (70s) to visualize liver secondaries
Typical findings of following pathologies on HBP ultrasound
- Choledocholithiasis
- Gallstone disease
- Cholangitis
→ Choledocholithiasis: dilated CBD (>6mm), CBD stone
→ Gallstone disease: GB stone/sludge, thickened GB wall, pericholecystic oedema, stranding (if cholecystitis)
→ Cholangitis: thickened CBD wall
Ddx the following findings on CT abdomen for MBO
Double duct signs
Ductal dilatation
Hypoenhancing pancreatic mass
Hypovascular liver mass
→ Double duct sign indicates CA ampulla or head of pancreas
→ Ductal dilatation (>6mm): when not a/w stones, likely indicates malignant strictures
→ Hypoenhancing pancreatic mass in CA pancreas
→ Hypovascular liver mass in liver secondaries
Phases of abdominal contrast CT
Structures highlighted in each phase
Non-contrast: for baseline anatomy
Early arterial/angiogram phase (15-20s): only show arteries not organs
(Late) arterial phase (35-40s): enhancement in arterially supplied organs (eg. pancreas)
(Late) portal/hepatic phase (50-60s): enhancement in portal venous supplied structures (eg, liver parenchyma)
Nephrogenic phase (100s): homogenous enhancement of kidney parenchyma
Delayed phase (>5min): wash out of contrast in most structures except fibrotic structures and urinary tract
Cholangiography
- Function
- Forms
Cholangiography: diagnostic (visualize obstruction) and therapeutic (drain obstruction)
□ Percutaneous transhepatic biliary drainage (PTBD)
□ Endoscopic retrograde cholangiopancreatography (ERCP)
□ Magnetic resonance cholangiopancreatography (MRCP) if intervention is not needed
ERCP
- Indicated pathologies
Obstructive jaundice for workup
Suspected CBD stone (not for others)
Suspected biliary pancreatitis (not for others)
Suspected periductal malignancies (extrahepatic cholangioCA, CA HOP, CA ampulla)
Suspected sphincter of Oddi dysfunction
Suspected biliary strictures and RPC
ERCP
- Therapeutic procedures
- C/I
Endoscopic sphincterotomy
Stent insertion and removal (over guidewire)
Dilatation of strictures (by balloon)
Retrieval of stones (by basket or balloon)
Brush biopsy (Sens ~60% only)
Snare ampullary resection in CA ampulla (not curative)
C/I: OGD contraindications (eg. aspiration risk, suspected perforation), previous gastric resection
Complications of ERCP (5)
Sedation-related: hypoxaemia/resp suppression, hypotension, arrhythmias, tachycardia (a/w buscopan)
Endoscopy-related: hypercapnia (due to CO2 insufflation), perforation
Pancreatitis (3-4%): most common
- mechanical injury from instrumentation of pancreatic duct, hydrostatic injury from contrast injection
Ascending biliary infections (1-2%)
- Ascending cholangitis (1.4%): failure in complete drainage
- Acute cholecystitis (≤0.5%): introduction of contaminated contrast into a poorly emptying GB
GI bleeding (1-2%) due to sphincterotomy
Percutaneous transhepatic cholangiography or biliary drainage (PTC, PTBD)
- Indications
Indication: usually when ERCP is not possible/too risky
→ Distorted anatomy rendering ERCP impossible (eg. previous hepatobiliary reconstruction, Klatskin tumour)
→ Inaccessible papilla in CA ampulla, duodenal obstruction
→ Distal complete obstruction, eg. advanced cholangioCA (ERCP impossible)
→ High-risk patients (ERCP is generally a/w ↑risks, but is less painful)
Complications of PTC/ PTBD
→ Bacteremia and sepsis due to liver puncture
→ Severe haemobilia (0.2-4%) if puncture artery
→ Biliary peritonitis due to dislodgement of PTBD
→ Bleeding due to puncture into liver vessels
→ Dislodgement: very common!
MRCP
- Indication
- Advantages
- Disadvantages
Indication:
- non-invasive, useful when intervention is not needed (diagnostic only, usu when the suspicion for malignancy is not high) and
- contrast injection is C/I
Advantage:
- no contrast required (suitable for contrast allergy),
- non-invasive (little morbidity),
- allow evaluation of ducts above + below stricture,
- identify any intrahepatic mass lesions
Disadvantage:
- motion artifacts, image artifacts (fluid in duodenum/diverticula),
- lower resolution (can miss smaller lesions)
PET scan for MBO
- Functions
- Differentiate cancer and inflammation
- Identify LN or distant metastasis
- Perioperative staging and selection for laparotomy
Laparotomy approach for MBO
- Function
- List subtypes of radical resection and bypass procedures
Function: Intraoperative assessment of resectability
Radical resection if tumour is confined
1. Whipple for CA pancreas, distal CBD cholangioCA, CA duodenum, CA ampulla
2. Radical cholecystectomy for CA gallbladder
3. Major hepatectomy + caudate lobectomy + resection of confluence of hepatic ducts for
Klatskin tumor
Palliative bypass if tumour has spread
- Single bypass: choledochojejunostomy or hepaticojejunostomy to Relieve biliary obstruction
- Double bypass: CJ/HJ + gastrojejunostomy to Relieve biliary + duodenal obstruction
- Triple bypass: CJ/HJ + GJ + pancreaticojejunostomy to Relieve biliary + duodenal + pancreatic obstruction
Reasons for high post-operative mortality of MBO surgery
Pathophysiological effects of MBO:
- Poor clotting factor synthesis»_space; high bleeding risk, poor wound and anastomosis healing
- Poor protein synthesis, gluconeogenesis and ketogenesis»_space; cancer cachexia and malnutrition
- Poor RES and cell-mediated immunity»_space; endotoxemia and biliary infections
- Hepato-renal failure
- Bleeding gastric erosion/ ulcers
Measures to reduce complications of MBO surgery
- Nutritional support for cancer cachexia and poor liver function
- Vitamin K support + FFP infusion for poor clotting
- Antibiotics coverage for poor cell-mediated immunity and biliary infections
- Mannitol, dopamine for renal failure prevention
- H2 antagonist - alleviate gastric ulcer
