JC64 (Surgery) - Hepatomegaly and Liver cancer

Question 1

Malignant Ddx of hepatomegaly

Answer 1

Primary liver tumour
Hepatocellular carcinoma (HCC, 85%)
Cholangiocarcinoma (CC)

Secondary tumours
Solid organ malignancies: GI, other primaries
Haematological: leukaemia, lymphoma

Question 2

Benign ddx of hepatomegaly

Answer 2

Infiltrative/replacement of parenchyma
Fat: alcoholic liver disease, NAFLD
Metabolic: Wilson’s disease, haemochromatosis, amyloidosis, other infiltrative diseases
Cysts: simple liver cysts, polycystic liver
Abscess: pyogenic, amoebic

Benign tumours:
Expansion of parenchyma
Hepatitis: infective, ischaemic, metabolic, autoimmune

‘Obstructive’
Vascular: Rt HF, TR, Budd-Chiari syndrome
Biliary: PBC, biliary atresia

Question 3

Outline brief history taking for hepatomegaly

Answer 3

 Pain: usually indicates significant enlargement stretching the liver capsule
 Jaundice ± obstructive jaundice
 GI symptoms, esp changes in bowel habits
 Constitutional symptoms and fever
 Systemic screen for any primary
 Hx and RFs for chronic liver disease
 FHx for malignancy

Question 4

Outline P/E for hepatomegaly

Answer 4

 General: cachexia, pallor, jaundice
 Cervical LNs
 Peripheral stigmata of chronic liver disease
 Hepatomegaly itself: upper and lower border, surface, edge, consistency, tenderness, bruit
 Other abd findings: splenomegaly, other masses, ascites
 PR exam for rectal masses

Question 5

Ddx diffuse smooth, firm hepatomegaly

Answer 5

Alcoholic liver disease

Haematological malignancies

Question 6

Ddx irregular, hard hepatomegaly

Answer 6

HCC
Cholangiocarcinoma
Secondary malignancies

Question 7

First-line investigations for hepatomegaly

Answer 7

□ Bloods: CBC, L/RFT, clotting profile, Viral hepatitis serology, tumour markers (AFP, CEA, CA19-9)***
□ Imaging: CXR, USG, triphasic CT, dynamic contrast MRI
□ Endoscopy: upper and lower (if suspicious for GI primaries)

□ Biopsy: plan for palliative radio-chemotherapy, defining cancer type for operability

• US-guided FNAC
• Tru-cut core biopsy

Question 8

Liver anatomy:

Arterial and venous supply

Portal hepatis structure

Answer 8

□ Blood supply: 80% from portal v., 20% from hepatic artery
□ Venous drainage via left, middle and right hepatic veins

□ Porta hepatis structures:
→ CBD: towards the Right
→ Hepatic Artery: towards the Left
→ Portal Vein: towards the Inferior side
→ Divides into left and right branches 2cm from liver

Question 9

Liver anatomy:

Ligaments and peritoneal reflections

Answer 9

→ Triangular ligament superiorly fixing superior surface of liver onto diaphragm

→ Falciform ligament anteriorly attaching anterior surface of liver onto abd wall

→ Ligamentum teres as remnant of umbilical v. running within falciform ligament to umbilicus

→ Ligamentum venosum as remnant of ductus venosus running along posterior surface of liver from lig. teres to IVC

→ Hepatoduodenal lig (lesser omentum) running from posteroinferior surface of liver to stomach, laterally bound by hilar vessels (f. of Winslow)

Question 10

List benign liver tumors

Answer 10

Hepatic Haemangioma

Hepatic Adenoma

Focal Nodular Hyperplasia (FNH)

Question 11

Hepatic Haemangioma /

Demographic
Pathogenesis
S/S
Complications

Answer 11

Demographic: Most common benign liver cancer, 30-50y, M:F ≈ 1:3

Pathogenesis: congenital vascular malformation, enlarge by ectasia (not hyperplastic), well-circumscribed lesion

S/S;

• Asymptomatic, incidental finding
• Vague RUQ discomfort/fullness: due to liver capsule stretch
• Mass effect: nausea, anorexia, early satiety
• Acute abd pain due to intra-tumour thrombosis/bleeding
• cutaneous haemangioma

Complications

• High output HF
• Hypothyroidism: ↑T3 deiodinase activity
• Kasabach-Merritt syndrome

Question 12

Hepatic haemangioma /

Dx investigations with typical findings
Mx

Answer 12

Dx:

• USG: well-demarcated, homogeneous, hyperechoic mass with high vascularity
• Triphasic CT
  Pre-contrast: well-demarcated hypodense lesion
  Early phase: characteristic peripheral nodular enhancement
  Delayed phase: remains enhancing
• MRI: smooth, well-demarcated homogenous mass

***FNAC: contraindicated! (risk of severe haemorrhage)***

Mx:
Observation for asymptomatic esp if small, eg. <1.5cm
Serial imaging for larger asymptomatic tumours >5cm
Surgical resection for symptomatic or complicated lesions
Non-surgical Tx: low dose RT, arterial embolization, IFN-α-2A if large, unresectable

Question 13

Hepatic Adenoma /

Demographic
Risk factors
Pathogenesis

Answer 13

Demographics: uncommon, usually in young women (M:F = 10:1)

RFs:
→ Strongly a/w oestrogen use (HRT/OCP
→ Anabolic androgen use
→ Others: glycogen storage diseases, genetic mutations, pregnancy

Pathology: benign proliferation of hepatocytes (NOT ‘hepatoma’), 70-80% solitary

Question 14

Hepatic adenoma /

S/S

Answer 14

□ Asymptomatic in majority
□ Episodic RUQ/epigastric pain due to hepatomegaly, bleeding or tumour necrosis
□ Spontaneous rupture + intra-abd bleed: sudden severe pain + hypotension
□ Abdominal mass or hepatomegaly
□ Malignant transformation: risk ~8-13%,

Question 15

Hepatic adenoma /

Dx investigations with typical results

Mx

Answer 15

Dx:
□ USG: non-specific well-demarcated hyperechoic SOL of liver
□ Triphasic CT: iso/hypodense (precontrast) → peripheral enhancement (early) → centripetal flow (portal venous) → iso/hypodense (late)
□ Others: MRI, 99mTc sulphur colloid scan, angiography

Mx:
□ Cessation of OCP + interval imaging for asymptomatic small adenomas
□ Surgical resection if symptomatic or >5cm
□ Avoid pregnancy/ undergo RFA before attempting pregnancy

Question 16

Focal Nodular Hyperplasia of liver /

Demographic
Pathogenesis
S/S
Dx and Mx

Answer 16

Question 17

HCC *

Demographics

Risk factors

Answer 17

Demographics: M:F = 3.3:1, mostly at age >50y (peak at 60s)

Chronic liver disease-related RF:
- Chronic hepatitis B (both cirrhotic and non-cirrhotic)
- α1-antitrypsin deficiency
- Cirrhosis:
Alcoholic
Metabolic: haemochromatosis, Wilson’s disease, NAFLD
Autoimmune: PBC, AIH, PSC
Viral: chronic hepatitis B, C

Non-alcoholic liver disease-related

• Aflatoxins: mycotoxins found in contaminated corn, soybeans, peanuts
• *- Smoking, alcoholism**
• *- Obesity and DM**
• Prior gallstone disease/cholecystectomy
• Diet

Question 18

HCC

Differentiate macroscopic vs microscopic subtypes
Biological behavior

Answer 18

Macroscopic types: massive (usu non-cirrhotic), nodular, diffuse (HCV-related)

Microscopic types:
→ Non-fibrolamellar type: vast majority, a/w HBV and cirrhosis
→ Fibrolamellar carcinoma (FLC): very rare (<1%)

Biological behaviour:
→ Very vascular tumour with high propensity for venous invasion (portal and hepatic vv)
→ Rapid tumour growth

Question 19

HCC

Routes of metastasis

Answer 19

Spread:
→ Transvenous (intrahepatic portal/hepatic vv. and bile ducts)

→ Lymphatic to intra-abdominal LNs (uncommon, 1-8%)

→ Haematogenous to lungs (most common), bones, adrenals (less common)

→ Transcoelomic to peritoneum (rare, but frequently missed on CT)

Question 20

Reasons for poor prognosis of HCC /

Answer 20

Majority have underlying cirrhosis (~80% for HBV, 100% for HCV)

Field cancerization: early or premalignant lesions present in other parts of liver

Asymptomatic in early stages: usually symptomatic only when tumour >8cm

Early intravenous spread: a/w early mets or portal vein thrombosis

Question 21

HCC *

Clinical presentation, S/S

Local, constitutional, paraneoplastic, metastatic

Answer 21

□ Asymptomatic (50%): usually by AFP/USG surveillance for Hep B or cirrhosis

□ Local:
→ RUQ/epigastric pain: vague, dull and persistent, capsular distension
→ Local mass effect: early satiety, N/V, palpable mass in upper abdomen
→ Obstructive jaundice
→ Decompensated cirrhosis: causes further deterioration of LFT
→ Tumour rupture (<3%): sudden onset of severe abd pain, generalized peritonitis and shock

□ Constitutional symptoms (80%): LOW, LOA, malaise, fever

□ Paraneoplastic syndrome:
→ HypoGly due to ↑metabolic needs
→ Erythrocytosis due to EPO secretion
→ Fever due to central tumour necrosis (reactive)
→ Others: hyperCa (PTHrP)

□ Metastatic: bone pain, dyspnoea

Question 22

HCC

Diagnostic investigations and typical findings

Serological (2)
Imaging (5)
Bx (1)

Answer 22

Elevated AFP >400ng/mL
Hepatitis serology: HBsAg, anti-HCV

Imaging:
- USG hepatobiliary system: >1cm, interval growth, hypoechoic mass

• Triphasic CT scan*****: Arterial phase: arterial enhancement, Portal venous phase: washout, Delayed phase: washout ± rim enhancement
• Dynamic contrast MRI: early arterial enhancement with rapid washout ± late rim enhancement
• Hepatic angiogram w/ lipiodol + post-lipiodol CT scan: dense staining due to neovascularization
• Dual tracer PET-CT with 11C-acetate and 18-FDG as tracers in uncertain cases
• *Liver biopsy by FNAC/trucut**
• for unresectable cases due to ↑risk of tumour tract seeding

Question 23

AFP for HCC diagnosis

Sensitivity and specificity
Function in HCC management
Confounding causes of elevation

Answer 23

400ng/mL (Sens <20%, Spec >95%) → almost diagnostic in high-risk individuals

Function:
Prognostic value: very high AFP predicts ↑tumour load, ↑aggressiveness, ↑risk of metastasis
Post-operative surveillance

• *Causes of ↑AFP:**
• Liver regeneration: HCC, acute/chronic viral hepatitis, cirrhosis
• Others: gonadal tumours (germ cell and non-germ cell), pregnancy, gastric CA

Question 24

List curative treatment options for HCC (3)

List palliative treatment options for HCC (5)

Answer 24

• *Curative:**
• *- Hepatectomy**
• *- Liver transplant**
• *- Local ablation:** radiofrequency ablation, microwave ablation, percutaneous ethanol ablation, cryoablation, HIFU
• *Palliative:**
• *- Embolization: Trans-arterial chemo-embolization (TACE), Trans-arterial radio-embolization (TARE)**
• Radiotherapy
• *- Targeted therapy (e.g. sorafenib)**
• Immunotherapy
• Supportive care

Question 25

Indications for Hepatectomy vs liver transplant vs local ablation for HCC

Answer 25

Hepatectomy: Resectable disease, with no vascular or extra-hepatic invasion, good reserve liver function

Liver transplant: Child C disease meeting Milan/UCSF criteria, Unresectable disease meeting transplant criteria

Local ablation: unresectable small and solitary (<5cm) or oligofocal tumours (<3 nodules <3cm)

Question 26

Indications for embolization vs radiotherapy vs targeted therapy vs immunotherapy for HCC Palliation

Answer 26

Embolization - 1st line for unresectable, large or multifocal HCCs with satisfactory liver fx and no Extrahepatic vascular invasion/metastasis (EVM)

Radiotherapy - after failure of other locoregional techniques if no EVM

Targeted therapy and Immunotherapy- 1st line for patients with EVM

Question 27

Cholangiocarcinoma - Check JC63

Question 28

Common primaries of secondary liver cancer

Answer 28

GIT primaries (MOST COMMON): Colon, stomach, pancreas, Biliary tree

Others: Lung, Kidney, Urogenital

Question 29

Treatment of metastatic liver cancer

Answer 29

• *Hepatic resection:**
• *-** Prolong survival in colorectal metastasis with neoadjuvant chemotherapy
• Palliation for carcinoid or neuroendocrine tumors with TACE/ TARE

Local ablation e.g. RFA

Other metastasis: resection/locoregional therapy usually has NO role

Question 30

Metastatic liver cancer

First-line investigations

Answer 30

Workup:
Tumour markers:
→ CEA/CA19-9: ↑ in some cases with primary GI malignancy (and CA lung if CEA)
→ AFP: for consideration of HCC

Triphasic CT scan:
→ Hypovascular mets (GI primary: colon, stomach, pancreas)
→ Hypervascular mets (neuroendocrine, RCC, breast, melanoma, thyroid)

Imaging the primary: CXR, CT, MRI, PET-CT

Liver Bx: FNAC/Trucut (usually only if unresectable)

Question 31

Why is DVT related to GI cancer

Answer 31

Cancer is a pro inflammatory state and pro-coagulation state

Tumour can obstruct lymphatic return and venous return causing stasis

Immobilisation