Hepatobiliary Surgery JC064: A Large Liver: Liver Cancer

Question 1

***Hepatomegaly DDx

Answer 1

Malignant:
Primary
1. **HCC (most common)
2. **Cholangiocarcinoma
3. Others (e.g. Lymphoma)

***Secondary
1. GI tract
2. Other primary (Breast, Lung)

***Haematological
1. Lymphoma
2. Leukaemia
3. Myeloproliferative disease

Benign:
Benign tumours
1. **Haemangioma
2. **Adenoma
3. Focal nodular hyperplasia

Cyst
1. Simple cyst
2. ***Polycystic disease

Others
1. **Alcoholic cirrhosis
2. **Liver abscess

Question 2

History taking of Hepatomegaly

Answer 2

1. ***Pain (site, onset, duration)
2. ***Tea-colour urine (Jaundice)
3. N+V
4. Bowel changes
5. Systemic review: any symptoms suggestive of other primary malignancy
6. Constitutional symptoms: LOW, LOA, malaise
7. ***Past history of HBsAg carrier, Hep C, Liver disease
8. Social history: ***Alcohol
9. Family history of malignancy

Question 3

Physical examination of Hepatomegaly

Answer 3

General:
1. Pallor
2. **Jaundice
3. **Lymphadenopathy
4. ***Stigmata of chronic liver disease
5. Cachexia

Abdomen:
1. Hepatomegaly
- **size (cm below costal margin)
- tenderness
- **consistency (hard, firm, soft)
- **surface (nodular)
—> Smooth: Fatty liver, alcoholic cirrhosis, primary biliary cholangitis
—> Nodular: Polycystic kidney and liver disease
—> Large nodules: HCC
- edge
- **bruit (suggest vascular tumour e.g. HCC)
—> Vascular tumour (e.g. HCC) —> heard all over
—> Alcoholic hepatitis —> heard all over
—> Compression of aorta —> turn patient to right side and bruit less prominent

2. Other organomegaly
   - Splenomegaly: **Portal hypertension, **Haematological malignancy
3. Mass
4. ***Ascites
5. PR exam

Other systems

Question 4

***Characteristics of Hepatomegaly

Answer 4

Diffuse smooth firm Hepatomegaly:
- Alcoholic liver disease
- Haematological malignancies (∵ diffuse infiltrative process)

Irregular hard Hepatomegaly (likely to be solid tumours):
- HCC
- Cholangiocarcinoma
- Secondary malignancies

Question 5

***Investigations of Hepatomegaly

Answer 5

Blood tests
1. CBC
- e.g. **thrombocytopenia: ∵ hypersplenism in cirrhosis
- **abnormal WBC: haematological malignancies

2. Coagulation profile
   - e.g. ***prolonged INR in cirrhosis
3. LFT
   - clue to chronic hepatitis / cirrhosis
4. Viral hepatitis serology
   - **HBsAg
   - **Anti-HCV Ab
5. Tumour markers
   - **AFP: HCC, Embryonal carcinoma, Yolk sac tumour
   - **CEA: Cholangiocarcinoma, CRC
   - **CA 19.9: Cholangiocarcinoma, GI malignancies (e.g. **Pancreatic CA)
   —> Help but NOT diagnostic
   —> NOT all patients have ↑ tumour markers, mildly ↑ tumour markers can occur in benign conditions

Imaging
1. CXR (primary lung cancer, cannon ball lesions)

2. USG (**1st line)
   - whether a mass
   - confirm whether hepatomegaly
   - cirrhosis
   - **splenomegaly
   - tumours in pancreas
3. CT (***Contrast)
4. MRI
   - more phases, accuracies generally higher than CT
5. PET-CT
   - confirm primary tumour + detect metastasis in other organs

Endoscopy (for suspected primary GI malignancy)
1. Upper endoscopy
2. Colonoscopy

Biopsy
1. USG-guided percutaneous **FNAC
2. **Trucut core biopsy
- 1-2% bleeding risk
- 1-2% chance percutaneous needle tract seeding
—> **NOT advocate biopsy for all patients if well-established cancer + resectable (will do surgical resection + pathology instead)
—> only useful in patients with **advanced malignancy beyond surgery (chemotherapy + histopathology to establish nature)

Question 6

Management of Hepatomegaly

Answer 6

Depends on underlying pathology
- Surgical / Non-surgical

Question 7

Hepatocellular Carcinoma (HCC)

Answer 7

Causes:
1. ***HBV (80% of HCC)
2. HCV (common in japan, western)
3. Cirrhosis (Alcoholic and other types)
4. Alflatoxin (fungal derivatives, ↑ chance of HCC esp. in HBV carrier, in peanuts not probably stored, contaminated by mould)

3 pathological / macroscopic types:
1. Massive (i.e. big mass)
2. Diffuse (i.e. infiltrative)
3. Nodular (i.e. multiple small nodules)
4. Fibrolamellar HCC (very rare histological variant, in young females, in western mainly, good prognosis)

Pathology:
- **Rapid tumour growth (double size in 3-4 months)
- **Venous invasion tendency (portal vein / hepatic vein)
- **Intrahepatic metastasis to rest of liver (via **portal venous circulation)
- **Lung metastasis (via hepatic vein dissemination)
- **Peritoneal metastasis
- frequency association with cirrhosis (80% in HK)

Incidence:
- 1800 new cases per year
- commonest primary liver cancer
- 2rd commonest cancer deaths
- 5th commonest cancer incidence
- ***M:F = 4:1
- mostly >50 yo (but can occur in young patient)

Question 8

***Clinical features of HCC

Answer 8

1. Subclinical
   - liver relatively insensitive organ, large tumour can be asymptomatic, usually in HBV carrier who perform regular imaging surveillance —> incidental findings
   - screening with **AFP, **USG in HBsAg carrier / cirrhotic patients
2. RUQ / Epigastric pain
   - can be mistaken as peptic disease
3. Hepatomegaly
   - abnormal mass felt in upper abdomen
4. LOA, LOW, malaise
5. ***Decompensation of cirrhosis
   - Child-Pugh A suddenly develop ascites, variceal bleeding, hepatic encephalopathy
   - NB: HCC may also occur in patients without cirrhosis!
6. ***Tumour rupture
   - rare, intraperitoneal haemorrhage, acute abdominal pain, shock
7. Paraneoplastic features
   - rare, e.g. **polycythaemia, refractory diarrhoea, **fever of unknown origin, **hypercalcaemia, **hypoglycaemia

Question 9

***Diagnosis of HCC

Answer 9

One of cancers that no need histological diagnosis
1. ↑ AFP ***>400 ng/mL (quite specific)
- AFP normal (<20) in 30% HCC
- can be ↑ in chronic hepatitis / cirrhosis esp. with active viral replications (high HBV DNA in blood)

2. Imaging
   - USG

• CT scan (typical appearance)
  —> Non-contrast phase: hypodense
  —> Arterial phase / Contrast phase (1st 30 seconds, contrast still in arterial system): **hyperdense (tumour takes up blood mainly from hepatic artery instead of portal vein, on CT scan: compare with aorta (hyperdense aorta —> arterial phase))
  —> Portal venous phase: **hypodense (washout) (compared to parenchyma ∵ surrounding liver has more blood supply from portal vein)
  (NB: other cancers e.g. Cholangiocarcinoma / Secondary malignancy: arterial phase: ***hypodense instead (exact reverse))
• Post-Lipiodol CT (lipiodol injected via arteriography, repeat CT in 2 weeks for uptake by tumour, for uncertain cases after CT + Hepatic arteriography)
• MRI (alternative to CT, may also be useful in uncertain cases after CT)
• Hepatic arteriography (past, typical neovascularisation, for uncertain cases after CT)
• **PET scan (2 phases: **FDG + ***C-11 acetate) (FDG alone can miss HCC up to 50%)

3. Biopsy (only for inoperable cases / very uncertain imaging results)
   - FNAC
   - Trucut biopsy
4. Indocyanine (ICG) clearance test
   - a special dye excreted solely by liver
   - best test for ***liver function reserve if planning for surgical resection
   - ICG retention at 15 mins of <14% —> Adequate liver function

Question 10

***Surgical treatment of HCC

Answer 10

1. Hepatic resection
   - 20% HCC resectable
   —> **Unilobar
   —> **Absence of main portal vein invasion
   —> **Absence of distant metastasis
   —> **Adequate liver function (ICG retention at 15 mins of <14%)
   - 5 year survival rate >50%
   - operative mortality rate 1-5%
   - recurrence **50% (mainly in liver remnant due to **intrahepatic metastasis via portal vein / multicentric tumours, need regular 3-monthly surveillance with AFP, CT, early detection of recurrence —> re-resection / TOCE / ethanol injection)
2. Liver transplantation (one of few solid tumours that can be treated by transplantation)
   - HCC **<5-6.5cm (i.e. **Early HCC) (5cm: Milan criteria, 6.5cm: UCSF criteria)
   - **no macroscopic venous invasion / distant metastasis
   - **Child B/C cirrhosis (∵ may not be good candidate for surgery due to poor LFT)
   - 5-year survival rate 70-80%
   - immunosuppressants may ↑ recurrence chance, ∴ not for advanced cancers

Question 11

***Locoregional treatment of HCC

Answer 11

Embolisation
1. Transarterial oily chemoembolisation (TACE / TOCE) / Radioembolisation
- Local Chemotherapy + Embolisation
—> **Lipiodol (selectively taken up by HCC, unknown reasons)
+
—> **Cisplatin / Doxorubicin
+
—> **Gelfoam (block arterial supply of tumour —> slow down growth)
- bilobar / unilobar **unresectable tumours, reasonable liver function (bilirubin **<50), absence of main **portal vein thrombosis / distant metastasis
- **1st choice if **ruptured HCC (if still uncontrolled bleeding —> laparotomy)
- response rate: 30-40%
- continue once every 2-3 months

Ablation treatment (chemical / energy)
2. Percutaneous ethanol injection
- USG-guided for **<=3 tumours of **<=3-5 cm

3. Cryotherapy
4. Microwave / Radiofrequency thermoablation (**RFA)
   - for tumours **<5 cm, ***<4 nodules
   - outcome ~ surgical resection

Question 12

Non-surgical Palliative treatment

Answer 12

• for Metastasis to other organs
• Overall response rate: only 15-25%

1. Chemotherapy (e.g. doxorubicin), Tamoxifen, IFN
   - not proven to be effective (∵ HCC is a ***chemo-resistant cancer + poor LFT cannot tolerate chemo well)
2. External radiotherapy
   - stereotactic body radiation therapy (SBRT)
   - benefit limited for large tumours
3. Targeted therapy (***Sorafenib, Lenvatinib)
   - prolong survival by 3-4 months
4. ***Anti-PD1 immunotherapy (Nivolumab)
   - modulate immune cells to kill cancer cells
   - response ~20%

Question 13

Distribution of treatment in HCC

Answer 13

100 HCC patient:
- 20 Surgery
- 15 RFA
- <5 Liver transplantation (∵ only suitable for ***early HCC + scarce supply of organs)
- 20 TACE
- 35 Systemic treatment

Question 14

Long-term survival rate of HCC

Answer 14

5-year survival rate
- **Partial hepatectomy: 60%
- **Transplantation: 75%
- ***RFA: 50%
- TACE: 15%
- Systemic therapy: <5%

Advanced HCC with supportive treatment: 2-4 months

Question 15

Cholangiocarcinoma

Answer 15

• 5-20% of primary liver cancer
• ***Adenocarcinoma of bile duct
• > 50 yo

Causes:
- no exact known cause
- associated with
—> **HBV carrier
—> **RPC (common in chinese)
—> ***PSC
—> Ulcerative colitis (rare in chinese)

2 types:
- Intrahepatic Cholangiocarcinoma (~ HCC, present as a mass)
- Extrahepatic Cholangiocarcinoma (present as strictures —> **Jaundice)
—> **different presentation

Question 16

Clinical features of Cholangiocarcinoma

Answer 16

1. RUQ pain
2. ***Hepatomegaly
3. ***Jaundice (depend on location, e.g. near liver hilum)
4. LOA, LOW, fever

Question 17

Diagnosis of Cholangiocarcinoma

Answer 17

Tumour markers (may be ↑):
1. CEA (carcinoembryonic antigen)
2. CA 19.9

Imaging:
1. USG
2. CT
- hypodense in arterial phase (can be difficult to differentiate from secondary metastasis, must also do other imaging e.g. PET)
3. MRI
4. FDG-PET (no need dual tracer)
5. ***ERCP (can do stenting)

Biopsy (only for unresectable cases):
1. FNAC
2. Trucut

Question 18

Treatment of Cholangiocarcinoma

Answer 18

1. Surgical resection
   - treatment of choice
   - resectability 20%
   - **Bile duct excision + **Hepatectomy + ***Hilar LN clearance (important for staging) + Bile duct reconstruction
2. Palliative systemic chemotherapy (Cholangiocarcinoma ***more sensitive to chemo than HCC) + RT (for unresectable cases)
   - targeted therapy little role

Question 19

Metastatic cancer to Liver

Answer 19

• ***more common than primary liver cancer
• 2nd most common site of metastasis (lung most common)
• commonest site of metastasis for ***GI primary (∵ all blood supply from abdominal visceral organs go through portal vein through liver first)

Commonest site of Primary:
1. **Colon
2. **Stomach
3. **Pancreas
4. **Biliary tree

Other common sites of Primary:
1. Lung
2. Kidney
3. Breast
4. Gynaecological tract

Question 20

Clinical features of Metastatic cancer to Liver

Answer 20

1. Known primary with Hepatomegaly
2. Hepatomegaly / RUQ pain without symptoms referable to primary
3. Constitutional symptoms: LOA, LOW, cachexia
4. Ascites (suggest peritoneal seedling from GI / gynaecological primary)

Question 21

Diagnosis of Metastatic cancer to Liver

Answer 21

Tumour markers
1. CEA
2. CA 19.9

Imaging
1. USG
2. CT
3. MRI
4. PET

Biopsy (only for unresectable cases)
1. FNAC
2. Trucut
—> differentiate primary from secondary using ***immunostaining —> can tell origin

***Investigations for Primary
1. CXR (lung)
2. CT thorax (lung, breast)
3. Endoscopy (GI primary)

Question 22

Surgical treatment of Metastatic cancer to Liver

Answer 22

Hepatic resection
- **can be curative + prolong survival in patients with resectable **colorectal metastasis
- solitary / <=4 metastasis all within 1 lobe
—> 5-year survival 40%
—> 5-year disease-free survival 30%
—> 1/3 recurrence in liver remnant

• may be useful for palliation of symptoms from **carcinoid / **neuroendocrine tumours (∵ prolong survival + stop secretion of vasoactive peptides —> prevent symptoms e.g. flushing, diarrhoea)
• other metastasis suitable: **breast, **kidney, ***ovarian
• generally NOT indicated in metastasis from **pancreas, **lungs, ***stomach (∵ usually are widespread metastasis, very poor prognosis —> systemic chemotherapy instead)

Question 23

Non-surgical treatment of Metastatic cancer to Liver

Answer 23

1. Local ablative therapy e.g. ***RFA, SBRT
2. Chemotherapy
   - depends on response of type of tumour
   - systemic / transarterial with colorectal metastasis (response 20-30%)
3. Transarterial embolisation
   - generally not used for metastatic cancer except for ***neuroendocrine tumours which have good respond to TACE (for palliation)

Question 24

SpC Interactive tutorial: Advanced liver surgery for HBP malignancy

Answer 24

Screening for HCC:
1. HBV / HCV carriers
2. Cirrhosis
3. Family history of HCC

Methods:
1. USG
2. AFP, LFT
- every 6-12 months
- 90% detection rate

(HCC doubling time: 3 months)

Question 25

Evolution of HCC treatment

Answer 25

1. Open to Laparoscopic liver resection —> Early tumours: Minimally invasive approach
2. Improvement in open surgical techniques due to development of living donor liver transplantation —> Advanced tumours: Transplantation techniques, Complement resections

Question 26

Evolution of surgical techniques in liver transplantation

Answer 26

Resection techniques:
1. Anterior approach
2. Use of automatic vascular staplers
3. Use of energy device (Thunderbeat, Harmonic-ace)

Living donor liver transplantation techniques:
1. Control of IVC (isolate liver from IVC)
2. Venoplasty techniques (joining 2 veins together)
3. Haemodynamic control under IVC clamping without veno-venous bypass (important role by anaesthetist)
4. Parenchymal transection with patent inflow (living donor hepatectomy)
5. Understanding of small for size graft (i.e. partial graft) for recipient / remnant liver for donor

Question 27

2-stage hepatectomy

Answer 27

ALPPS: Associating Liver Partition and Portal vein Ligation for Staged hepatectomy

Indication
Major liver resection but ***insufficient future liver remnant (future liver remnant FLR <30%) (i.e. resection >= 3 Couinaud segments)

1. Ligate right portal vein —> allow blood shunted to left liver —> left liver hypertrophy (in 7 days)
2. Remove right liver

Question 28

SpC Interactive tutorial: HCC
Etiology of HCC

Answer 28

1. ***Hep B (80% of HCC in HK)
2. Hep C (predominant in Japan)
3. ***Cirrhosis
4. ***Aflatoxin (fungi: misstorage of food)

HBV
—(10 years if not cleared)—> Chronic hepatitis
—(20 years)—> Cirrhosis
—(20-30 years (Cirrhotic nodule —> Dysplastic nodule))—> HCC
or
HBV —> HCC

Epidemiology:
- Peak age: 50-70
- M»F

Question 29

Pathology of HCC

Answer 29

Macroscopic appearance:
1. **Massive type
- in **non-cirrhotic liver
- in **younger age group
- **large tumour with adjoining nodules
- variegated cut surface

2. **Nodular type
   - multiple greyish white, yellow / brown nodules in cirrhotic liver
   - follow sequence of regeneration nodules —> dysplastic nodules —> **cirrhosis
3. Diffuse type
   - least common
   - indistinguishable from cirrhosis
   - more associated with HCV pathway

Question 30

Spread of HCC

Answer 30

1. Local invasion
   - **Portal vein (Intrahepatic metastasis: spread to adjacent segment / contralateral lobe —> surgery resection need to resect all downstream liver segments)
   - **Hepatic vein
   - ***Bile duct
2. Lymphatic spread
   - 1/4 of patients
3. Transperitoneal spread
   - Rare
4. Haematogenous spread
   - Lung
   - Bone

Question 31

Clinical features of HCC

Answer 31

Tumour:
1. Subclinical (majority)
2. **Vague epigastric distension
3. Abdominal mass (usually 10cm before can be felt (stage T3: >5cm))
4. **Paraneoplastic syndrome
- Diarrhoea (vasoactive intestinal peptide)
- Hypoglycaemia (impaired gluconeogenesis)
- Hyperglycaemia (impaired glycogenesis)
- Hypercalcaemia (PTH-rP)
- Polycythaemia (Erythropoietin)
5. Weight loss

Cirrhosis:
6. **Ascites (∵ decompensated cirrhosis / occlusion of portal vein by tumour thrombus / external tumour compression)
7. **GI bleeding (variceal bleeding from cirrhosis portal hypertension, stress ulcer formation due to portal vein tumour thrombosis)

Complications:
8. **Secondaries in lung, bone (e.g. cough, bone pain, but usually detected by PET scan)
9. **Sharp pain due to bleeding (Tumour rupture)

Question 32

***HCC Treatment

Answer 32

Surgical treatment:
1. Partial hepatectomy
2. Liver transplantation (after total hepatectomy)

Locoregional treatment:
3. Local ablative therapy (RFA / Microwave) (realisable, predictable, repeatable) (still Curative intent)
4. Transarterial oily chemoembolisation (TACE) (2nd line)
5. Percutaneous intralesional alcohol injection (largely replaced by Local ablative therapy)

Question 33

Pre-op assessment / Investigations of HCC

Answer 33

1. Patient factor: **General status
   - Age (not a CI to surgery)
   - Concomitant medical disease
   - Hidden medical disease (e.g. CVS disease)
   —> **ECG, Spirometry, Astrup (ABG), Glucose, RFT etc.
   —> Aim to define whether the patient is fit for GA
2. Patient factor: **Liver function status
   - Clinical examination (signs of liver decompensation)
   - Liver biochemistry (Albumin, Bilirubin)
   - PT
   - Platelet
   - **Child-Pugh classification (anything beyond Child A —> risky for major liver resection)
   - ***ICG clearance test (>14% remaining after 15 mins —> cannot tolerate major liver resection)
   —> Aim to define whether liver function is sufficient for the patient to tolerate hepatectomy
3. Disease factor: ***Tumour status
   - USG (only for screening)
   - CT (provide better spatial resolution than MRI, ∵ short scanning time —> no need to hold breath)
   - MRI
   - +/- Hepatic arteriography (Angiography, obsolete, ∵ invasive, replaced by CT angiogram)
   - CXR (lung metastasis)
   - PET scan (FDG + C-11 acetate)
   —> Aim to define whether tumour still confined to one side of liver / whether technically feasible to resect / classify tumour, study anatomy before planning of surgery
4. Surgeon factor

Surgery (Laparoscopy / Laparotomy) can be done if:
1. General condition is good
2. Liver function is satisfactory
3. Tumour is confined to one lobe

Question 34

PET-CT

Answer 34

FDG:
- longer t1/2, easier to prepare
- good accuracy in CRC but poor sensitivity in HCC (∵ different cell type: well differentiated / moderately differentiated / poorly differentiated HCC —> only poorly differentiated is easily detected by FDG)

C-11 acetate:
- short t1/2 (~30 mins), harder to prepare
- high sensitivity

Question 35

***Staging of HCC

Answer 35

Stage 1: <2cm
Stage 2: 2-5cm
Stage 3: >5cm
Stage 4: Extrahepatic spread

Question 36

1. Partial hepatectomy

Answer 36

Indications:
1. **Unilobar involvement
2. **No invasion into IVC / Portal vein
3. Acceptable liver function for major hepatectomy
- **Child A
- **ICG retention 15 min <14%
4. No severe chronic medical illness

• Mortality rate 5%
• Morbidity rate 30%
• Hepatectomy can offer cure and is associated with a 5-year survival of 50%

Question 37

Sites of recurrence of HCC after hepatectomy

Answer 37

1. Liver remnant (80%)
2. Extra-hepatic (50%)
3. Both (5-10%)

Question 38

Laparoscopic liver resection

Answer 38

Now mainstream in small HCC
1. Pneumoperitoneum can compress on surface of hepatic vein —> less bleeding
2. New instruments for liver resection —> Clips and staplers
3. Laparoscopic CUSA
4. High definition monitor

Result:
- Less bleeding
- Comparable survival to open resection

Question 39

2. Liver transplantation

Answer 39

Treat both HCC + Cirrhosis at the same time

Indications:
1. Tumour <5cm single / <3cm up to 3 nodules (**Milan criteria)
2. **Child C cirrhosis

Question 40

3. Local ablative therapy (RFA / Microwave)

Answer 40

Indications:
1. **Tumour <5cm
2. Satisfactory liver function reserve
3. **CI to Laparoscopic / Open approach for HCC near to viscera

• Localised thermal treatment technique (Percutaneous / Open approach)
• RFA / Microwave (HIFU)
• Replacing Percutaneous intralesional alcohol injection
• Heating tumour cells to 45-50oC for >3 mins causes ***protein denaturation + irreversible cell damage
• Induces tumour destruction by heating tumour tissue to temp >60oC
  —> if up to ~70oC —> soot formation —> insulator of heat —> prevent dissipation of heat
  —> Cool-tip RF system using disposable electrodes (17G)
• USG / CT-guidance for introduction of electrodes + monitoring of ablation process

HIFU:
- ~Magnifying glass
- Oscillatory energy at focal point —> Coagulation necrosis
- USG energy transmitted through high density medium (e.g. water) —> patient put in waterbath

RFA vs HIFU:
- Similar effectiveness + survival benefit

RFA:
- Adhesion in subsequent operation
- Needle track
- ***CI in patients with ascites
- Ablation volume not as precise

HIFU:
- No adhesion in subsequent operation
- No needle track
- ***Favourable in patients with ascites
- Precise localisation, little collateral damage

Question 41

4. Transarterial oily chemoembolisation (TACE)

Answer 41

Purpose:
1. ***Palliative intention (TACE cannot kill all cancer cells)
2. Augment liver remnant for future hepatectomy

Indications:
1. **Bilobar involvement without distant spread, without complete portal vein obstruction / IVC involvement
2. **Unilobar involvement but liver function not acceptable for hepatectomy / RFA

Puncture femoral artery
—> Catheter into hepatic artery
—> Cisplatin + Lipiodol emulsion mixture to tumour (cell membrane of tumour absorb Lipiodol —> take in Cisplatin)
—> Block feeding vessel by Gelfoam (block blood supply —> ischaemia)

Complications (Felix Lai):
1. Post-embolisation syndrome (most common) (60-80%)
- Due to hepatocytes + tumour necrosis and ischemic damage to normal liver parenchyma
- Fever, N+V, abdominal pain, deranged LFT with ↑ AST/ALT (2:1) transiently for **1-2 days
- Full recovery is typically within 7-10 days
- Cover with antibiotics but should perform USG to exclude **liver abscess if symptoms persist for 1 week

2. **Liver failure (Hepatic decompensation) (most serious) (20-30%)
   - Treatment-induced ischemic damage to non-tumour bearing liver is responsible for precipitating or exacerbating liver failure
   - Usually reversible but it may be irreversible in 2% of cases
   - Clinically suspected by ↑ **bilirubin + ↑ ***PT (INR)
3. Ischaemic ulceration (due to disturbed GI blood supply)
   - Gastritis / Cholecystitis / Pancreatitis
   - ***Acalculous cholecystitis due to damage to the cholecystic artery

Question 42

5. Percutaneous intralesional alcohol injection

Answer 42

Indications:
1. **Tumour <3cm
2. **Tumour number <3

• Need to ***repeat 3-5 times before see effect
• Ethanol induce **dehydration + **coagulation necrosis of cancer cells —> fibrotic degeneration

Question 43

Systemic therapy

Answer 43

Previously used:
1. Chemotherapy (Doxorubicin)
2. Hormonal therapy (Tamoxifen, Octreotide)
3. Immunotherapy (IFN)
- None proven to give survival benefit

Current:
1. ***Sorafenib (Molecular targeting drug: RAF kinase + VEGF receptor)
- currently only approved drug for HCC
- prolong survival for 3 months in clinical trials

2. ***Anti-PD1 / PDL1
   - new in 2020

Question 44

Ruptured HCC management

Answer 44

Suspicion of HCC rupture (abdominal pain, pallor, history of Hep B/C, history of HCC, screening USG result)
—> Diagnosis of HCC rupture by **contrast CT
—> No ongoing blood loss —> **Conservative management
—> Ongoing blood loss
—> Haemodynamically unstable for TACE (TAE?) —> **Surgical intervention
—> Haemodynamically stable for TACE (TAE?)
—> **TACE (TAE?) —> Successful haemostasis —> Work-up for definitive treatment
—> Unsuccessful haemostasis —> ***Surgical intervention

Surgical intervention:
1. **Ligation of hepatic artery (associated with risk of liver failure) + Hepatectomy
2. **RFA in open approach (stop bleeding by coagulation + treat cancer) —> less risky in a shock patient + much better survival