hepatocellular carcinoma, cholangiocarcinoma, hepatectomy, liver cancer

1. DISCUSS RECENT ADVANCES
IN THE MANAGEMENT OF
LIVER CANCERS
Presenter: DR BASHIR BIN YUNUS
Moderator: PROF KHALID LAWAL

2. OUTLINE• INTRODUCTION
• EPIDEMIOLOGY AND RISK FACTORS
• CLASSIFICATION
• MANAGEMENT
• HISTORY
• EXAMIMINATION
• INVESTIGATION
• TREATMENT
• SURGERY
• ABLATION TECHNIQUE
• REGIONAL LIVER THERAPIES
• RADIATION
• CHEMOTHERAPY
• PROGNOSIS
• FUTURE TRENDS
• CONCLUSION

3. INTRODUCTION
• Liver cancers may arise from the hepatocytes, bile duct epithelium,
and the endothelial cells within the liver.
• They represent the most common solid organ cancers worldwide,
with hepatocellular carcinoma (HCC) being the commonest primary
liver malignancies.
• However, secondaries to the liver are the commonest malignant liver
tumours (primary: secondary 1:20) with colorectal forming bulk of
majority.
• They present diagnostic and therapeutic challenges.
• In the last 2 decades, recent advances in the management has
reduced morbidity and mortality, with improved survival rate.

4. • HCC is the 5th most common malignancy worldwide with an estimate
of 750,000 new cases diagnosed annually.
• Incidence increase with age with 4-8 times commoner in males than
females.
• Its geographical distribution closely mirrors that of viral hepatitis.
• It is common in Mozambique, South East Asia, tropical Africa, Taiwan.
In Mozambique it is seen in younger age group below 30 years.
• Cholangiocarcinoma is disease of the elderly and peaks at the eight
decade of life. Its usually more fatal and death result from hepatic
failure and biliary sepsis in the year of diagnosis.

5. ANATOMY

6. RISK FACTORS
• Infection;
• Hepatitis B virus,
• Hepatitis C virus
• Cirrhosis;
• Laennec’s (alcohol-induced),
• Autoimmune hepatitis,
• Primary biliary cirrhosis
• Environmental;
• Aflatoxins,
• N -nitrosylated compounds,
• Pyrrolizidine alkaloids,
• Thorotrast
• Metabolic disorders;
• Alpha1-antitrypsin deficiency, Citrullinemia
• Familial cholestatic cirrhosis
• Galactosemia
• Hemochromatosis
• Hereditary tyrosinemia
• Porphyria cutanea tarda
• Type 1 and 3 glycogen storage disease
• Wilson’s disease
• Chronic biliary inflammation (risk for
cholangiocarcinoma)
• primary sclerosing cholangitis,
• choledochal cysts,
• chronic biliary infections.

7. • NB;
• Western world – alcohol induce
• Tropical countries – hepatitis and aflatoxins
• Aflatoxins produced by the fungi Aspergillus flavus and Aspergillus
parasiticus have also been linked to HCC. These are fungi that grow
on grains, peanuts, and other food products, and are the most
common cause of food spoilage in the tropics. These fungi produce
aflatoxins designated B 1 , B 2 , G 1 , and G 2 . Aflatoxin B 1 is the
most hepatotoxic, and chronic exposure to these mycotoxins can
promote HCC.

8. CLASSIFICATION
• A. PRIMARY – originates from the liver
• Hepatocellular carcinoma (80%)
• Cholangiocarcinoma (20%)
• others
• Gallbladder cancer
• Hepatoblastomas in infant and children
• B. SECONDARY- metastatic from extrahepatic primary sites
• Metastatic colorectal cancer
• Neuroendocrine tumours
• Others
• Intra-abdominal or extra-abdominal

9. • Cholangiocarcinoma
• Could be intrahepatic (peripheral) or extrahepatic (central). The proximal
extrahepatic tumours at the confluence of the right and left hepatic duct
present with painless jaundice rather than the features of the tumour. -hilar
tumours (Klaskin tumours). The extrahepatic are commoner. Distal has better
prognosis due to resectability.
• Gallbladder cancer is a rare aggressive tumor with a very poor
prognosis. Over 90% of patients have associated cholelithiasis.

10. MANAGEMENT
• HISTORY
• NB; they are slow growing and usually present at an advance stage due
to relatively hidden location of the liver hence reaching a large size
before being palpable, large functional reserve of the liver, small tumours
are usually asymptomatic and are discovered as incidental findings.
• Right hypochondrium mass – painless, may be dull aching and vague
radiate to the shoulder
• Jaundice – hepatic dysfunction commonly or compression
• Weight loss, anorexia, nausea, and lethargy.
• Fever, may result from central necrosis of large tumours
• GI bleeding 10%
• Hypoglycemia 1%- paraneoplastic syndromes or impairment.

11. PHYSICAL EXAMINATION
• Chronically ill-looking, jaundiced, may have features of
encephalopathy, stigmatas of chronic liver disease.
• Liver is enlarged, hard and irregular, nodular due to accompanying
cirrhosis, hepatic thrill and bruit in 25%
• Ascites in 40% often massive, splenomegaly and features of portal
hypertension
• Features of acute presentation when the tumour undergo a
spontaneous rupture with hemoperitoneum; guarding, rebound
tenderness and ileus.
• NB; For metastatic cancers, features of the primary malignancy is
sort for.

12. INVESTIGATIONS
• AIMS :
• Verification of diagnosis
• Determine the extent of disease
• Estimate the functional liver reserve

13. VERIFICATION OF DIAGNOSIS
• Imaging
• USS; hyperechoic mass, mosaic pattern with thin halo and lateral shadows.
• Contrast enhanced CT scan; triple phase.
 Hypodense, mosaic, vascular lesion with irregular margin.
Size, location, extent, vascularity, portal vein invasion, nodal status, portal vein
thrombosis
Operability
• MRI
• Laboratory
• Serum AFP > 500ng/dL (NB; in cholangiocarcinoma AFP is normal)
• HBsAg HCV
• Percutaneous biopsy (debatable due high yield of non-invasive above
and possible complications from the procedure)
Space occupying lesion with non-diagnostic AFP
Portal vein biopsy to exclude surgery or transplant, in case of portal vein
involment

14. Extent of disease evaluation
• A
Whether the disease is isolated in the liver
Whether the distribution within the liver is amenable to surgical resection
• CT Scan;
May show hanging type, pushing type, or infiltrating /invading type
• Celiac angiography/ CT angiography /doppler USS
• B
Distant metastesis
CXR
Bone scan
PETscan

15. DETERMINATION OF FUNCTIONAL RESERVE

16. • Functionally, well compensated cirrhosis ; Childs A
• Decompensating Child’s B
• Decompensated Child’s C
• Generally, partial hepatectomy is offered to only Child’s A and the
most favorable B.
• In general, class C patients are only offered supportive care, since
even nonsurgical ablative methods is associated with mortality in a
third of patient.

17. • NB; other investigations
• LFT
• PET SCAN
• FBC
• U/Ecr
• GXM

18. TREATMENT
HEPATIC RESECTION
• Gold standard and treatment of choice, remains the real option for
cure.
• Removal of 80% of liver is compatible with life
• Laparoscopic resection is becoming popular
• Treatment is for noncirrhotic patient with Class A or favorable B
• Operative mortalities in most major centers is <5%
• Has a 5 year survival of about 40%
• In the recent years, at high volume centers, cirrhotic liver are resected
with a mortality of 10% or more with a 5 year survival of 30%, this is
achieve following careful patient selection.

19. • The use of intraoperative ultrasound has led to virtually “bloodless”
liver surgery in the modern era. Intraoperative ultrasound is done to;
• Identify tumour
• Recognizing the anatomy
• Unexpected contralateral tumour
• Intrahepatic selective vascular control using a balloon catheter
• Guided biopsy
• The innovation of technology have expanded the list of liver
parenchymal transection devices and hemostatic agents
• Modern anesthesia with reduction of intra-operative and monitoring
of CVP has significantly reduce bleeding complications.

20. Techniques of parenchymal dissection
• CUSA- cavitron ultrasonic surgical aspirator
• Ultrasonic dissector stapler
• Bipolar vessel sealer
• Water jet dissector
• Blunt fracture and clip
• Harmonic scalpel, autosonix ultrasound
• Endovascular staplers
• Topical agent (fibrin glues, surgicel, Gelfoam, Avitene, Tisseel, Floseal,
Crosseal).

21. Nomenclature
• BRISBANE 2000 LIVER TERMINOLOGY
• Rt hemihepatectomy V, VI, VII, VIII
• Rt trisectionectomy IV, V, VI, VI,VII,VIII
• Lt hemihepatectomy II, III, IV
• Lt lateral sectionectomy II, III
• Lt trisectioncetomy II,III, IV, V, VIII
• Right posterior sectionectomy VI, VII
• Caudate lobectomy I

22. Transplant
• In cirrhotic patients with HCC, total hepatectomy with orthotopic liver
transplantation is required
• Indications
• Patients who are not candidates for resection
• Tumours less or equal to 5cm
• Tumours less than 3 in number
• Tumours without portal or hepatic vein invasion
• Tumors without extrahepatic spread

23. Milan criteria
• One lesion smaller than 5cm
• Up to 3 lesions, each smaller than 3cm
• No extrahepatic manifestations
• No evidence of gross vascular invasion

24. Other surgeries
• Non anatomical resection;
• For metastatic not involving major vessel and in a peripheral location
• Debulking in staged hepatectomy
• NB; contraindications to resection of hepatic colorectal metastatic
• Extrahepatic spread
• Nodal involvement along with primary
• Short disease free interval less than 1 year
• ≥ 4 secondaries
• Secondary > 5cm
• Bilobar spread
• CEA> 200ng/dL

25. Non operative techniques
• ABLATION TECHNIQUE
• Radiofrequency ablation
• Ethanol ablation
• Cryoabation
• Microwave
• REGIONAL LIVER THERAPIES
• Chemoembolization ; lipiodol, doxorubicin,
• Hepatic artery pump chemoperfusion; floxuridine
• Internal radiation therapy (yttrium-90 internal radiation) – Injected into hepatic artery
• EXTERNAL BEAM RADIATION
• Stereotactic radiosurgery (CyberKnife, Trilogy, Synergy)
• Intensity-modulated radiation therapy
• SYSTEMIC CHEMOTHERAPY/IMMUNOTHERAPY
• Not effective
• Sorafenib – tyrosine kinase inhibitor (VEGF, PDGF). Inhibits tumor angiogenesis
• Bevacizumab combine with gemcitabine, cisplatin
• INTERFERON and chemotherapy (PIAF)- Platinum,interferon,adramycin,fluorouracil
• Nivolumab
• Indications
• Neoadjuvant therapy
• Palliative care for unresectable lesions

26. Prognosis
• Overall prognosis is poor, with a 5 year relative survival rate of 18%.
• The length of survival largely depends on the extent of cirrhosis of the
liver, cirrhotic patient have shorter survival and limited therapeutic
options.
• Portal vein occlusion shortens survival

27. Current trends
• Preoperative portal vein embolization
• Staged hepatectomy
• Laparoscopic liver resection

28. Screening
• Hepatitis B, C
• AFP
• Imaging

29. Prevention
• Primary –
• vaccination; hepatitis B,C
• Decrease alcohol use
• Safe blood transfusion
• Safe sex
• Secondary
• Early detection and treatment of hepatitis
• Control of aspegillus flavus and parasiticus

30. Follow up
• Imaging 2-3monthly
• LFT, AFP monthly

31. References
• Schwartz
• Maingot
• Medscape
• SRB